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Review

A Scoping Review on Male-Mediated Developmental Toxicity

by
Lidia Caporossi
*,
Paola Castellano
,
Enrico Paci
and
Daniela Pigini
Department of Occupational and Environmental Medicine, Epidemiology and Hygiene, INAIL, National Institute for Insurance against Accidents at Work, 00078 Monte Porzio Catone, Italy
*
Author to whom correspondence should be addressed.
Toxics 2025, 13(9), 707; https://doi.org/10.3390/toxics13090707
Submission received: 16 July 2025 / Revised: 18 August 2025 / Accepted: 21 August 2025 / Published: 22 August 2025
(This article belongs to the Special Issue Exposure to Chemicals and Health Effects in Occupational and Everyday Settings)
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Abstract

Background: Developmental toxicity is defined as adverse effects induced either during pregnancy or as a result of parental exposure. While considerable attention has been devoted to maternal exposure to such chemicals, the role of paternal exposure has often been regarded as less significant. Objective: This study aims to highlight the impact of male-mediated developmental toxicity. Methods: An online search was conducted using PubMed, Scopus, and Google Scholar to identify studies focusing on developmental toxicity in offspring associated with paternal exposure during the preconception period. Results: The scientific literature—ranging from studies on pharmaceutical use to substances of abuse (notably tobacco, alcohol, opioids, and cannabinoids), as well as occupational and environmental exposure to specific compounds (e.g., phthalates, certain organic solvents, pesticides)—indicates that paternal exposure to developmental toxicants can adversely affect offspring health through various biochemical mechanisms. Conclusions: There is substantial experimental evidence of male-mediated developmental toxicity for various chemicals, demonstrating a particular vulnerability of the male germ line to transmissible effects. Several mechanisms have been proposed to explain the biochemical pathways underlying this toxicity. Evidence in humans is more challenging to interpret; however, numerous findings—both concerning substances of abuse and occupational exposures—raise concerns regarding the potential developmental risks to offspring.

1. Introduction

Sexual function and fertility in both adult males and females can be adversely affected by reproductive toxicity, as can the normal development of offspring through developmental toxicity.
The concept of developmental toxicity has been broadly defined in the Organization for Economic Cooperation and Development (OECD) draft Guidance Document on Reproductive Toxicity Testing and Assessment (GD 43) [1] as “…any effect that interferes with the normal development of the conceptus, either before or after birth, and resulting from exposure of either parent prior to conception, or exposure of the developing offspring during prenatal development, or postnatally, to the time of sexual maturation”.
The primary objective of classification under developmental toxicity is to provide hazard warnings to pregnant women, as well as to men and women of reproductive age.
Therefore, for practical classification purposes, developmental toxicity is essentially defined as adverse effects induced either during pregnancy or as a result of parental exposure. These effects may manifest at any stage of the organism’s lifespan. Developmental toxicity can lead to fetal death, structural abnormalities, impaired growth, and functional deficits [2].
For at least 70 years, researchers have considered the hypothesis that paternal exposure may influence offspring health [3]. Anthony Scialli [4] questioned whether the lack of unequivocal evidence of male-mediated developmental toxicity in humans reflects methodological limitations, rather than the absence of the phenomenon itself.
Pharmacological studies have contributed significantly to this debate, providing substantial evidence [5,6,7,8]. In particular, a large body of literature has addressed paternal-mediated toxicity associated with dermatological medications, including retinoids, immunosuppressants, antiandrogens, and thalidomide [6]. A review of 234 studies [5], covering 131 medications, identified 34 drugs associated with male infertility and sexual dysfunction, with 16 compounds directly implicated in concerns regarding teratogenicity. Some drugs, such as rosuvastatin [8], sevoflurane [9], and cyclophosphamide [10,11], are supported by experimental data demonstrating that paternal exposure can impair offspring health. Others, such as selective serotonin reuptake inhibitors (SSRIs), have shown certain adverse effects in humans, including increased risks of preterm birth [7], a mild increase in autism spectrum disorder risk in a cohort of 669 parents and 922 children [12], and a higher incidence of attention deficit hyperactivity disorder (ADHD) in offspring, as observed in a population of 781,470 subjects [13]. In all these studies, the fathers had to have taken the drugs at least 3 months before conception.
The question of how paternal exposure affects offspring health has become increasingly important, particularly given that men are generally subject to higher levels of potentially harmful occupational exposures compared to women [14]. Furthermore, the element of paternal age and the level of exposure can influence, even significantly, the toxic effects that can be recorded; in fact, higher male age is associated with a range of adverse health outcomes [15,16]. Public concern regarding environmental chemicals has been amplified by the growing understanding of epigenetic mechanisms at the molecular level [17,18,19], alongside an increasing number of studies addressing the multigenerational and transgenerational effects of environmental chemicals and lifestyle-related factors. To fully elucidate parent–child transmission effects, close collaboration between basic science and epidemiological research is essential [20].
In Europe, Directive (EU) 2022/431 [21] has aligned workplace risk management measures for substances toxic for reproduction with those established for carcinogenic and mutagenic substances, adopting a more precautionary approach for both male and female workers. In light of current regulations, some companies are beginning to question whether workplace exposure to substances harmful solely to fetal development should be addressed more broadly, rather than focusing exclusively on the protection of pregnant women. The legislation makes no distinction regarding the prevention and protection measures to be implemented in the case of reproductive toxicity affecting the fetus, nor does it differentiate between male and female workers. In fact, the answer to this concern is already implicit in the definition of developmental toxicants, which, unfortunately, is still too often overlooked with respect to paternal exposure.
However, the biochemical mechanisms underlying male-mediated developmental toxicity remain to some extent to be clarified, as does the identification of the chemical substances most frequently implicated in this phenomenon according to the scientific literature. This scoping review was aimed at mapping scientific evidence available in this field in a systematic way. The formulated research question was: What does the scientific literature report regarding paternal exposure to developmental toxicants during the preconception period and the potential adverse effects on offspring?

