Next Article in Journal
The Mitochondrial Genome of a Plant Fungal Pathogen Pseudocercospora fijiensis (Mycosphaerellaceae), Comparative Analysis and Diversification Times of the Sigatoka Disease Complex Using Fossil Calibrated Phylogenies
Previous Article in Journal
Atheroprotective Properties of Costus spicatus (Jacq.) Sw. in Female Rats
 
 
Search for Articles:
Title / Keyword
Author / Affiliation / Email
Journal
Article Type
 
 
Advanced Search
 
Section
Special Issue
Volume
Issue
Number
Page
 
Journals
Life
Volume 11
Issue 3
10.3390/life11030213
life-logo
Submit to this Journal Review for this Journal Propose a Special Issue
► Article Menu

Article Menu

share Share announcement Help format_quote Cite question_answer Discuss in SciProfiles thumb_up
...
Endorse textsms
...
Comment
first_page
settings
Order Article Reprints
Font Type:
Arial Georgia Verdana
Font Size:
Aa Aa Aa
Line Spacing:
Column Width:
Background:
Review

Exogenous Factors Affecting the Functional Integrity of Male Reproduction

by
Filip Tirpák
1,*,
Hana Greifová
2,
Norbert Lukáč
2,
Robert Stawarz
3 and
Peter Massányi
2,3,*
1
AgroBioTech Research Centre, Slovak University of Agriculture in Nitra, Tr. A. Hlinku 2, 949 76 Nitra, Slovakia
2
Department of Animal Physiology, Slovak University of Agriculture in Nitra, Tr. A. Hlinku 2, 949 76 Nitra, Slovakia
3
Institute of Biology, Pedagogical University of Krakow, Podchorazych 2, 30-084 Krakow, Poland
*
Authors to whom correspondence should be addressed.
Life 2021, 11(3), 213; https://doi.org/10.3390/life11030213
Submission received: 1 February 2021 / Revised: 4 March 2021 / Accepted: 7 March 2021 / Published: 9 March 2021
(This article belongs to the Special Issue Animal Cell Systems: Response to Exogenous Factors)
Versions Notes

Abstract

:
Natural processes along with increased industrial production and the irresponsible behavior of mankind have resulted in environmental pollution. Environmental pollutants can be categorized based on their characteristics and appearance into the following groups: physical, biological, and chemical. Every single one of them represents a serious threat to the male reproductive tract despite the different modes of action. Male gonads and gametes are especially vulnerable to the effect of exogenous factors; therefore, they are considered a reliable indicator of environmental pollution. The impact of xenobiotics or radiation leads to an irreversible impairment of fertility displayed by histological changes, modulated androgen production, or compromised spermatozoa (or germ cells) quality. The present article reviews the exogenous threats, male reproductive system, the mode of action, and overall impact on the reproductive health of humans and animals.

1. Introduction

The present society is largely focused on the creation and optimization of technological methods. This effort for financial or personalistic gain, or the process simplification of production brings along high, although on first sight, imperceptible sacrifice. The development and spread of diseases of affluence reflect the negative impact of various byproducts of industrial production or other anthropogenic activities. Accordingly, the most advanced industrial areas are usually also known for the enormous environmental pollution. The accumulation and consecutive synergism of toxicants in the living environment leads to impairment of individual physiological processes or even death [1].
Contaminants, commonly known also as risk factors, may have different characteristics depending on their origin. Physical contamination is caused by ubiquitous ionizing and nonionizing radiation. Micro-organisms and their metabolites or pollens can be considered as risk factors of biological origin. Chemical contaminants include endocrine disruptors or toxic metals [2].
Pollutants tend to accumulate in different organs and harm their functions. Poisoning or contaminant-derived diseases can be acute (episodic) or can develop over time (chronic intoxication). They are often accompanied by skin problems, breathing complications, convulsions, digestive disorders, or serious failures of the central nervous system and endocrine activity. The most terrifying effects, affecting even the progeny, are mutagenicity and carcinogenicity [3,4,5,6,7,8].
A good example of the consequence of high environmental pollution is the year to year decrease in the infertility of wild animals, domestic animals, or even humans. A negative effect of toxicants (decrease in concentration, motility, or longevity of spermatozoa) is often monitored on the individual or the group of individuals, however, the mechanism of action of toxicants on the cellular level is not studied enough. If so, most of the time only one compound is studied at a time and studies do not take into consideration the possible effect of synergism or antagonism of xenobiotics [9,10,11,12].
Previous studies imply that the exogenic effect of toxicants is strongly related to the enhanced production of reactive oxygen species (ROS) and reactive nitrogen species (RNS), resulting in the degradation of biomolecules or even apoptosis [13]. On the other hand, it is important to mention that ROS are necessary for the physiological processes of spermatozoa such as capacitation or acrosome reaction. Therefore, spermatozoa may be affected by several exogenic and endogenic factors where the determining variables are the imbalance between antioxidants and free radicals and appropriate proportion between individual components of seminal plasma [14].
The present article describes exogenous agents in general and summarizes the current knowledge about their effects on male reproductive system and their modes of action.

2. Environmental Pollution

The pollution of the environment has a serious consequence in the endangerment of human and animal health. It is caused primarily by growing industrial production, transportation, chemical substances used in agriculture [15,16], and pharmaceutical remedies [17]. Soil contamination and thus the pollution of foods of plant origin is one of the most pressing issues in discussion about food safety on the European [18] or even global [19] level.
Gonads and gametes serve as a very sensible and reliable barometer of the incidence of risk elements in the environment. They are affected via the degeneration of seminiferous epithelium, abortion of connection with the basal membrane, defects in spermatozoa development, and generation of ROS thereby reducing male fertility [20,21,22,23]. Donkin and Barres [24] report that environmental factors along with diet and lifestyle are reflected in spermatozoa epigenetics. More important, these genetic changes may be passed on to the next generations via epigenetic inheritance. We recognize three types of contaminants that can eventually cause environmental pollution and we divide them based on their character and appearance on physical biological and chemical contaminants [2].

2.1. Physical Contamination

The Glossary of Environment Statistics issued by the United Nations Department for Economic and Social Information and Policy Analysis defines physical pollution as pollution caused by color, suspended solids, foaming, thermal conditions, or radioactivity [25]. This definition was adopted by the Organization for Economic Cooperation and Development (OECD) and is still used today [26]. Color pollution is the result of color contamination by an inappropriate arrangement of colors that induces a disorder in the perception of the visual field within the natural or urban environment [27]. Suspended solids are contaminants of the water environment in the form of microplastics. Microplastics are serious polluting agents themselves, moreover, they may have a role as pathogen carriers. Their presence in a marine environment is a threat not only to aquatic flora and fauna but also to human food safety in the form of seafood and salt [28,29].
Temperature changes in the aquatic system may also cause thermal pollution which is reflected in degraded water quality. The source of thermal pollution is frequently found in the activity of power plants. The negative effect is then shown on soil erosion or on fish that exhibit thermal shock, metabolism alterations, and reproductive dysfunction [30,31]. Another water-related contaminant causing physical pollution is foaming. Due to the appearance of the foam on the surface of the freshwater, contamination can be easily visually recognizable. Foam pollution may find a cause in the natural processes of aquaculture or anthropogenic activity. Man-made pollution is often caused unintentionally by of oil, detergent, or lignosulfonate leaks. Foam lines are formed from the surfactants which reduce the tension of the water surface and enable the foam bubbles occurrence [32].
Radiation is an extensively occurring contaminant of the environment. Radiation can be divided based on the amount of emitted energy into ionizing and non-ionizing, which determinates the power and further features of the radiation. Non-ionizing radiation causes electron excitation which can induce heat generation. Ionizing radiation possesses enough energy to induce the emission of electrons from atoms and electrons being a threat to all living organisms [33,34]. Radioactive compounds are usually the waste of nuclear power generation, production of nuclear fuels, weapons development, biomedical interests, and industrial activities. However, radioactive contaminants can also originate in nature [35]. Radiation is the only exogenous agent of the group of physical contaminants that have a direct effect on male reproduction. As the ubiquitous aspect of the modern age, radiation may be considered a serious threat based on its emitted energy, frequency, and dose of exposure (Table 1).

2.2. Biological Contamination

The term biological contaminant covers all cases of contaminations induced by the biological activity of organisms in the environment. This includes all invasive plant and animal species, pollen, but concerning reproduction, the most frequent biological pollutants are microorganisms. Either microbes themselves or their metabolites cause air, water, soil, or food pollution [54,55,56,57]. The food chain contains numerous entries for contamination. The contamination of groceries is often associated with improper storage conditions while fresh products are considered safe and healthy. This bias is frequently promoted along with a healthy lifestyle. However, microbiological threats are present in every step of the farm-to-fork chain, including the soil, water sources, cultivation, harvesting, and processing [58]. In respect to one of the highest sources of contamination, water, the US Environmental Protection Agency identifies over 500 waterborne pathogens, including viruses, fungi, bacteria, protozoa [59]. Epidemiologists also warn against the HVAC (heating, ventilation, and air conditioning) technology and hand dryers in public restrooms when they are not regularly maintained, inspected for microbial pollution, and disinfected [60].
Male reproductive organs are prone to microbial infection and subsequential inflammations. The male urogenital tract is occupied by numerous bacteria including Escherichia coli, Proteus spp., Enterococcus spp., and other Gram-positive and Gram-negative bacteria. The presence of bacteria in the semen is called bacteriospermia and does not inevitably mean the pathological sign. On the contrary, the presence of Mycoplasma spp., Chlamydia spp. or other pathogenic bacteria are not appreciated. Sequela such as orchitis, epididymitis may be caused by Brucella spp., Mycobacterium leproe, Mycobacterium leproe, or uropathogenic Escherichia coli. In addition to epididymis and testis, Chlamydia trachomotis targets and causes inflammation of the urethra, prostate, and seminal vesicles. In certain cases, when the concentration of pathogenic bacteria is too excessive, the body responds with leukocytospermia—abnormally high concentration of white blood cells in ejaculate. The physiological regulation of this phenomenon is not sufficiently explained yet [60,61,62,63]. Some authors even did not find any or just weak associations between bacteriospermia and leukocytospermia [64,65].
Semen may be considered the vector of viral infection; however, the male reproductive system may also suffer from viral contamination. It has been documented that semen may be a host to approximately 27 viruses. This includes Adenoviruses, Ebola virus, Hepatitis virus (HPV) B and C, Zika virus, Epstein Barr virus, Human immunodeficiency virus (HIV), Mumps virus, several herpes viruses, Human T-cell lymphoma virus, SARS-CoV-2 virus, etc. [61,66,67]. Evidence on the direct effect of viruses on fertility has been reported by several studies. Some viruses affect only the spermatozoa by alteration of their motility and viability (Hepatitis B and C, SARS-CoV-2, HPV) [67,68,69]. On the other hand, the CoxsacKie virus, Mumps virus, HIV, Zika virus, HPV, Influenza virus target male reproductive organs—testis and epididymis [68,69,70,71,72]. In some cases of HPV infection, the targeted site might be just Sertoli cells. This phenomenon is called the “Sertoli cell-only” syndrome [71].

2.3. Chemical Contamination

Chemical contaminants turn into pollutants when accumulations are sufficient to undesirably affect the natural environment or to present a risk to living organisms. There are thousands of industrial chemicals identified as a hazard to humans, animals, and the environment. Therefore, governmental agencies regulate their production, storage, transportation, and disposal. Sources of chemical contamination contain agricultural activities, industrial and manufacturing activities, municipal waste, service-related activities, and resource extraction [73].

2.3.1. Heavy Metals

The term “heavy metals” defines a wide group of contaminating elements that are distinctive of their miscellaneous features, associated effects, and origin. Heavy metals of-ten appear as positively charged molecules that bind to negatively charged molecules of other elements to become a part of a compound. Ecotoxicological studies include the group of heavy metal elements like Cu, Zn, Cd, Hg, Pb, Cr, Ni, Mn, Fe, and semimetals As and Se. These metals are sometimes incorrectly indexed as toxic metals which is inaccurate since many metals are essential nutrients and at certain levels are not toxic at all [74,75]. Heavy metals fall into a group of trace elements. Their impact on the body may be diverse—metabolic, carcinogenic, or even mutagenic. The mode of action depends on several factors: the features of the element, a form of contact with the organism, the dose of the element, exposure time, type of absorption of the element, or bioaccumulation. The current research is aimed mainly at heavy metals present in industrial or former mining areas [76]. According to Arvay et al. [77], toxicity varies in dependence on mobility, solubility, pH, etc. Numerous studies proved that heavy metals accumulate in adipose tissues and consequently disrupt the functioning of internal organs and impair the nervous or endocrine system [78,79,80]. In general, compounds containing heavy metals are toxic, mutagenic, teratogenic, and carcinogenic for animals [81]. There are several ways of the entrance to the animal organism (e.g., consumption, inhalation, through the skin) that can cause severe intoxications [82]. Therefore, thorough, and periodic monitoring of health conditions is required in polluted areas [9,16,83]. The detrimental effects of heavy metals have been reported by numerous studies. Table 2 displays the most serious heavy metals-induced deteriorations reported in association with the male reproductive system.

2.3.2. Endocrine Disruptors (EDs)

Endocrine disruptors represent a large group of environmental xenobiotic com-pounds that can interfere with the biosynthesis, secretion, action, or metabolism of endogenous hormones, which ultimately leads to changes in the efficacy of these hormones [120,121]. EDs can be of natural origin (phytoestrogens, hormones, etc.) or are the result of anthropogenic activities (pharmaceuticals, dioxins, pesticides, etc.) [35]. Because most of them can interact with cell surfaces or nuclear receptors, they can cause alterations in cellular homeostasis even at extremely low concentrations, which places them in a special category of toxic substances in terms of health risks [122]. These substances are characterized by persistence and bioaccumulation properties, which are associated with the inhibition and disruption of physiological processes at the level of cells and molecular signaling pathways. The results are irreversible changes in the endocrine, cardiovascular, nervous, reproductive, and immune systems [123]. Due to their ability to interfere with estrogen, progesterone, and androgen receptors, endocrine disruptors pose extremely serious health risks in association with impairment of male reproductive functions [124]; at the forefront of discussions is infertility due to reduced sperm count, reduced sperm quality, and inhibition of steroidogenesis [7,125,126]. Many xenobiotics have endocrine disrupting properties, including industrial chemicals, solvents, polycyclic aromatic hydrocarbons, plasticizers, and compounds found in detergents, cosmetics, agricultural chemicals, and pesticides, as well as natural and synthetic hormones and drugs. These chemicals are widely distributed in the environment, especially through the trophic chain and wastewater [127,128]. At present, the attention of science in the field of EDs is focused mainly on synthetic industrial chemicals because of the absence of evolutionary adaptation to these xenobiotics [129]. These are plasticizers and other chemicals present in plastic as well as paper food packaging, which expose the human population to endocrine disruptors through food practically continuously [130]. This phenomenon has been confirmed by numerous studies, the results of which indicate increased concentrations of bisphenols, alkylphenols, phthalates, and perfluoroalkyl compounds in the saliva, urine, and milk of exposed individuals, but also in the food of daily consumption [131]. EDs also include many agrochemicals and pesticides, which have been shown endocrine disruptive activities in the living organism [132]. In particular, first-generation pesticides are a dangerous heritage for today’s population because they persist in soils, aquatic sediments, bioaccumulate in invertebrate and vertebrate tissues, and move up in trophic chains [133,134]. Numerous studies confirm that the increasing number of compounds released uncontrollably into the environment every year, which we classify as endocrine disruptors, harm animal and human health, and it is necessary to monitor their effects and consequences in organisms [7,135,136,137].

3. Mode of Action (MoA)

As listed earlier, there are three types of contaminants (physical, biological, and chemical) based on their characteristics, origin, and MoA. This implies their various effects on the functionality of organs and gametes. The biological system has its own mechanisms to prevent the toxicity of the reproductive system. The hematotesticular barrier (HTB) regulates the migration of some toxicants from blood to the testis, mature sperm chromatin is inactive and firmly coiled, defective spermatocytes are degraded and replaced. The imperfection of the HTB consists in the influx of lipophilic compounds allowing the exposure of vulnerable spermatogonia to toxicants and compromises male fertility [74]. HTB is one of the tightest barriers between blood and tissue, dividing seminiferous epithelium into the basal and apical parts. Also known as the blood–testis barrier, HTB differs from other tissue barriers by its structure, composed of tight junctions, ectoplasmic specializations, desmosomes, and gap junctions. This highly specific and unique structure provides a favorable microenvironment for meiosis and following the development of spermatids into spermatozoa [138]. Spermatogonia are localized in the basal compartment while primary and secondary spermatocytes along with round and elongating and already elongated spermatids are situated in the apical compartment [139].

3.1. Physical Pollutants

The MoA of radiation on male reproductive physiology is not clearly stated across the scientific literature. While ionizing radiation is considered dangerous due to the ability of electron liberation, non-ionizing radiation is supposedly safe as it lacks photon energy. However, non-ionizing radiation excites electrons which generates heat. It is assumed that heat generation stimulates OS production [33,44,140]. The spermatozoa of radiated individuals may contain microtubules with the modified arrangement, furthermore, disrupted mitochondria with up-regulated ROS generation may appear in radiation-exposed spermatozoa [141]. Excessive OS initiates adverse actions towards testicular tissue, mainly Sertoli cells, Leydig cells, and germ cells. The modulated integrity of testis indicates impaired spermatogenesis, apoptosis, and production of spermatozoa with functional and morphological damage. Moreover, male gametes may possess defected DNA [36,37,48,52]. A decreased number of viable Leydig cells causes alteration of testosterone production. This variation in androgen production impairs the whole hypothalamic-pituitary-adrenal axis [142]. The significant limitation of the topic of radiation and male reproduction arises in the scientific community. Biologists evaluate the risk of radiation based solely on the biological data (mainly OS production) while physicists look at the same problematics on the level of electrons with no biological relevance.

3.2. Biological Pollutants

Biological pollutants affect reproduction primarily from the microbial perspective. Bacterial contamination of the urogenital tract is associated with an enhanced level of leukocytes in the semen. Leukocytes generate ROS in their combat with an infection which may cause deleterious changes of spermatozoa and the integrity of their DNA [64]. The effect of mycotoxins on male reproduction needs to be remembered as well. As shown by Zheng et al. [143], zearalenone impairs reproductive functions. The results of in vitro administration of zearalenone were demonstrated on the Sertoli cells. Irreversible damage was detected damage to the cytoskeletal structure, namely the absence of both mitochondria and Golgi apparatus, and relocalization of vacuoles into the cytoplasm. Moreover, mycotoxins can interfere with the secretory functions of Sertoli cells. Most viruses affect only spermatozoa if at all. However, few other types target testicular and epididymal tis-sue and induce severe inflammation [68,69]. This process includes HTB, which forms an interface between the immune system and germ cells. Strong inflammation in combination with responding cytokines modulates the functionality of HTB. Comprised barrier enables the entrance of inflammation and may result in the formation of granulomas as a response to chronic inflammation. Moreover, inflammation induces excessive ROS pro-duction causing even superior damage to the testis, germ cells, and developing spermatozoa [144].

3.3. Chemical Pollutants

Chemical pollutants are probably the most recognized of all pollutants. Toxic heavy metals, due to their capability to accumulate in tissues, represent a threat as chronic toxicants. The toxic mechanisms of heavy metals are defined as ion imitation, interruption of cell signaling pathways, oxidative stress, altered gene expression, apoptosis, disruption of the testis–blood barrier, and inflammation. It has been previously revealed that toxic heavy metals alter Leydig cell development and induce Leydig cell tumors. Even low doses of these toxic agents alter the walls of seminiferous tubules, thinness the germinal epithelium, thus impairing the process of spermatogenesis. Heavy metal exposure also results in the altered weight of testes, cellular degeneration, interfered androgen hormones pro-duction, dilatated and congested blood vessels, and necrosis [9,89,101,145]. Elevated environmental concentrations of heavy metals are markedly displayed in the enhanced level of OS in seminal plasma [146].
Endocrine disruptors are associated mainly with imperceptible regulation of endocrine systems. The chemical structure of these pollutants mimics the natural hormones or interfere with the synthesis and secretion of the natural hormones. These agents are responsible not only for the improper development of sexual organs of the affected individual, but their effect may be also displayed on the health and sexual status of its progeny [7,137,147]. In addition to chemicals as polychlorinated bisphenols, organochlorine pesticides, and plasticizers and nonylphenols, it has been proposed, that heavy metals mercury, cadmium, and arsenic may also possess endocrine system modulating functions [148,149]. Several studies report the direct disrupting effect of EDs on the germ cells and Leydig cells via excessive generation of OS [150].

3.4. Oxidative Stress—A Common Feature

Oxygen is a biogenic element for all aerobic cells. It is necessary for the maintenance of normal cell functions, however, reactive oxygen species (ROS) which are formed as a by-product of the natural metabolism of oxygen may be harmful to the cell. The deciding factor is whether there is a balance between ROS generation and antioxidants which can scavenge free radicals [151]. Free radicals may be defined as an independently existing atom or molecule with an unpaired electron. By accepting or donating the electron molecule becomes a free radical. Reactive oxygen species and reactive nitrogen species (RNS) belong among the best known and most frequent free radicals [152]. ROS represent a wide category of molecules including radicals and non-radicals. Oxygen-derived radicals comprise hydroxyl ion (•OH), superoxide (O2•−), peroxyl (LOO•), hypochlorous acid (HOCl), etc. Non-radicals include ozone (O3), singlet oxygen (1O2), peroxide substances (H2O2), and others [152,153]. Nitrogen-derived radicals are nitric oxide (•NO), nitrous oxide (N2O), peroxynitrite (ONOO-), nitroxyl anion (NO−), and peroxynitrous acid (ONOOH).
Metabolism and the utilization of oxygen is an essential requirement of male gametes. Free radicals play an important role in several physiological processes of the reproductive tract [154]. Spermatozoa themselves generate ROS which is necessary for capacitation, hyperactivation, acrosome reaction, and sperm-oocyte fusion [14]. Each ejaculate contains potential sources of ROS. Often, these sources are leukocytes and neutrophils, which apply their cytotoxic mechanism against cells and pathogens and produce high levels of ROS [155].
The endogenous production of O2●− is caused by cell respiration. This radical is by itself relatively non-reactive, but the presence of H+ leads to the formation of H2O2, which is largely involved in the lipid peroxidation of the plasma membrane [156,157] abundant in PUFA [158,159]. Gosalvez et al. [14] report that by the action of enzymatic antioxidants H2O2 is catalyzed to water and oxygen. The external sources of ROS are associated with an individual’s diet and the environment in which the individual lives. Indirect and direct effects on male infertility are induced by industrial intermediate products and wastes [160], smoking and alcohol consumption [161,162,163], obesity [164], diabetes [165], physical exercise [166], psychological stress [167], aging [168], or the presence of increased levels of toxic heavy metals in the environment [169,170].
NO, the major RNS, is formed of L-arginine by redox-reaction via nitric oxide synthase (NOS). This reaction necessitates oxygen and several cofactors. RNS are invaluable for numerous physiological processes in male reproduction, demonstrating their importance in intracellular signaling pathways [142]. Moreover, NO regulates the timing of the opening and closing of tight junctions of HTB thus prevents xenobiotics from entering the seminiferous tubules. Further, RNS are similarly as ROS involved in capacitation, acrosome reaction, hyperactivation, and oocyte-spermatozoa fusion. An excessive amount of RNS results in stimulation of apoptosis, inhibition of Leydig cell steroidogenesis. Clinically, RNS is often associated with leukocytospermia, varicocele, and erectile dysfunction [171].
The exposure to oxidative stress may result in adaptation (increased activity of defense mechanisms), damage to macromolecules (DNA fragmentation, protein modifications, lipid peroxidation) [172,173], or cell death (apoptosis, or even necrosis with a wider impact on surrounding cells and tissue) [174]. The effect of OS may be also mitigated by antioxidants by oral administration [175,176,177,178] or direct supplementation of reproduction-associated cells [179,180,181,182,183].