2. Methods

The present scoping review was conducted following the Preferred Reporting Items for Systematic Reviews and Meta-Analyses extension for Scoping Reviews (PRISMA-ScR) checklist [22]. The PRISMA checklist for scoping review is available as a Supplementary File.

2.1. Information Sources and Literature Search

A bibliographic search was performed from June to July 2025 using the Scopus, PubMed, and Google Scholar databases, employing the keywords “paternal exposure” and “developmental toxicity” or “male exposure” and “fetal toxicity.”

2.2. Inclusion Criteria

Articles, papers, books, and reports were included if they evaluated, compared, used, or described a situation of chemical exposure of men and related effects on offsprings. The types of chemicals had to be identified and the effects on the fetus or child had to be described.
Studies published in languages other than English, Italian, French, or Spanish were excluded. Articles documenting developmental toxicity solely in the context of maternal exposure were also excluded. Only studies investigating paternal preconception exposure leading to adverse developmental outcomes in offspring were included. In cases where both maternal and paternal exposures were assessed, the studies were excluded to avoid possible confounding factors. Grey literature was not considered. Surveys produced over the last thirty years have been collected
The scoping review is concentrated on epidemiological investigations in human populations. Investigations focused on the effects due to the taking of drugs by fathers were excluded, as the type of “exposure” is linked to clinical needs, so considerations regarding the risk–benefit balance are the responsibility of the treating doctor. Instead, this scoping review wanted to focus on investigations in which exposure to chemical substances is essentially linked to work or specific living conditions. In particular, for investigations on occupational exposures, cohort studies were collected in which groups of those exposed and non-exposed were compared, or case/control investigations, in which the recruitment was conducted starting from the diagnoses of children, and therefore, the professional exposure was characterized retrospectively (also through a job exposure matrix).

2.3. Screening Process

The screening and data extraction processes of 4 reviewers were refined as they screened the same set of publications and discussed the results. The titles, abstracts, and full texts of the identified studies were rated sequentially by four researchers who worked in pairs. Discussion led to a consensus that resolved any disagreements about study selection and data collection, with additional reviewers if necessary.
A data-charting form was collaboratively developed by the four reviewers to define the variables to be extracted. Each researcher independently charted the data, after which the results were discussed, and the data-charting form was continuously updated.
Data abstracted included paper characteristics, with particular focus on the type of chemical exposure (occupational, environmental, substance abuse, or lifestyle-related). Experimental animal studies were included solely to illustrate proposed biochemical mechanisms.
A schematic overview of the search strategy and the selected articles is presented in Figure 1.

3. Possible Biological Mechanisms

In vitro studies have already suggested that paternal exposure plays a significant role in fetal development. For example, an investigation into exposure to di-n-butyl phthalate [23] demonstrated that paternal exposure resulted in delayed sexual maturation in female offspring and a decline in seminal fluid quality in the male F1 generation. Similarly, studies on lead exposure [24] not only reported a reduction in seminal fluid quality in male rats but also observed a significant increase in pregnancy loss in females mated with these males.
There are multiple mechanisms through which paternal exposure to chemicals can influence conception outcomes [25,26].
  • Exposure to toxic contaminants in seminal fluid may directly affect the ovum or embryo. The blood–testis barrier is broken by many industrial chemicals, which can be detected in seminal plasma [27]. However, the real significance of this pathway remains unclear. In vitro fertilization assays could be useful to understand this pathway of toxicity; for instance, some studies [28] have reported that paternal exposure to certain chemicals, such as flame retardants, is associated with impaired fertilization of the oocyte.
  • Direct DNA damage in the germ line can be caused by chemicals, particularly affecting spermatogonia (point mutations), spermatocytes (aneuploidy), and spermatids (DNA strand breaks and chromosomal aberrations) [29]. Considering that a sperm cell’s ability to repair DNA fades during the last stage of spermatogenesis, it is not surprising that these effects have been demonstrated for many chemicals [26].
  • Development in subsequent generations may be directly or indirectly affected by paternal chemical exposure through interference with gene expression via imprinting and disruption of the epigenome. A proposed molecular mechanism involves DNA methylation, typically occurring at cytosine residues adjacent to guanine (CpG sites) [30], which can lead to the silencing of gene transcription in specific genomic regions. Another suggested mechanism is histone modification [17,31]. Although the replacement of most histones by smaller protamines occurs during spermatogenesis, approximately 5 to 10% of human histones persist in the sperm nucleus and remain unaltered [32,33]. Consequently, these histone modifications can be transmitted through spermatozoa. For example, paternal exposure to valproic acid in mice has been shown to induce behavioral deficits such as decreased social interaction, impaired pre-pulse inhibition, and non-spatial memory deficits. These effects have been linked to altered acetylation of histone H3 in the prefrontal cortex and hippocampus of the offspring [34].
  • Noncoding RNAs in seminal plasma are also suspected to play a role in transmitting paternal epigenetic information to offspring. Several small noncoding RNAs, as well as a limited number of mRNAs, have been shown to persist in sperm and enter the oocyte upon fertilization [35,36,37].
Offspring may exhibit a variety of intergenerational and transgenerational inherited effects resulting from exposure to numerous chemicals, including both bio-persistent and rapidly metabolized endocrine-disrupting compounds [18,19,38].
Environmental factors can impact offspring health through the paternal germ line, as supported by an increasing body of experimental evidence [39], although further biochemical research is necessary to fully elucidate the underlying pathways.

4. Evidence About Substances of Abuse: Alcohol, Tobacco Smoke, Opioids, Cannabis

The earliest and most evident effects reported in the scientific literature regarding male-mediated developmental toxicity involve substances of abuse, particularly alcohol, tobacco, opioids, and cannabis [40]. In these cases, the exposure levels and routes were well characterized, enabling a clear correlation to be established between paternal substance abuse and adverse developmental outcomes in offspring.
Numerous studies have demonstrated that substances of abuse can impair spermatogenesis and disrupt sexual hormone secretion via the hypothalamic–pituitary axis, thereby affecting sexual function [41,42,43]. Further proof shows that if paternal exposure to these substances occurs during preconception (at least three months before conception), it can lead to negative outcomes for the offspring. A summary of the effects associated with major substances of abuse is presented in Table 1. Specifically, paternal preconception exposure to tobacco smoke, alcohol, opioids, or cannabis smoke has been linked to neurodevelopmental impairments in offspring, including reduced mental health, hyperactivity, depression, attention deficits, and attention deficit hyperactivity disorder (ADHD) [44,45], likely mediated by epigenetic mechanisms [46,47,48,49,50].
Increased morbidity in offspring may manifest in both the short term (neonatal period and infancy) and long term (from childhood through adulthood).