4. Conclusions

Environmental pollutants have been determined as a risk factor to the overall health status of both humans and animals. The synergism of several contaminants and their bioaccumulation may lead to the induction of oxidative stress, resulting in cellular disruption, histological damage, endocrine disruption, and possible transgenerational effects. It is necessary to also consider antagonistic effects. The reproductive system, due to its high sensitivity, is considered the plausible marker of environmental quality that is applicable for humans as well as for various domestic and wild animals. Plenty of xenobiotics target the testis and impair their function. The male reproductive system possesses molecular repairing mechanisms that enable the limited but continuous production of viable gametes. Nevertheless, it is important to monitor and protect the environment by all means in order to maintain the fertility of humans and animals.

Author Contributions

Conceptualization, F.T., H.G., N.L., R.S., and P.M.; methodology, F.T., and P.M.; writing—original draft preparation, F.T., H.G., N.L., R.S., and P.M.; writing—review and editing, N.L., R.S., and P.M.; supervision, N.L., R.S., and P.M. All authors have read and agreed to the published version of the manuscript.

Funding

This publication was supported by the Operational program Integrated Infrastructure within the project: Creation of nuclear herds of dairy cattle with a requirement for high health status through the use of genomic selection, innovative biotechnological methods, and optimal management of breeding, NUKLEUS 313011V387, co-financed by the European Regional Development Fund. This work was supported also by projects of the Scientific Grant Agency of the Ministry of Education, Science, Research and Sport of the Slovak Republic (projects VEGA 1/0539/18 and VEGA 1/0038/19); The Slovak Research and Development Agency (projects APVV-16-0289) and Cultural and Educational Agency of the Ministry of Education, Science, Research and Sport of the Slovak Republic (projects KEGA 010/SPU-4/2018 and KEGA 034SPU-4/2019).

Institutional Review Board Statement

Not applicable.

Informed Consent Statement

Not applicable.

Data Availability Statement

Not applicable.

Conflicts of Interest

The authors declare no conflict of interest.