5. Occupational and Environmental Exposure

Since the early 2000s, evidence has emerged indicating a decline in male seminal fluid quality, particularly in more polluted geographic regions, leading to the hypothesis that exposure to environmental pollutants adversely affects male reproductive health [76]. These areas have also reported higher incidences of stillbirth, certain fetal malformations, and spontaneous abortions, although a definitive causal correlation remains a subject of debate [77].
Conversely, studies conducted in occupational settings provide stronger evidence and clearer associations. An early systematic review from 1994 [78] classified the risk of spontaneous abortions or birth defects associated with male occupational exposure as “strong” for mercury and anesthetic gases, “moderate” for lead and organic solvents, and “limited” for pesticides. Subsequently, more methodologically robust studies have investigated solvent exposure in the painting industry, reporting increased risks of birth defects (OR = 1.86, 95% CI 1.4–2.5 [78]; and OR = 6.2, 95% CI 1.4–28 [79]).
A meta-analysis [80] highlighted how paternal exposure to solvents can be linked to a greater onset of neural tube defects (OR = 1.86, 95% CI 1.40–2.46) and anencephaly (OR = 2.18, 95% CI 1.52–3.11), while a weak correlation (RR = 1.19, 95% CI 1.00–1.41) between paternal exposure to some pesticides and the risk of hypospadias emerged. For spina bifida and solvent exposure, even with an OR higher than 1, the significance was lacking (OR = 1.59, 95% CI 0.99–2.56).
In contrast, another study [81] investigating the relationship between paternal pesticide exposure and cryptorchidism in offspring found no statistically significant association (OR = 1.04, 95% CI 0.96–1.12).
Positive associations were also reported between paternal occupational exposure to phthalates and polychlorinated compounds and the occurrence of congenital heart defects (OR = 2.08, 95% CI 1.27–3.40). Notably, specific subtypes of congenital heart defects showed stronger correlations: exposure to phthalates was linked to an increased risk of perimembranous ventricular septal defect (OR = 2.84, 95% CI 1.37–5.92), exposure to bisphenols with atrioventricular septal defects (OR = 4.22, 95% CI 1.23–14.42), and paternal exposure to alkylphenols was associated with coarctation of the aorta (OR = 3.85, 95% CI 1.17–12.67) [82].
A large cohort study [83], conducted between 1952 and 1988, enrolled 19,675 children born to 9512 fathers to assess the impact of paternal occupational exposure to chlorophenols—used as wood preservatives—on fetal malformations. Offspring of sawmill workers were the most affected by congenital malformations. Specifically, paternal exposure during the three months prior to conception was associated with an increased risk of eye malformations (OR = 2.87, 95% CI 1.5–5.5) and cataracts (OR = 5.68, 95% CI 1.4–22.6). No statistically significant associations were observed for undescended testes (OR = 1.16, 95% CI 0.8–1.6), genital malformations in general (OR = 1.29, 95% CI 0.9–1.5), or spina bifida (OR = 1.32, 95% CI 0.2–2.1). Another study [83] reported an increased risk of cleft lip in offspring of male farmers exposed to pesticides (OR = 3.00, 95% CI 1.03–8.70). However, the small sample size (35 cases and 35 controls) limits the strength of this finding.
A summary of the literature regarding occupational paternal exposure and pregnancy outcomes is presented in Table 2.

6. Conclusions

In this scoping review, we identified 47 primary studies focusing on dissemination and implementation research related to male-mediated developmental toxicity, encompassing both daily habits and occupational or environmental exposures.
More than half of the investigations concern substances of abuse, in which the levels of exposure, in terms of concentration and frequency, are certainly high and therefore have made it possible over the years to highlight effects, also for the development of conceived children, with greater clarity. Tobacco smoke, opioids, cannabis, and alcohol are mainly involved in this group of substances. The duration of substance abuse could be an important parameter, from a toxicological point of view, that is not always collected by the investigated subjects, which we think could be a limitation of some studies and a need for its introduction into future research. Similarly, considerations regarding the father’s age should always be taken into account as a confounding factor in epidemiological investigations.
On the other hand, the investigations conducted on working populations have focused attention on specific contexts (the production and use of paints, treatment of wooden materials, plastic industry) in which the use of specific chemical products is probably quantitatively consistent.
Our findings indicate that, particularly for certain chemicals, substantial evidence exists linking paternal preconception exposure to adverse effects in offspring.
There is robust experimental evidence demonstrating male-mediated developmental toxicity for numerous chemicals, highlighting a particular sensitivity of the male germ line to potentially transmissible effects. Several mechanisms have been proposed that may clarify the underlying biochemical pathways of toxicity. From a risk assessment perspective, it will be important for future research to focus on identifying a dose–response relationship, in order to allow for appropriate risk prevention measures.
Although human data are often complex and difficult to interpret, current scientific findings raise concerns about potential risks to offspring development arising from both paternal drug abuse (e.g., narcotics) and occupational chemical exposures.
When discussing reproductive health and embryonic development, the focus is often primarily on the mother. However, in recent years, increasing attention has been directed towards the paternal role, particularly concerning environmental and occupational exposures that can impact offspring health even before conception.
Unfortunately, too often, the protection of workers potentially exposed to endocrine disruptors has been, and still is, limited to women and strictly to the pregnancy period, without considering the long-term effects on fertility and possible genetic damage to and epigenetic effects on future pregnancies. Moreover, little attention is paid to the effects on men and the role that potential exposure to toxic or reprotoxic substances could have on future conception.
Organic solvents, pesticides, and substances such as alcohol, tobacco, and drugs are known to disrupt spermatogenesis and alter epigenetic mechanisms. While these exposures may not produce overt symptoms in adult men, they can induce lasting changes in the germ cells that give rise to sperm. Genetic or epigenetic modifications at this level can be transmitted to offspring, potentially influencing their development, metabolism, fertility, and susceptibility to diseases in adulthood.
Our scoping review has several limitations. First, studies addressing male-mediated developmental toxicity using in vitro and in vivo approaches were excluded by design. While this was an intentional eligibility criterion, it may have resulted in the omission of valuable information on certain chemicals. Second, the exclusion of publications not written in English, Italian, Spanish, or French limits our ability to capture evidence from studies published in other languages, potentially introducing a geographical bias. Lastly, we did not register our scoping review protocol. Although we do not view this oversight as a study limitation, per se, protocol registration is considered as best practice [86].
It is essential to develop prevention policies that recognize this risk and adopt appropriate preventive and protective measures, including the use of personal protective equipment, environmental controls, worker training, and, where possible, substitution of hazardous substances. As reported in the previous paragraphs, paternal exposure to chemical substances can significantly impact the health of the unborn child, underscoring the crucial role of the father—particularly in relation to environmental and toxicological factors that affect spermatogenesis and germline epigenetics. Therefore, it is essential to educate and inform prospective fathers about the potential risks associated with paternal exposure and its effects on offspring, especially since male-focused prevention is often overlooked in educational, healthcare, and informational programs. Preconception preventive efforts not only enhance reproductive health but also contribute to reducing the risk of chronic diseases in future generations.
Therefore, given the importance placed by the new Directive 2022/431 on protection from reprotoxic substances, it is advisable that occupational regulations extend protection to both sexes and, for women, not limit it solely to the pregnancy period.

Supplementary Materials

The following supporting information can be downloaded at: https://www.mdpi.com/article/10.3390/toxics13090707/s1, File S1: Reporting Items for Systematic reviews and Meta-Analyses extension for Scoping Reviews (PRISMA-ScR) Checklist.