References

  1. Liang, W.; Yang, M. Urbanization, Economic Growth and Environmental Pollution: Evidence from China. Sustain. Comput. Inf. Syst. 2019, 21, 1–9. [Google Scholar] [CrossRef]
  2. Saleh, H.E.-D.M.; Aglan, R. Heavy Metals; BoD–Books on Demand: Norderstedt, Germany, 2018. [Google Scholar]
  3. Roychoudhury, S.; Nath, S.; Massanyi, P.; Stawarz, R.; Kacaniova, M.; Kolesarova, A. Copper-Induced Changes in Reproductive Functions: In Vivo and In Vitro Effects. Physiol. Res. 2016, 65, 11–22. [Google Scholar] [CrossRef]
  4. Forgacs, Z.; Massányi, P.; Lukac, N.; Somosy, Z. Reproductive Toxicology of Nickel–Review. J. Environ. Sci. Health Part A 2012, 47, 1249–1260. [Google Scholar] [CrossRef]
  5. Jambor, T.; Kovacikova, E.; Greifova, H.; Kovacik, A.; Libova, L.; Lukac, N. Assessment of the Effective Impact of Bisphenols on Mitochondrial Activity and Steroidogenesis in a Dose-Dependency in Mice TM3 Leydig Cells. Physiol. Res. 2019, 68, 689–693. [Google Scholar] [CrossRef]
  6. Jambor, T.; Kovacikova, E. The Evaluation of Evidence Bisphenol A Exposure and Human Reproductive Health: A Review. Arch. Ecotoxicol. 2019, 1, 11–17. [Google Scholar] [CrossRef]
  7. Jambor, T.; Greifova, H.; Kovacik, A.; Kovacikova, E.; Massanyi, P.; Forgacs, Z.; Lukac, N. Identification of in Vitro Effect of 4-Octylphenol on the Basal and Human Chorionic Gonadotropin (HCG) Stimulated Secretion of Androgens and Superoxide Radicals in Mouse Leydig Cells. J. Environ. Sci. Health Part A 2019, 54, 759–767. [Google Scholar] [CrossRef]
  8. Alimba, C.G.; Faggio, C. Microplastics in the Marine Environment: Current Trends in Environmental Pollution and Mechanisms of Toxicological Profile. In Environmental Toxicology and Pharmacology; Elsevier B.V.: Amsterdam, The Netherlands, 2019; pp. 61–74. [Google Scholar]
  9. Massányi, P.; Massányi, M.; Madeddu, R.; Stawarz, R.; Lukáč, N. Effects of Cadmium, Lead, and Mercury on the Structure and Function of Reproductive Organs. Toxics 2020, 8, 94. [Google Scholar] [CrossRef] [PubMed]
  10. Kovacik, A.; Tirpak, F.; Tomka, M.; Miskeje, M.; Tvrda, E.; Arvay, J.; Andreji, J.; Slanina, T.; Gabor, M.; Hleba, L. Trace Elements Content in Semen and Their Interactions with Sperm Quality and RedOx Status in Freshwater Fish Cyprinus Carpio: A Correlation Study. J. Trace Elem. Med. Biol. 2018, 50, 399–407. [Google Scholar] [CrossRef]
  11. Kim, H.; Yim, B.; Bae, C.; Lee, Y.M. Acute Toxicity and Antioxidant Responses in the Water Flea Daphnia Magna to Xenobiotics (Cadmium, Lead, Mercury, Bisphenol A, and 4-Nonylphenol). Toxicol. Environ. Health Sci. 2017, 9, 41–49. [Google Scholar] [CrossRef]
  12. Naderi, M.; Wong, M.Y.L.; Gholami, F. Developmental Exposure of Zebrafish (Danio Rerio) to Bisphenol-S Impairs Subsequent Reproduction Potential and Hormonal Balance in Adults. Aquat. Toxicol. 2014, 148, 195–203. [Google Scholar] [CrossRef] [PubMed]
  13. El-Demerdash, F.M.; Tousson, E.M.; Kurzepa, J.; Habib, S.L. Xenobiotics, Oxidative Stress, and Antioxidants. Oxid. Med. Cell. Longev. 2018, 2018, 1–2. [Google Scholar] [CrossRef] [Green Version]
  14. Gosalvez, J.; Tvrda, E.; Agarwal, A. Free Radical and Superoxide Reactivity Detection in Semen Quality Assessment: Past, Present, and Future. J. Assist. Reprod. Genet. 2017, 34, 697–707. [Google Scholar] [CrossRef]
  15. Maia, R.S.; Babinski, M.A.; Figueiredo, M.A.; Chagas, M.A.; Costa, W.S.; Sampaio, F.J. Concentration of Elastic System Fibers in the Corpus Cavernosum, Corpus Spongiosum, and Tunica Albuginea in the Rabbit Penis. Int. J. Impot. Res. 2006, 18, 121–125. [Google Scholar] [CrossRef] [Green Version]
  16. Kovacik, A.; Arvay, J.; Tusimova, E.; Harangozo, L.; Tvrda, E.; Zbynovska, K.; Cupka, P.; Andrascikova, S.; Tomas, J.; Massanyi, P. Seasonal Variations in the Blood Concentration of Selected Heavy Metals in Sheep and Their Effects on the Biochemical and Hematological Parameters. Chemosphere 2017, 168, 365–371. [Google Scholar] [CrossRef]
  17. Yadav, A.; Rene, E.R.; Mandal, M.K.; Dubey, K.K. Threat and Sustainable Technological Solution for Antineoplastic Drugs Pollution: Review on a Persisting Global Issue. Chemosphere 2021, 263, 128285. [Google Scholar] [CrossRef]
  18. Wall, D.H.; Bardgett, R.D.; Behan-Pelletier, V.; Ritz, K.; Herrick, J.E.; Jones, T.H.; Six, J.; Strong, D.R.; van der Putten, W.H. Soil Ecology and Ecosystem Services; OUP Oxford: Oxford, UK, 2012. [Google Scholar]
  19. Kong, X. China Must Protect High-Quality Arable Land. Nature 2014, 506, 7. [Google Scholar] [CrossRef]
  20. Tung, C.; Lin, C.; Harvey, B.; Fiore, A.G.; Ardon, F.; Wu, M.; Suarez, S.S. Fluid Viscoelasticity Promotes Collective Swimming of Sperm. Sci. Rep. 2017, 7, 1–9. [Google Scholar] [CrossRef] [PubMed]
  21. Atig, F.; Raffa, M.; Ali, H.B.; Abdelhamid, K.; Saad, A.; Ajina, M. Altered Antioxidant Status and Increased Lipid Per-Oxidation in Seminal Plasma of Tunisian Infertile Men. Int. J. Biol. Sci. 2012, 8, 139. [Google Scholar] [CrossRef] [PubMed] [Green Version]
  22. Juyena, N.S.; Stelletta, C. Seminal Plasma: An Essential Attribute to Spermatozoa. J. Androl. 2012, 33, 536–551. [Google Scholar] [CrossRef] [PubMed] [Green Version]
  23. Halo, M., Jr.; Tirpak, F.; Tvrda, E.; Błaszczyk, M.; Lipova, P.; Binkowski, Ł.; Massanyi, P. Microelements and macroelements in seminal plasma affect oxidative balance of stallion semen. In Proceedings of the MendelNet 2017—International PhD Students Conference, Brno, Czech Republic, 8–9 November 2017; Mendel University in Brno: Brno, Czech Republic, 2017; pp. 685–690. [Google Scholar]
  24. Donkin, I.; Barrès, R. Sperm Epigenetics and Influence of Environmental Factors. In Molecular Metabolism; Elsevier GmbH: Munich, Germany, 2018; pp. 1–11. [Google Scholar]
  25. United Nations Statistics Division—Glossary of Environment Statistics. Available online: https://unstats.un.org/unsd/environmentgl/gesform.asp?getitem=892 (accessed on 28 January 2021).
  26. OECD—Glossary of Statistical Terms. Available online: https://stats.oecd.org/glossary/detail.asp?ID=1336 (accessed on 28 January 2021).
  27. Arrarte-Grau, M. Color Pollution. In Encyclopedia of Color Science and Technology, 1st ed.; Luo, M.R., Ed.; Springer: New York, NY, USA, 2016; pp. 351–352. [Google Scholar]
  28. Peixoto, D.; Pinheiro, C.; Amorim, J.; Oliva-Teles, L.; Guilhermino, L.; Vieira, M.N. Microplastic Pollution in Commercial Salt for Human Consumption: A Review. In Estuarine, Coastal and Shelf Science; Academic Press: Cambridge, MA, USA, 2019; pp. 161–168. [Google Scholar]
  29. Andrady, A.L. The Plastic in Microplastics: A Review. In Marine Pollution Bulletin; Elsevier Ltd.: Amsterdam, The Netherlands, 2017; pp. 12–22. [Google Scholar]
  30. Bobat, A. Thermal Pollution Caused by Hydropower Plants BT—Energy Systems and Management; Bilge, A.N., Toy, A.Ö., Günay, M.E., Eds.; Springer International Publishing: Cham, Switzerland, 2015; pp. 19–32. [Google Scholar]
  31. Verones, F.; Hanafiah, M.M.; Pfister, S.; Huijbregts, M.A.J.; Pelletier, G.J.; Koehler, A. Characterization Factors for Thermal Pollution in Freshwater Aquatic Environments. Environ. Sci. Technol. 2010, 44, 9364–9369. [Google Scholar] [CrossRef] [PubMed]
  32. Schilling, K.; Zessner, M. Foam in the Aquatic Environment. In Water Research; Elsevier Ltd.: Amsterdam, The Netherlands, 2011; pp. 4355–4366. [Google Scholar]
  33. Tirpak, F.; Slanina, T.; Tomka, M.; Zidek, R.; Halo, M.; Ivanic, P.; Gren, A.; Formicki, G.; Stachanczyk, K.; Lukac, N.; et al. Exposure to Non-Ionizing Electromagnetic Radiation of Public Risk Prevention Instruments Threatens the Quality of Spermatozoids. Reprod. Domest. Anim. 2019, 54, 150–159. [Google Scholar] [CrossRef]
  34. Havas, M. When Theory and Observation Collide: Can Non-Ionizing Radiation Cause Cancer? In Environmental Pollution; Elsevier Ltd.: Amsterdam, The Netherlands, 2017; pp. 501–505. [Google Scholar]
  35. Monneret, C. What Is an Endocrine Disruptor? C. R. Biol. 2017, 340, 403–405. [Google Scholar] [CrossRef]
  36. Almášiová, V.; Holovská, K.; Šimaiová, V.; Beňová, K.; Raček, A.; Račeková, E.; Martončíková, M.; Mihálik, J.; Horváthová, F.; Tarabová, L. The Thermal Effect of 2.45 GHz Microwave Radiation on Rat Testes. Acta Vet. Brno 2018, 86, 413–419. [Google Scholar] [CrossRef] [Green Version]
  37. Pandey, N.; Giri, S. Melatonin Attenuates Radiofrequency Radiation (900 MHz)-Induced Oxidative Stress, DNA Damage and Cell Cycle Arrest in Germ Cells of Male Swiss Albino Mice. Toxicol. Ind. Health 2018, 34, 315–327. [Google Scholar] [CrossRef]
  38. Wu, H.; Wang, D.; Shu, Z.; Zhou, H.; Zuo, H.; Wang, S.; Li, Y.; Xu, X.; Li, N.; Peng, R. Cytokines Produced by Microwave-radiated Sertoli Cells Interfere with Spermatogenesis in Rat Testis. Andrologia 2012, 44, 590–599. [Google Scholar] [CrossRef]
  39. Dasdag, S.; Taş, M.; Akdag, M.Z.; Yegin, K. Effect of Long-Term Exposure of 2.4 GHz Radiofrequency Radiation Emitted from Wi-Fi Equipment on Testes Functions. Electromagn. Biol. Med. 2015, 34, 37–42. [Google Scholar] [CrossRef]
  40. Singh, Y.; Behari, J. The Effect of Whole Body Exposure of 50 GHz Microwave Radiation on Sperm Counts in Rats; School of Environmental Sciences, Jawaharlal Nehru University: New Delhi, India, 2005. [Google Scholar]
  41. Tas, M.; Dasdag, S.; Akdag, M.Z.; Cirit, U.; Yegin, K.; Seker, U.; Ozmen, M.F.; Eren, L.B. Long-Term Effects of 900 MHz Radiofrequency Radiation Emitted from Mobile Phone on Testicular Tissue and Epididymal Semen Quality. Electromagn. Biol. Med. 2014, 33, 216–222. [Google Scholar] [CrossRef]
  42. Mailankot, M.; Kunnath, A.P.; Jayalekshmi, H.; Koduru, B.; Valsalan, R. Radio Frequency Electromagnetic Radiation (RF-EMR) from GSM (0.9/1.8 GHz) Mobile Phones Induces Oxidative Stress and Reduces Sperm Motility in Rats. Clinics 2009, 64, 561–565. [Google Scholar] [CrossRef] [Green Version]
  43. Chauhan, P.; Verma, H.N.; Sisodia, R.; Kesari, K.K. Microwave Radiation (2.45 GHz)-Induced Oxidative Stress: Whole-Body Exposure Effect on Histopathology of Wistar Rats. Electromagn. Biol. Med. 2017, 36, 20–30. [Google Scholar] [CrossRef]
  44. Lukac, N.; Massanyi, P.; Roychoudhury, S.; Capcarova, M.; Tvrda, E.; Knazicka, Z.; Kolesarova, A.; Danko, J. In Vitro Effects of Radiofrequency Electromagnetic Waves on Bovine Spermatozoa Motility. J. Environ. Sci. Health Part A 2011, 46, 1417–1423. [Google Scholar] [CrossRef]
  45. Roychoudhury, S.; Jedlicka, J.; Parkanyi, V.; Rafay, J.; Ondruska, L.; Massanyi, P.; Bulla, J. Influence of a 50 Hz Extra Low Frequency Electromagnetic Field on Spermatozoa Motility and Fertilization Rates in Rabbits. J. Environ. Sci. Health Part A 2009, 44, 1041–1047. [Google Scholar] [CrossRef]
  46. Bernabò, N.; Tettamanti, E.; Pistilli, M.G.; Nardinocchi, D.; Berardinelli, P.; Mattioli, M.; Barboni, B. Effects of 50 Hz Extremely Low Frequency Magnetic Field on the Morphology and Function of Boar Spermatozoa Capacitated In Vitro. Theriogenology 2007, 67, 801–815. [Google Scholar] [CrossRef]
  47. Li, H.; He, Y.; Yan, J.; Zhao, Q.; Di, C.; Zhang, H. Comparative Proteomics Reveals the Underlying Toxicological Mechanism of Low Sperm Motility Induced by Iron Ion Radiation in Mice. Reprod. Toxicol. 2016, 65, 148–158. [Google Scholar] [CrossRef] [PubMed]
  48. Shaban, N.Z.; Ahmed Zahran, A.M.; El-Rashidy, F.H.; Abdo Kodous, A.S. Protective Role of Hesperidin against γ-Radiation-Induced Oxidative Stress and Apoptosis in Rat Testis. J. Biol. Res. 2017, 24, 5. [Google Scholar] [CrossRef] [Green Version]
  49. Naeimi, R.A.; Talebpour Amiri, F.; Khalatbary, A.R.; Ghasemi, A.; Zargari, M.; Ghesemi, M.; Hosseinimehr, S.J. Atorvastatin Mitigates Testicular Injuries Induced by Ionizing Radiation in Mice. Reprod. Toxicol. 2017, 72, 115–121. [Google Scholar] [CrossRef]
  50. Ding, J.; Wang, H.; Wu, Z.-B.; Zhao, J.; Zhang, S.; Li, W. Protection of Murine Spermatogenesis Against Ionizing Radiation-Induced Testicular Injury by a Green Tea Polyphenol. Biol. Reprod. 2015, 92, 1–13. [Google Scholar] [CrossRef]
  51. Li, H.Y.; Zhang, H. Proteome Analysis for Profiling Infertility Markers in Male Mouse Sperm after Carbon Ion Radiation. Toxicology 2013, 306, 85–92. [Google Scholar] [CrossRef]
  52. Ji, H.-J.; Wang, D.-M.; Wu, Y.-P.; Niu, Y.-Y.; Jia, L.-L.; Liu, B.-W.; Feng, Q.-J.; Feng, M.-L. Wuzi Yanzong Pill, a Chinese Polyherbal Formula, Alleviates Testicular Damage in Mice Induced by Ionizing Radiation. BMC Complement. Altern. Med. 2016, 16, 509. [Google Scholar] [CrossRef] [Green Version]
  53. Homma-Takeda, S.; Nishimura, Y.; Watanabe, Y.; Yukawa, M. Site-Specific Changes in Zinc Levels in the Epididymis of Rats Exposed to Ionizing Radiation. Nucl. Instrum. Methods Phys. Res. Sect. B Beam Interact. Mater. Atoms 2007, 260, 236–239. [Google Scholar] [CrossRef]
  54. Suzuki, Y.; Teranishi, K.; Matsuwaki, T.; Nukazawa, K.; Ogura, Y. Effects of Bacterial Pollution Caused by a Strong Typhoon Event and the Restoration of a Recreational Beach: Transitions of Fecal Bacterial Counts and Bacterial Flora in Beach Sand. Sci. Total Environ. 2018, 640–641, 52–61. [Google Scholar] [CrossRef]
  55. Nenna, R.; Evangelisti, M.; Frassanito, A.; Scagnolari, C.; Pierangeli, A.; Antonelli, G.; Nicolai, A.; Arima, S.; Moretti, C.; Papoff, P.; et al. Respiratory Syncytial Virus Bronchiolitis, Weather Conditions and Air Pollution in an Italian Urban Area: An Observational Study. Environ. Res. 2017, 158, 188–193. [Google Scholar] [CrossRef]
  56. Elliott, M. Biological Pollutants and Biological Pollution—An Increasing Cause for Concern. Mar. Pollut. Bull. 2003, 46, 275–280. [Google Scholar] [CrossRef]
  57. Spevakova, I.; Fernandez-Cruz, M.-L.; Tokarova, K.; Greifova, H.; Capcarova, M. The Protective Effect of Stilbenes Resveratrol and Pterostilbene Individually and Combined with Mycotoxin Citrinin in Human Adenocarcinoma HT-29 Cell Line In Vitro. J. Environ. Sci. Health Part A 2021, 56, 75–88. [Google Scholar] [CrossRef]
  58. Machado-Moreira, B.; Richards, K.; Brennan, F.; Abram, F.; Burgess, C.M. Microbial Contamination of Fresh Produce: What, Where, and How? Compr. Rev. Food Sci. Food Saf. 2019, 18, 1727–1750. [Google Scholar] [CrossRef] [PubMed] [Green Version]
  59. Ashbolt, N.J. Microbial Contamination of Drinking Water and Human Health from Community Water Systems. Curr. Environ. Health Rep. 2015, 2, 95–106. [Google Scholar] [CrossRef] [Green Version]
  60. Liu, Z.; Ma, S.; Cao, G.; Meng, C.; He, B.J. Distribution Characteristics, Growth, Reproduction and Transmission Modes and Control Strategies for Microbial Contamination in HVAC Systems: A Literature Review. In Energy and Buildings; Elsevier Ltd.: Amsterdam, The Netherlands, 2018; pp. 77–95. [Google Scholar]
  61. Peeling, R.; Embree, J. Screening for Sexually Transmitted Infection Pathogens in Semen Samples. Can. J. Infect. Dis. Med. Microbiol. 2005, 16, 73–76. [Google Scholar] [CrossRef] [PubMed]
  62. Rusz, A.; Pilatz, A.; Wagenlehner, F.; Linn, T.; Diemer, T.; Schuppe, H.C.; Lohmeyer, J.; Hossain, H.; Weidner, W. Influence of Urogenital Infections and Inflammation on Semen Quality and Male Fertility. World J. Urol. 2012, 30, 23–30. [Google Scholar] [CrossRef]
  63. Weidner, W.; Pilatz, A.; Diemer, T.; Schuppe, H.C.; Rusz, A.; Wagenlehner, F. Male Urogenital Infections: Impact of Infection and Inflammation on Ejaculate Parameters. World J. Urol. 2013, 31, 717–723. [Google Scholar] [CrossRef] [PubMed]
  64. Aitken, R.J.; Baker, M.A. Oxidative Stress, Spermatozoa and Leukocytic Infiltration: Relationships Forged by the Opposing Forces of Microbial Invasion and the Search for Perfection. J. Reprod. Immunol. 2013, 100, 11–19. [Google Scholar] [CrossRef]
  65. Domes, T.; Lo, K.C.; Grober, E.D.; Mullen, J.B.M.; Mazzulli, T.; Jarvi, K. The Incidence and Effect of Bacteriospermia and Elevated Seminal Leukocytes on Semen Parameters. Fertil. Steril. 2012, 97, 1050–1055. [Google Scholar] [CrossRef]
  66. Salam, A.P.; Horby, P.W. The Breadth of Viruses in Human Semen. Emerg. Infect. Dis. 2017, 23, 1922. [Google Scholar] [CrossRef]
  67. Gacci, M.; Coppi, M.; Baldi, E.; Sebastianelli, A.; Zaccaro, C.; Morselli, S.; Pecoraro, A.; Manera, A.; Nicoletti, R.; Liaci, A.; et al. Semen Impairment and Occurrence of SARS-CoV-2 Virus in Semen after Recovery from COVID-19. Hum. Reprod. 2021. [CrossRef]
  68. Liu, W.; Han, R.; Wu, H.; Han, D. Viral Threat to Male Fertility. Andrologia 2018, 50, e13140. [Google Scholar] [CrossRef] [Green Version]
  69. Dejucq, N.; Jégou, B. Viruses in the Mammalian Male Genital Tract and Their Effects on the Reproductive System. Microbiol. Mol. Biol. Rev. 2001, 65, 208–231. [Google Scholar] [CrossRef] [Green Version]
  70. Garolla, A.; Pizzol, D.; Bertoldo, A.; Menegazzo, M.; Barzon, L.; Foresta, C. Sperm Viral Infection and Male Infertility: Focus on HBV, HCV, HIV, HPV, HSV, HCMV, and AAV. J. Reprod. Immunol. 2013, 100, 20–29. [Google Scholar] [CrossRef]
  71. Martorell, M.; Gil-Salom, M.; Pérez-Vallés, A.; Garcia, J.A.; Rausell, N.; Senpere, A. Presence of Human Papillomavirus DNA in Testicular Biopsies from Nonobstructive Azoospermic Men. Arch. Pathol. Lab. Med. 2005, 129, 1132–1136. [Google Scholar] [CrossRef]
  72. Roychoudhury, S.; Das, A.; Jha, N.K.; Kesari, K.K.; Roychoudhury, S.; Jha, S.K.; Kosgi, R.; Choudhury, A.P.; Lukac, N.; Madhu, N.R. Viral Pathogenesis of SARS-CoV-2 Infection and Male Reproductive Health. Open Biol. 2021, 11, 200347. [Google Scholar] [CrossRef]
  73. Brusseau, M.L.; Artiola, J.F. Chemical Contaminants. In Environmental and Pollution Science, 3rd ed.; Brusseau, M.L., Pepper, I.L., Gerba, C.P., Eds.; Academic Press: Cambridge, MA, USA, 2019; pp. 175–190. [Google Scholar]
  74. Lejeune, T.; Delvaux, P. Human Spermatozoa: Maturation, Capacitation and Abnormalities; Human Reproductive System—Anatomy, Roles, and Disorders Series; Nova Biomedical Books: Hauppauge, NY, USA, 2010. [Google Scholar]
  75. Halo, M.; Tirpák, F.; Dano, A.; Zbynovská, K.; Kovácik, A.; Ondruška, L.; Gren, A.; Lukác, N.; Massányi, P. Zinc Affects Rabbit Spermatozoa in Vitro: Effects on Motility and Viability. J. Microbiol. Biotechnol. Food Sci. 2018, 8, 901–904. [Google Scholar]
  76. Árvay, J.; Demková, L.; Hauptvogl, M.; Michalko, M.; Bajčan, D.; Stanovič, R.; Tomáš, J.; Hrstková, M.; Trebichalský, P. Assessment of Environmental and Health Risks in Former Polymetallic Ore Mining and Smelting Area, Slovakia: Spatial Distribution and Accumulation of Mercury in Four Different Ecosystems. Ecotoxicol. Environ. Saf. 2017, 144, 236–244. [Google Scholar] [CrossRef]
  77. Árvay, J.; Tomáš, J.; Hauptvogl, M.; Massányi, P.; Harangozo, Ľ.; Tóth, T.; Stanovič, R.; Bryndzová, Š.; Bumbalová, M. Human Exposure to Heavy Metals and Possible Public Health Risks via Consumption of Wild Edible Mushrooms from Slovak Paradise National Park, Slovakia. J. Environ. Sci. Health Part B 2015, 50, 833–843. [Google Scholar] [CrossRef]
  78. Waisberg, M.; Joseph, P.; Hale, B.; Beyersmann, D. Molecular and Cellular Mechanisms of Cadmium Carcinogenesis. In Toxicology; Elsevier Ireland Ltd.: Shannon, Ireland, 2003; pp. 95–117. [Google Scholar]
  79. Bocca, B.; Alimonti, A.; Petrucci, F.; Violante, N.; Sancesario, G.; Forte, G.; Senofonte, O. Quantification of Trace Elements by Sector Field Inductively Coupled Plasma Mass Spectrometry in Urine, Serum, Blood and Cerebrospinal Fluid of Patients with Parkinson’s Disease. Spectrochim. Acta Part B At. Spectrosc. 2004, 59, 559–566. [Google Scholar] [CrossRef]
  80. Wang, W.-X. Dietary Toxicity of Metals in Aquatic Animals: Recent Studies and Perspectives. Chin. Sci. Bull. 2013, 58, 203–213. [Google Scholar] [CrossRef] [Green Version]
  81. Jomova, K.; Valko, M. Advances in Metal-Induced Oxidative Stress and Human Disease. In Toxicology; Elsevier: Amsterdam, The Netherlands, 2011; pp. 65–87. [Google Scholar]
  82. Alissa, E.M.; Ferns, G.A. Heavy Metal Poisoning and Cardiovascular Disease. J. Toxicol. 2011, 2011, 870125. [Google Scholar] [CrossRef] [PubMed]
  83. Massanyi, P.; Stawarz, R.; Halo, M.; Formicki, G.; Lukac, N.; Cupka, P.; Schwarcz, P.; Kovacik, A.; Tusimova, E.; Kovacik, J. Blood Concentration of Copper, Cadmium, Zinc and Lead in Horses and Its Relation to Hematological and Biochemical Parameters. J. Environ. Sci. Health Part A 2014, 49, 973–979. [Google Scholar] [CrossRef]