Author Contributions

Conceptualization, L.C.; methodology, L.C.; data curation, L.C., E.P., P.C. and D.P.; writing—original draft preparation, L.C.; writing—review and editing, D.P., P.C., and E.P.; visualization, L.C., E.P., P.C. and D.P. All authors have read and agreed to the published version of the manuscript.

Funding

This research received no external funding.

Data Availability Statement

No new data were created or analyzed in this study.

Conflicts of Interest

The authors declare no conflicts of interest.

Abbreviations

The following abbreviations are used in this manuscript:
LHLuteinizing hormone
FSHFollicle-stimulating hormone;
DNADeoxyribonucleic acid
THC∆9-Tetrahydrocannabinol; 5GRH- Growth hormone-releasing hormone
OROdds ratio
CIConfidence interval

References

  1. Organization for Economic Cooperation and Development—OECD. Series on testing and assessment, number 43. In Guidance Document on Mammalian Reproductive Toxicity Testing and Assessment; ENV/JM/MONO 16; OECD: Paris, France, 2008. [Google Scholar]
  2. Hass, U. The need for developmental neurotoxicity studies in risk assessment for developmental toxicity. Reprod. Toxicol. 2006, 22, 148–156. [Google Scholar] [CrossRef] [PubMed]
  3. Ellekilde Bonde, J.P.; Søgaard Tøttenborg, S.; Sørig Hougaard, K. Paternal environmental exposure and offspring health. Curr. Opin. Endocr. Metab. Res. 2019, 7, 14–20. [Google Scholar] [CrossRef]
  4. Scialli, A.R. Paternally mediated effects and political correctness. Reprod. Toxicol. 1993, 7, 189–190. [Google Scholar] [CrossRef] [PubMed]
  5. Hui, E.X.W.; Huang, X.; Oon, H.H. Review of dermatologic medications and impact on male fertility, sexual dysfunction and teratogenicity. Andrology 2022, 10, 1272–1285. [Google Scholar] [CrossRef]
  6. Kumar, P.; Das, A.; Lal, N.R.; Jain, S.; Ghosh, A. Safety of important dermatological drugs (retinoids, immune suppressants, anti androgens and thalidomide) in reproductively active males with respect to pregnancy outcome: A brief review of literature. Indian J. Dermatol Vener. Vener. Leprol 2018, 84, 539–546. [Google Scholar] [CrossRef]
  7. Garvik, O.S.; Jølving, L.R.; Lund, K.; Friedman, S.; Nørgård, B.M. Paternal use of selective serotonin reuptake inhibitors and adverse health outcomes: A nationwide cohort study on 13,547 exposed children. Andrology 2025, 13, 259–267. [Google Scholar] [CrossRef]
  8. De Mello, T.F.; Goedert, A.B.; Sengl de Souza, J.S.; da Cruz, J.V.R.; Santos da Silva, A.; Knorst, J.K.; Muller, Y.M.R.; Barreto Silva, F.R.M.; Araujo Leite, G.A. Prolonged exposure to rosuvastatin from pre-puberty to adulthood impairs sperm quality in mice and leads to paternally mediated developmental toxicity. Reprod. Toxicol. 2024, 130, 108717. [Google Scholar] [CrossRef]
  9. Xu, N.; Lei, I.; Lin, Y.; Ju, L.S.; Morey, T.E.; Gravenstein, N.; Yang, J.; Martynyuk, A.E. A methyltransferase inhibitor (Decitabine) alleviates intergenerational effects of paternal neonatal exposure to anesthesia with sevoflurane. Anesth. Analg. 2020, 131, 1291–1299. [Google Scholar] [CrossRef]
  10. Adams, P.M.; Fabricant, J.D.; Legator, M.S. Active avoidance behavior in the F1 progeny of male rats exposed to cyclophosphamide prior to fertilization. Neurobehav. Toxicol. Teratol. 1982, 4, 531–534. [Google Scholar]