  84. Toman, R.; Massányi, P.; Uhrin, V. Changes in the Testis and Epididymis of Rabbits after an Intraperitoneal and Peroral Administration of Cadmium. Trace Elem. Electrol. 2002, 19, 114–117. [Google Scholar]
  85. Han, C.; Zhu, Y.; Yang, Z.; Fu, S.; Zhang, W.; Liu, C. Protective Effect of Polygonatum Sibiricum against Cadmium-Induced Testicular Injury in Mice through Inhibiting Oxidative Stress and Mitochondria-Mediated Apoptosis. J. Ethnopharmacol. 2020, 261, 113060. [Google Scholar] [CrossRef]
  86. Ren, Y.; Shao, W.; Zuo, L.; Zhao, W.; Qin, H.; Hua, Y.; Lu, D.; Mi, C.; Zeng, S.; Zu, L. Mechanism of Cadmium Poisoning on Testicular Injury in Mice. Oncol. Lett. 2019, 18, 1035–1042. [Google Scholar] [CrossRef] [Green Version]
  87. Abarikwu, S.O.; Oruitemeka, S.; Uwadileke, I.A.; Omeodu, S.I.; Okoye, N.F.; Mgbudom-Okah, C.J.; Ohanador, R. Oral Administration of Cadmium Depletes Intratesticular and Epididymal Iron Levels and Inhibits Lipid Peroxidation in the Testis and Epididymis of Adult Rats. J. Trace Elem. Med. Biol. 2018, 48, 213–223. [Google Scholar] [CrossRef]
  88. Zhang, Y.; Li, Y.; Zhang, J.; Qi, X.; Cui, Y.; Yin, K.; Lin, H. Cadmium Induced Inflammation and Apoptosis of Porcine Epididymis via Activating RAF1/MEK/ERK and NF-ΚB Pathways. Toxicol. Appl. Pharmacol. 2021, 415, 115449. [Google Scholar] [CrossRef]
  89. Adamkovicova, M.; Toman, R.; Cabaj, M.; Massanyi, P.; Martiniakova, M.; Omelka, R.; Krajcovicova, V.; Duranova, H. Effects of Subchronic Exposure to Cadmium and Diazinon on Testis and Epididymis in Rats. Sci. World J. 2014, 2014, 632581. [Google Scholar] [CrossRef] [Green Version]
  90. Nna, V.U.; Ujah, G.A.; Mohamed, M.; Etim, K.B.; Igba, B.O.; Augustine, E.R.; Osim, E.E. Cadmium Chloride–Induced Testicular Toxicity in Male Wistar Rats; Prophylactic Effect of Quercetin, and Assessment of Testicular Recovery Following Cadmium Chloride Withdrawal. Biomed. Pharmacother. 2017, 94, 109–123. [Google Scholar] [CrossRef]
  91. Tvrdá, E.; Kňažická, Z.; Lukáčová, J.; Schneidgenová, M.; Goc, Z.; Greń, A.; Szabó, C.; Massányi, P.; Lukáč, N. The Impact of Lead and Cadmium on Selected Motility, Prooxidant and Antioxidant Parameters of Bovine Seminal Plasma and Spermatozoa. J. Environ. Sci. Health Part A 2013, 48, 1292–1300. [Google Scholar] [CrossRef]
  92. Olaniyi, K.S.; Amusa, O.A.; Oniyide, A.A.; Ajadi, I.O.; Akinnagbe, N.T.; Babatunde, S.S. Protective Role of Glutamine against Cadmium-Induced Testicular Dysfunction in Wistar Rats: Involvement of G6PD Activity. Life Sci. 2020, 242, 117250. [Google Scholar] [CrossRef]
  93. Liu, D.; Wan, J.; Liu, Z.; Zhao, Z.; Zhang, G.; Leng, Y. Determination of Cadmium Induced Acute and Chronic Reproductive Toxicity with Raman Spectroscopy. Lasers Med. Sci. 2020, 35, 1919–1926. [Google Scholar] [CrossRef]
  94. Roychoudhury, S.; Massanyi, P.; Bulla, J.; Choudhury, M.D.; Lukac, N.; Filipejova, T.; Trandzik, J.; Toman, R.; Almasiova, V. Cadmium Toxicity at Low Concentration on Rabbit Spermatozoa Motility, Morphology and Membrane Integrity In Vitro. J. Environ. Sci. Health Part A 2010, 45, 1374–1383. [Google Scholar] [CrossRef]
  95. Saintilnord, W.N.; Tenlep, S.Y.N.; Preston, J.D.; Duregon, E.; DeRouchey, J.E.; Unrine, J.M.; de Cabo, R.; Pearson, K.J.; Fondufe-Mittendorf, Y.N. Chronic Exposure to Cadmium Induces Differential Methylation in Mice Spermatozoa. Toxicol. Sci. 2021. [Google Scholar] [CrossRef]
  96. Etemadi, T.; Momeni, H.R.; Ghafarizadeh, A.A. Impact of Silymarin on Cadmium-induced Apoptosis in Human Spermatozoa. Andrologia 2020, 52, e13795. [Google Scholar] [CrossRef]
  97. Kelainy, E.G.; Laila, I.M.I.; Ibrahim, S.R. The Effect of Ferulic Acid against Lead-Induced Oxidative Stress and DNA Damage in Kidney and Testes of Rats. Environ. Sci. Pollut. Res. 2019, 26, 31675–31684. [Google Scholar] [CrossRef] [PubMed]
  98. Elsheikh, N.A.H.; Omer, N.A.; Yi-Ru, W.; Mei-Qian, K.; Ilyas, A.; Abdurahim, Y.; Wang, G. Protective Effect of Betaine against Lead-induced Testicular Toxicity in Male Mice. Andrologia 2020, 52, e13600. [Google Scholar] [CrossRef]
  99. Ezejiofor, A.N.; Orisakwe, O.E. The Protective Effect of Costus Afer Ker Gawl Aqueous Leaf Extract on Lead-Induced Reproductive Changes in Male Albino Wistar Rats. JBRA Assist. Reprod. 2019, 23, 215. [Google Scholar] [CrossRef]
  100. Hassan, E.; El-Neweshy, M.; Hassan, M.; Noreldin, A. Thymoquinone Attenuates Testicular and Spermotoxicity Following Subchronic Lead Exposure in Male Rats: Possible Mechanisms Are Involved. Life Sci. 2019, 230, 132–140. [Google Scholar] [CrossRef] [PubMed]
  101. Santhoshkumar, R. Protective Effect of Abutilon Indicum against Lead-Induced Reproductive Toxicity in Male Wistar Rats. J. Cell. Biochem. 2019, 120, 11196–11205. [Google Scholar] [CrossRef]
  102. Ghaffari, M.A.; Motlagh, B. In Vitro Effect of Lead, Silver, Tin, Mercury, Indium and Bismuth on Human Sperm Creatine Kinase Activity: A Presumable Mechanism for Men Infertility. Iran. Biomed. J. 2011, 15, 38–43. [Google Scholar]
  103. Marchlewicz, M.; Michalska, T.; Wiszniewska, B. Detection of Lead-Induced Oxidative Stress in the Rat Epididymis by Chemiluminescence. Chemosphere 2004, 57, 1553–1562. [Google Scholar] [CrossRef] [PubMed]
  104. Gandhi, J.; Hernandez, R.J.; Chen, A.; Smith, N.L.; Sheynkin, Y.R.; Joshi, G.; Khan, S.A. Impaired Hypothalamic-Pituitary-Testicular Axis Activity, Spermatogenesis, and Sperm Function Promote Infertility in Males with Lead Poisoning. Zygote 2017, 25, 103–110. [Google Scholar] [CrossRef]
  105. Fahim, M.A.; Tariq, S.; Adeghate, E. Vitamin E Modifies the Ultrastructure of Testis and Epididymis in Mice Exposed to Lead Intoxication. Ann. Anat. Anat. Anzeiger 2013, 195, 272–277. [Google Scholar] [CrossRef]
  106. Li, C.; Zhao, K.; Zhang, H.; Liu, L.; Xiong, F.; Wang, K.; Chen, B. Lead Exposure Reduces Sperm Quality and DNA Integrity in Mice. Environ. Toxicol. 2018, 33, 594–602. [Google Scholar] [CrossRef]
  107. Wirenviona, R.; I’tishom, R.; Khaerunnisa, S.; Riris, A.A.I.D.C.; Susanti, N.F.; Wahidah, N.J.; Kustantina, A.Z. Solanum Betaceum Extract as a Protective on Spermatozoa Morphology of Mice Exposed to Lead Acetate. Qanun Med. J. Fac. Med. Muhammadiyah Surabaya 2021, 5, 87–94. [Google Scholar]
  108. Kandemir, F.M.; Caglayan, C.; Aksu, E.H.; Yildirim, S.; Kucukler, S.; Gur, C.; Eser, G. Protective Effect of Rutin on Mercuric Chloride-induced Reproductive Damage in Male Rats. Andrologia 2020, 52, e13524. [Google Scholar] [CrossRef] [PubMed]
  109. Almeer, R.S.; Albasher, G.; Kassab, R.B.; Ibrahim, S.R.; Alotibi, F.; Alarifi, S.; Ali, D.; Alkahtani, S.; Moneim, A.E.A. Ziziphus Spina-Christi Leaf Extract Attenuates Mercury Chloride-Induced Testicular Dysfunction in Rats. Environ. Sci. Pollut. Res. 2020, 27, 3401–3412. [Google Scholar] [CrossRef] [PubMed]
  110. Adelakun, S.A.; Ukwenya, V.O.; Akingbade, G.T.; Omotoso, O.D.; Aniah, J.A. Interventions of Aqueous Extract of Solanum Melongena Fruits (Garden Eggs) on Mercury Chloride Induced Testicular Toxicity in Adult Male Wistar Rats. Biomed. J. 2020, 43, 174–182. [Google Scholar] [CrossRef]
  111. Fadda, L.M.; Alhusaini, A.M.; Al-Qahtani, Q.H.; Ali, H.M.; Hasan, I.H. Role of A-tocopherol and Lactobacillus Plantarum in the Alleviation of Mercuric Chloride-induced Testicular Atrophy in Rat’s Model: Implication of Molecular Mechanisms. J. Biochem. Mol. Toxicol. 2020, 34, e22481. [Google Scholar] [CrossRef]
  112. Massanyi, P.; Lukac, N.; Slivkova, J.; Kovacik, J.; Makarevich, A.V.; Chrenek, P.; Toman, R.; Forgacs, Z.; Somosy, Z.; Stawarz, R. Mercury-Induced Alterations in Rat Kidneys and Testes In Vivo. J. Environ. Sci. Health Part A 2007, 42, 865–870. [Google Scholar] [CrossRef]
  113. Mohammadi, S.; Gholamin, M.; Mohammadi, M.; Mansouri, A.; Mahmoodian, R.; Attari, S.; Kebriaei, S.M.; Zibaei, B.; Roshanaei, M.; Daneshvar, F.; et al. Down-Regulation of CatSper 1 and CatSper 2 Genes by Lead and Mercury. Environ. Toxicol. Pharmacol. 2018, 59, 82–86. [Google Scholar] [CrossRef] [Green Version]
  114. Hess, R.A. Disruption of Estrogen Receptor Signaling and Similar Pathways in the Efferent Ductules and Initial Segment of the Epididymis. Spermatogenesis 2014, 4, e979103. [Google Scholar] [CrossRef] [Green Version]
  115. Rizzetti, D.A.; Martinez, C.S.; Escobar, A.G.; da Silva, T.M.; Uranga-Ocio, J.A.; Peçanha, F.M.; Vassallo, D.V.; Castro, M.M.; Wiggers, G.A. Egg White-Derived Peptides Prevent Male Reproductive Dysfunction Induced by Mercury in Rats. Food Chem. Toxicol. 2017, 100, 253–264. [Google Scholar] [CrossRef] [PubMed]
  116. Hayati, A.; Wulansari, E.; Armando, D.S.; Sofiyanti, A.; Amin, M.H.F.; Pramudya, M. Effects of in Vitro Exposure of Mercury on Sperm Quality and Fertility of Tropical Fish Cyprinus carpio L. Egypt. J. Aquat. Res. 2019, 45, 189–195. [Google Scholar] [CrossRef]
  117. Lu, Z.; Ma, Y.; Gao, L.; Li, Y.; Li, Q.; Qiang, M. Urine Mercury Levels Correlate with DNA Methylation of Imprinting Gene H19 in the Sperm of Reproductive-Aged Men. PLoS ONE 2018, 13, e0196314. [Google Scholar] [CrossRef] [PubMed] [Green Version]
  118. Hatef, A.; Alavi, S.M.H.; Butts, I.A.E.; Policar, T.; Linhart, O. Mechanism of Action of Mercury on Sperm Morphology, Adenosine Triphosphate Content, and Motility in Perca fluviatilis (Percidae; Teleostei). Environ. Toxicol. Chem. 2011, 30, 905–914. [Google Scholar] [CrossRef]
  119. Silva, E.F.D.S.J.D.; Missio, D.; Martinez, C.S.; Vassallo, D.V.; Peçanha, F.M.; Leivas, F.G.; Brum, D.D.S.; Wiggers, G.A. Mercury at Environmental Relevant Levels Affects Spermatozoa Function and Fertility Capacity in Bovine Sperm. J. Toxicol. Environ. Health Part A 2019, 82, 268–278. [Google Scholar] [CrossRef]
  120. Zoeller, R.T.; Bergman, Å.; Becher, G.; Bjerregaard, P.; Bornman, R.; Brandt, I.; Iguchi, T.; Jobling, S.; Kidd, K.A.; Kortenkamp, A.; et al. A Path Forward in the Debate over Health Impacts of Endocrine Disrupting Chemicals. Environ. Health 2014, 13, 118. [Google Scholar] [CrossRef] [Green Version]
  121. BE, E. How Many Chemicals Are in Use Today? Chem. Eng. News 2017, 95, 23–24. [Google Scholar]
  122. Diamanti-Kandarakis, E.; Bourguignon, J.-P.; Giudice, L.C.; Hauser, R.; Prins, G.S.; Soto, A.M.; Zoeller, R.T.; Gore, A.C. Endocrine-Disrupting Chemicals: An Endocrine Society Scientific Statement. Endocr. Rev. 2009, 30, 293–342. [Google Scholar] [CrossRef]
  123. Wagner, M.; Oehlmann, J. Endocrine Disruptors in Bottled Mineral Water: Total Estrogenic Burden and Migration from Plastic Bottles. Environ. Sci. Pollut. Res. 2009, 16, 278–286. [Google Scholar] [CrossRef] [Green Version]
  124. Lee, H.R.; Jeung, E.B.; Cho, M.H.; Kim, T.H.; Leung, P.C.K.; Choi, K.C. Molecular Mechanism(s) of Endocrine-Disrupting Chemicals and Their Potent Oestrogenicity in Diverse Cells and Tissues That Express Oestrogen Receptors. J. Cell. Mol. Med. 2013, 17, 1–11. [Google Scholar] [CrossRef] [PubMed]
  125. Chalubinski, M.; Kowalski, M.L. Endocrine Disrupters—Potential Modulators of the Immune System and Allergic Response. Allergy Eur. J. Allergy Clin. Immunol. 2006, 61, 1326–1335. [Google Scholar] [CrossRef]
  126. Yawer, A.; Sychrová, E.; Labohá, P.; Raška, J.; Jambor, T.; Babica, P.; Sovadinová, I. Endocrine-Disrupting Chemicals Rapidly Affect Intercellular Signaling in Leydig Cells. Toxicol. Appl. Pharmacol. 2020, 404, 115177. [Google Scholar] [CrossRef] [PubMed]
  127. Jambor, T.; Jana, B.; Hana, G.; Eva, T.; Norbert, L. Male Reproduction: One of the Primary Targets of Bisphenol. Bisphenol. A Expo. Health Risks 2017, 27, 313–320. [Google Scholar]
  128. Makene, V.W.; Pool, E.J. The Effects of Endocrine Disrupting Chemicals on Biomarkers of Inflammation Produced by Lipopolysaccharide Stimulated RAW264.7 Macrophages. Int. J. Environ. Res. Public Health 2019, 16, 2914. [Google Scholar] [CrossRef] [Green Version]
  129. Nilsson, R. Endocrine Modulators in the Food Chain and Environment. Toxicol. Pathol. 2000, 28, 420–431. [Google Scholar] [CrossRef] [PubMed]
  130. Gálvez-Ontiveros, Y.; Páez, S.; Monteagudo, C.; Rivas, A. Endocrine Disruptors in Food: Impact on Gut Microbiota and Metabolic Diseases. Nutrients 2020, 12, 1158. [Google Scholar] [CrossRef] [PubMed]
  131. Combarnous, Y. Endocrine Disruptor Compounds (EDCs) and Agriculture: The Case of Pesticides. C. R. Biol. 2017, 340, 406–409. [Google Scholar] [CrossRef] [PubMed]
  132. McCarthy, A.R.; Thomson, B.M.; Shaw, I.C.; Abell, A.D. Estrogenicity of Pyrethroid Insecticide Metabolites. J. Environ. Monit. 2006, 8, 197–202. [Google Scholar] [CrossRef] [PubMed]
  133. Kolpin, D.W.; Thurman, E.M.; Linhart, S.M. Finding Minimal Herbicide Concentrations in Ground Water? Try Looking for Their Degradates. Sci. Total Environ. 2000, 248, 115–122. [Google Scholar] [CrossRef]
  134. Cooper, J.; Dobson, H. The Benefits of Pesticides to Mankind and the Environment. Crop. Prot. 2007, 26, 1337–1348. [Google Scholar] [CrossRef]
  135. Crépet, A.; Héraud, F.; Béchaux, C.; Gouze, M.E.; Pierlot, S.; Fastier, A.; Leblanc, J.C.; Le Hégarat, L.; Takakura, N.; Fessard, V.; et al. The PERICLES Research Program: An Integrated Approach to Characterize the Combined Effects of Mixtures of Pesticide Residues to Which the French Population Is Exposed. Toxicology 2013, 313, 83–93. [Google Scholar] [CrossRef] [PubMed]
  136. Bishop, P.L.; Willett, C.E. The Use and Acceptance of Other Scientifically Relevant Information (OSRI) in the U.S. Environmental Protection Agency (EPA) Endocrine Disruptor Screening Program. Birth Defects Res. Part B Dev. Reprod. Toxicol. 2014, 101, 3–22. [Google Scholar] [CrossRef]
  137. Jambor, T.; Greifova, H.; Kovacik, A.; Kovacikova, E.; Tvrda, E.; Forgacs, Z.; Massanyi, P.; Lukac, N. Parallel Effect of 4-Octylphenol and Cyclic Adenosine Monophosphate (CAMP) Alters Steroidogenesis, Cell Viability and ROS Production in Mice Leydig Cells. Chemosphere 2018, 199, 747–754. [Google Scholar] [CrossRef] [PubMed]
  138. Cheng, C.Y.; Mruk, D.D. The Blood-Testis Barrier and Its Implications for Male Contraception. Pharmacol. Rev. 2012, 64, 16–64. [Google Scholar] [CrossRef] [Green Version]
  139. Mruk, D.D.; Cheng, C.Y. The Mammalian Blood-Testis Barrier: Its Biology and Regulation. Endocr. Rev. 2015, 36, 564–591. [Google Scholar] [CrossRef] [PubMed]
  140. Agarwal, A.; Desai, N.R.; Makker, K.; Varghese, A.; Mouradi, R.; Sabanegh, E.; Sharma, R. Effects of Radiofrequency Electromagnetic Waves (RF-EMW) from Cellular Phones on Human Ejaculated Semen: An in Vitro Pilot Study. Fertil. Steril. 2009, 92, 1318–1325. [Google Scholar] [CrossRef] [PubMed]
  141. Kesari, K.K.; Behari, J. Evidence for Mobile Phone Radiation Exposure Effects on Reproductive Pattern of Male Rats: Role of ROS. Electromagn. Biol. Med. 2012, 31, 213–222. [Google Scholar] [CrossRef] [PubMed]
  142. Kesari, K.K.; Agarwal, A.; Henkel, R. Radiations and Male Fertility. Reprod. Biol. Endocrinol. 2018, 16, 118. [Google Scholar] [CrossRef] [Green Version]
  143. Zheng, W.; Pan, S.; Wang, G.; Wang, Y.J.; Liu, Q.; Gu, J.; Yuan, Y.; Liu, X.Z.; Liu, Z.P.; Bian, J.C. Zearalenone Impairs the Male Reproductive System Functions via Inducing Structural and Functional Alterations of Sertoli Cells. Environ. Toxicol. Pharmacol. 2016, 42, 146–155. [Google Scholar] [CrossRef] [PubMed]
  144. Gregory, M.; Cyr, D.G. The Blood-Epididymis Barrier and Inflammation. Spermatogenesis 2014, 4, e979619. [Google Scholar] [CrossRef] [PubMed] [Green Version]
  145. Li, N.; Hou, Y.; Ma, D.; Jing, W.; Dahms, H.-U.; Wang, L. Lead Accumulation, Oxidative Damage and Histopathological Alteration in Testes and Accessory Glands of Freshwater Crab, Sinopotamon Henanense, Induced by Acute Lead Exposure. Ecotoxicol. Environ. Saf. 2015, 117, 20–27. [Google Scholar] [CrossRef] [PubMed]
  146. Lukáč, N.; Massányi, P.; Kročková, J.; Naď, P.; Slamečka, J.; Ondruška, Ľ.; Formicki, G.; Trandžík, J. Relationship between trace element concentrations and spermatozoa quality in rabbit semen. Slovak J. Anim. Sci. 2009, 42, 46–50. [Google Scholar]
  147. Greifová, H.; Jambor, T.; Tokárová, K.; Speváková, I.; Knížatová, N.; Lukáč, N. Resveratrol Attenuates Hydrogen Peroxide-Induced Oxidative Stress in TM3 Leydig Cells in Vitro. J. Environ. Sci. Health Part A 2020, 55, 585–595. [Google Scholar] [CrossRef] [PubMed]
  148. Yilmaz, B.; Terekeci, H.; Sandal, S.; Kelestimur, F. Endocrine Disrupting Chemicals: Exposure, Effects on Human Health, Mechanism of Action, Models for Testing and Strategies for Prevention. Rev. Endocr. Metab. Disord. 2020, 21, 127–147. [Google Scholar] [CrossRef]
  149. Iavicoli, I.; Fontana, L.; Bergamaschi, A. The Effects of Metals as Endocrine Disruptors. J. Toxicol. Environ. Health Part B 2009, 12, 206–223. [Google Scholar] [CrossRef]
  150. Mathur, P.P.; D’Cruz, S.C. The Effect of Environmental Contaminants on Testicular Function. Asian J. Androl. 2011, 13, 585–591. [Google Scholar] [CrossRef] [PubMed] [Green Version]
  151. Darley-Usmar, V.; Wiseman, H.; Halliwell, B. Nitric Oxide and Oxygen Radicals: A Question of Balance. FEBS Lett. 1995, 369, 131–135. [Google Scholar] [CrossRef] [Green Version]
  152. Ding, W.; Hudson, L.G.; Liu, K.J. Inorganic Arsenic Compounds Cause Oxidative Damage to DNA and Protein by Inducing ROS and RNS Generation in Human Keratinocytes. Mol. Cell. Biochem. 2005, 279, 105–112. [Google Scholar] [CrossRef] [PubMed]
  153. Agarwal, A.; Prabakaran, S.A. Mechanism, Measurement, and Prevention of Oxidative Stress in Male Reproductive Physiology. Indian J. Exp. Biol. 2005, 43, 963–974. [Google Scholar]
  154. Agarwal, A.; Gupta, S.; Sikka, S. The Role of Free Radicals and Antioxidants in Reproduction. Curr. Opin. Obstet. Gynecol. 2006, 18, 325–332. [Google Scholar] [CrossRef]
  155. Moskovtsev, S.I.; Willis, J.; White, J.; Mullen, J.B.M. Leukocytospermia: Relationship to Sperm Deoxyribonucleic Acid Integrity in Patients Evaluated for Male Factor Infertility. Fertil. Steril. 2007, 88, 737–740. [Google Scholar] [CrossRef]
  156. Sabeti, P.; Pourmasumi, S.; Rahiminia, T.; Akyash, F.; Talebi, A.R. Etiologies of Sperm Oxidative Stress. Int. J. Reprod. Biomed. 2016, 14, 231. [Google Scholar] [CrossRef]
  157. Griveau, J.F.; Lannou, D.L. Reactive Oxygen Species and Human Spermatozoa: Physiology and Pathology. Int. J. Androl. 1997, 20, 61–69. [Google Scholar] [CrossRef]
  158. Van Tran, L.; Malla, B.A.; Kumar, S.; Tyagi, A.K. Polyunsaturated Fatty Acids in Male Ruminant Reproduction—A Review. Asian Australasian J. Anim. Sci. 2017, 30, 622. [Google Scholar] [CrossRef] [Green Version]
  159. Sanocka, D.; Kurpisz, M. Reactive Oxygen Species and Sperm Cells. Reprod. Biol. Endocrinol. 2004, 2, 1–7. [Google Scholar] [CrossRef] [PubMed] [Green Version]
  160. Lukac, N.; Lukacova, J.; Pinto, B.; Knazicka, Z.; Tvrda, E.; Massanyi, P. The Effect of Nonylphenol on the Motility and Viability of Bovine Spermatozoa in Vitro. J. Environ. Sci. Health Part A 2013, 48, 973–979. [Google Scholar] [CrossRef]
  161. Zhang, Z.H.; Zhu, H.B.; Li, L.L.; Yu, Y.; Zhang, H.G.; Liu, R.Z. Decline of Semen Quality and Increase of Leukocytes with Cigarette Smoking in Infertile Men. Iran. J. Reprod. Med. 2013, 11, 589. [Google Scholar]
  162. Talebi, A.R.; Sarcheshmeh, A.A.; Khalili, M.A.; Tabibnejad, N. Effects of Ethanol Consumption on Chromatin Condensation and DNA Integrity of Epididymal Spermatozoa in Rat. Alcohol 2011, 45, 403–409. [Google Scholar] [CrossRef]
  163. Henkel, R.R. Leukocytes and Oxidative Stress: Dilemma for Sperm Function and Male Fertility. Asian J. Androl. 2011, 13, 43. [Google Scholar] [CrossRef] [Green Version]
  164. Zhou, Y.; Wu, H.; Huang, H. Epigenetic Effects of Male Obesity on Sperm and Offspring. J. Bio-X Res. 2018, 1, 105–110. [Google Scholar] [CrossRef]
  165. Song, J.; Gao, X.; Tang, Z.; Li, H.; Ruan, Y.; Liu, Z.; Wang, T.; Wang, S.; Liu, J.; Jiang, H. Protective Effect of Berberine on Reproductive Function and Spermatogenesis in Diabetic Rats via Inhibition of ROS/JAK2/NFκB Pathway. Andrology 2020, 8, 793–806. [Google Scholar] [CrossRef] [PubMed]
  166. Manna, I.; Jana, K.; Samanta, P.K. Effect of Different Intensities of Swimming Exercise on Testicular Oxidative Stress and Reproductive Dysfunction in Mature Male Albino Wistar Rats. Indian J Exp Biol. 2004, 42, 816–822. [Google Scholar]
  167. Eskiocak, S.; Gozen, A.S.; Taskiran, A.; Kilic, A.S.; Eskiocak, M.; Gulen, S. Effect of Psychological Stress on the L-Arginine-Nitric Oxide Pathway and Semen Quality. Braz. J. Med. Biol. Res. 2006, 39, 581–588. [Google Scholar] [CrossRef] [Green Version]
  168. Desai, N.; Sabanegh, E.; Kim, T.; Agarwal, A. Free Radical Theory of Aging: Implications in Male Infertility. Urology 2010, 75, 14–19. [Google Scholar] [CrossRef] [PubMed]
  169. Chyra-Jach, D.; Kaletka, Z.; Kasperczyk, A. The Role of Physiologically Occurring Elements in Semen and Effect of Heavy Metals on Semen. Ann. Acad. Med. Silesiensis 2020, 74, 1–13. [Google Scholar] [CrossRef]
  170. Massányi, P.; Trandžík, J.; Nad, P.; Koréneková, B.; Skalická, M.; Toman, R.; Lukáč, N.; Strapák, P.; Halo, M.; Turčan, J. Concentration of Copper, Iron, Zinc, Cadmium, Lead, and Nickel in Boar Semen and Relation to the Spermatozoa Quality. J. Environ. Sci. Health Part A 2003, 38, 2643–2651. [Google Scholar] [CrossRef]
  171. Doshi, S.B.; Khullar, K.; Sharma, R.K.; Agarwal, A. Role of Reactive Nitrogen Species in Male Infertility. Reprod. Biol. Endocrinol. 2012, 10, 109. [Google Scholar] [CrossRef] [PubMed] [Green Version]
  172. O’Flaherty, C.; Matsushita-Fournier, D. Reactive Oxygen Species and Protein Modifications in Spermatozoa. Biol. Reprod. 2017, 97, 577–585. [Google Scholar] [CrossRef] [PubMed]
  173. Aitken, R.J.; Gibb, Z.; Baker, M.A.; Drevet, J.; Gharagozloo, P. Causes and Consequences of Oxidative Stress in Alzheimer’s Disease. Free Radic. Biol. Med. 2016, 28, 1–10. [Google Scholar]
  174. Henkel, R.; Samanta, L.; Agarwal, A. Oxidants, Antioxidants, and Impact of the Oxidative Status in Male Reproduction; Elsevier Science: Amsterdam, The Netherlands, 2018. [Google Scholar]
  175. Vizzari, F.; Massányi, M.; Knížatová, N.; Corino, C.; Rossi, R.; Ondruška, Ľ.; Tirpák, F.; Halo, M.; Massányi, P. Effects of Dietary Plant Polyphenols and Seaweed Extract Mixture on Male-Rabbit Semen: Quality Traits and Antioxidant Markers. Saudi J. Biol. Sci. 2021, 28, 1017–1025. [Google Scholar] [CrossRef]
  176. Tafuri, S.; Cocchia, N.; Carotenuto, D.; Vassetti, A.; Staropoli, A.; Mastellone, V.; Peretti, V.; Ciotola, F.; Albarella, S.; Del Prete, C.; et al. Chemical Analysis of Lepidium meyenii (Maca) and Its Effects on Redox Status and on Reproductive Biology in Stallions. Molecules 2019, 24, 1981. [Google Scholar] [CrossRef] [PubMed] [Green Version]
  177. Tafuri, S.; Cocchia, N.; Vassetti, A.; Carotenuto, D.; Esposito, L.; Maruccio, L.; Avallone, L.; Ciani, F. Lepidium meyenii (Maca) in Male Reproduction. Nat. Prod. Res. 2019, 1–10. [Google Scholar] [CrossRef] [PubMed]
  178. Vizzarri, F.; Chiapparini, S.; Corino, C.; Casamassima, D.; Palazzo, M.; Parkanyi, V.; Ondruska, L.; Rossi, R. Dietary Supplementation with Natural Extracts Mixture: Effects on Reproductive Performances, Blood Biochemical and Antioxidant Parameters in Rabbit Does. Ann. Anim. Sci. 2020, 20, 565–578. [Google Scholar] [CrossRef]
  179. Halo, M., Jr.; Massányi, M.; Tokárová, K.; Tirpák, F.; Greifová, H.; Solár, D.; Halo, M.; Massányi, P. High Taurine Concentrations Negatively Effect Stallion Spermatozoa Parameters in Vitro. Acta Fytotech. Zootech. 2021, 24. [Google Scholar] [CrossRef]
  180. Vizzarri, F.; Palazzo, M.; Casamassima, D.; Ondruska, L.; Massanyi, M.; Tirpak, F.; Formicki, G.; Gren, A.; Massanyi, P. Lippia citriodora (Verbascoside) Extract Supplementation: Effect on Rabbit Semen Quality In Vivo and In Vitro. Czech. J. Anim. Sci. 2019, 64, 1–10. [Google Scholar] [CrossRef] [Green Version]
  181. Slanina, T.; Miškeje, M.; Tirpák, F.; Baszczyk, M.; Stawarz, R.; Massányi, P. Effect of Taurine on Turkey (Meleagris gallopavo) Spermatozoa Viability and Motility. Czech. J. Anim. Sci. 2018, 63, 127–135. [Google Scholar] [CrossRef] [Green Version]
  182. Tirpak, F.; Slanina, T.; Kovacik, A.; Ondruska, L.; Massanyi, P.; Halo, M.; Massanyi, P. Low Taurine Concentrations Possitively Affect Rabbit Spermatozoa Properties in Later Time Intervals. J. Microbiol. Biotechnol. Food Sci. 2017, 7, 128–131. [Google Scholar] [CrossRef] [Green Version]
  183. Tvrdá, E.; Tušimová, E.; Kováčik, A.; Paál, D.; Greifová, H.; Abdramanov, A.; Lukáč, N. Curcumin Has Protective and Antioxidant Properties on Bull Spermatozoa Subjected to Induced Oxidative Stress. Anim. Reprod. Sci. 2016, 172, 10–20. [Google Scholar] [CrossRef] [PubMed]
Table
Table 1. The effect of non-ionizing and ionizing radiation on the most targeted sites in male reproduction.
Table 1. The effect of non-ionizing and ionizing radiation on the most targeted sites in male reproduction.
RadiationThe Site of the Effect
TestisEpididymisSpermatozoa
Non-ionizing
  • dilatated and congested blood vessels in tunica albuginea and interstitium
  • degenerated spermatogenic cells
  • diminished Sertoli cells containing numerous vacuoles, swollen mitochondria, and broken organelles
  • enhanced production of cytokines by Sertoli cells
  • germ cells arrested in pre-meiotic stages
  • induced generation of ROS
[36,37,38]
  • reduced weight of epididymis
  • decreased sperm count
  • morphological defects of spermatozoa
  • increased lipid peroxidation
  • diminished content of glutathione
  • degeneration of epithelium cells
[39,40,41,42,43]
  • dose & frequency-dependent effect on motility
  • spontaneous acrosome reaction
  • sperm head malformations
  • increased DNA damage
[33,36,44,45,46]
Ionizing
  • decreased testis weight
  • damaged seminiferous tubules
  • disorganized spermatogenic cells
  • declined number of spermatocytes and spermatogonia
  • induced apoptosis of spermatogenic cells
  • degeneration of Sertoli cells
  • the high appearance of swelling mitochondria
  • extensive ROS generation
[47,48,49,50]
  • the lower weight of epididymis
  • diminished luminal diameter
  • high incidence of vacuoles in the epithelium
  • impaired spermatogenesis
  • reduced sperm count
  • elevated apoptosis
  • enhanced intracellular ROS
  • decreased level of zinc
[47,51,52,53]
  • decreased motility and viability
  • reduced sperm count
  • morphological malformations
  • elevated intracellular ROS
  • down-regulated expression of tubulin
  • decreased content of ATP
[47,49,50,51]
Table
Table 2. The effect of selected (the most harmful) heavy metals on the most targeted sites in male reproduction.
Table 2. The effect of selected (the most harmful) heavy metals on the most targeted sites in male reproduction.
Heavy MetalThe Site of the Effect
TestisEpididymisSpermatozoa
Cadmium
  • alterations in the number and structure of seminiferous tubules
  • the increased volume of stroma
  • the thinned layer of Sertoli and germ cells
  • altered spermatogenesis
[84,85,86]
  • enhanced weight of epididymis
  • thickened epithelia
  • widened interstitium
  • vacuolized Sertoli cells
  • impaired spermatogenesis
  • dilatated blood vessels
  • induced apoptosis and inflammation
  • interfered androgen production
  • increased ROS production
[87,88,89,90]
  • reduction in sperm count
  • decreased viability and motility
  • altered morphology
  • altered acrosome and mitochondrial segment
  • changed DNA methylation
[91,92,93,94,95,96]
Lead
  • reduced testis weight
  • disrupted testosterone production
  • elevated ROS
  • disorganization of seminiferous tubules
  • interfered or even absent spermatogenesis
  • enlarged spermatocytes
  • inflamed tunica albuginea
  • down-regulation of Catsper 1 and 2
[97,98,99,100,101,102]
  • decreased weight of epididymis
  • increased oxidative stress and lipid peroxidation
  • diminished epididymal spermatozoa
  • modulated enzymatic activity
  • reduced quantity of stereocilia of epithelial cells
  • lowered number of spermatozoa
[103,104,105]
  • decreased sperm count and motility
  • excessive generation of ROS
  • enhanced DNA damage
  • morphological malformations
  • decreased intracellular cAMP
  • inhibition of sperm creatine kinase
  • displacing zinc from its binding sites
[101,102,104,106,107]
Mercury
  • hypertrophy of seminiferous tubules with occlusions in the lumen
  • vacuolated areas contained in the seminiferous tubules
  • thinned tubules
  • dilatated blood vessels
  • the increased volume of the interstitium
  • degeneration and disorganization of spermatogenic cells
  • reduced number of spermatocytes
  • down-regulation of Catsper 1 and 2
  • disruption of estrogen receptor
[108,109,110,111,112,113,114]
  • reduced weight of epididymis
  • decreased sperm count
  • morphological aberrations
  • elevated levels of ROS and lipid peroxidation
  • disruption of estrogen receptor
[110,114,115]
  • reduced sperm count
  • higher incidence of immotile spermatozoa
  • the damaged plasma membrane, axoneme
  • elevated generation of ROS
  • increased lipid peroxidation
  • impaired fertilization ability
  • altered DNA methylation
  • decreased adenosine triphosphate
  • inhibition of sperm creatine kinase
[102,109,115,116,117,118,119]
Publisher’s Note: MDPI stays neutral with regard to jurisdictional claims in published maps and institutional affiliations.

Share and Cite

MDPI and ACS Style

Tirpák, F.; Greifová, H.; Lukáč, N.; Stawarz, R.; Massányi, P. Exogenous Factors Affecting the Functional Integrity of Male Reproduction. Life 2021, 11, 213. https://doi.org/10.3390/life11030213

AMA Style

Tirpák F, Greifová H, Lukáč N, Stawarz R, Massányi P. Exogenous Factors Affecting the Functional Integrity of Male Reproduction. Life. 2021; 11(3):213. https://doi.org/10.3390/life11030213

Chicago/Turabian Style

Tirpák, Filip, Hana Greifová, Norbert Lukáč, Robert Stawarz, and Peter Massányi. 2021. "Exogenous Factors Affecting the Functional Integrity of Male Reproduction" Life 11, no. 3: 213. https://doi.org/10.3390/life11030213

Note that from the first issue of 2016, this journal uses article numbers instead of page numbers. See further details here.

Article Metrics

Back to TopTop