  11. Hsu, L.L.; Adams, P.M.; Legator, M.S. Cyclophosphamide- effects of paternal exposure on the brain chemistry of the F1 progeny. J. Toxicol. Environ. Health 1987, 21, 471–481. [Google Scholar] [CrossRef]
  12. Yang, F.; Chen, J.; Miao, M.H.; Yuan, W.; Li, L.; Liang, H.; Ehrenstein, V.; Li, J. Risk of autism spectrum disorder in offspring following paternal use of selective serotonin reuptake inhibitors before conception: A population-based cohort study. BMJ Open 2017, 7, e016368. [Google Scholar] [CrossRef]
  13. Yang, F.; Liang, H.; Chen, J.; Miao, M.; Yuan, W.; Norgaard, M.; Li, J. Prenatal paternal selective serotonin reuptake inhibitors use and risk of ADHD in offspring. Pediatrics 2018, 141, e20171081. [Google Scholar] [CrossRef]
  14. Tagne-Fotso, R.; Leroyer, A.; Howsam, M.; Dehon, B.; Richeval, C.; Nisse, C. Current sources of lead exposure and their relative contributions to the blood lead levels in the general adult population of northern France: The IMEPOGE Study, 2008–2010. J. Toxicol. Environ. Health 2016, 79, 245–265. [Google Scholar] [CrossRef]
  15. Nybo Andersen, A.M.; Urhoj, S.K. Is advanced paternal age a health risk for the offspring? Fertil. Steril. 2017, 107, 312–318. [Google Scholar] [CrossRef] [PubMed]
  16. Khandwala, Y.S.; Baker, V.L.; Shaw, G.M.; Stevenson, D.K.; Lu, Y.; Eisenberg, M.L. Association of paternal age with perinatal outcomes between 2007 and 2016 in the United States: Population based cohort study. BMJ Clin. Res. Ed. 2018, 363, k4372. [Google Scholar] [CrossRef] [PubMed]
  17. Chen, Q.; Yan, W.; Duan, E. Epigenetic inheritance of acquired traits through sperm RNAs and sperm RNA modifications. Nat. Rev. Genet. 2016, 17, 733–743. [Google Scholar] [CrossRef]
  18. Curley, J.P.; Mashoodh, R.; Champagne, F.A. Epigenetics and origins of paternal effects. Horm. Behav. 2011, 59, 306–314. [Google Scholar] [CrossRef]
  19. Hanson, M.A.; Skineer, M.K. Developmental origins of epigenetic transgenerational inheritance. Environ. Epigenetics 2016, 2, dvw002. [Google Scholar] [CrossRef]
  20. Poynor, D.H.; Lupkiewicz, S.; Lubs, H.A.; Williams, C.A. Paternal exposures and the question of birth defects. J. Fla. Med. Assoc. 1997, 84, 323–326. [Google Scholar]
  21. The European Parliament and the Council of the European Union. Directive (EU) 2022/431 of the European Parliament and of the Council of 9 March 2022 Amending Directive 2004/37/EC on the Protection of Workers from the Risks Related to Exposure to Carcinogens or Mutagens at Work; European Union: Brussels, Belgium, 2022. [Google Scholar]
  22. Tricco, A.C.; Lillie, E.; Zarin, W.; O’Brien, K.K.; Colquhoun, H.; Levac, D.; Moher, D.; Peters, M.D.; Horsley, T.; Weeks, L.; et al. PRISMA extension for scoping reviews (PRISMA-ScR): Checklist and explanation. Ann. Intern. Med. 2018, 169, 467–473. [Google Scholar] [CrossRef]
  23. Dobrzynska, M.M.; Tyrkiel, E.J.; Pachocki, K.A. Developmental toxicity in mice following paternal exposure to di-n-butyl-phthalate (DBP). Biomed. Environ. Sci. 2011, 24, 569–578. [Google Scholar]
  24. Reshma Anjum, M.; Sainath, S.B.; Suneetha, Y.; Sreenivasula Reddy, P. Lead acetate induced reproductive and paternal mediated developmental toxicity in rats. Ecotoxicol Environ. Saf. 2011, 74, 793–799. [Google Scholar] [CrossRef]
  25. Cordier, S. Evidence for a role of paternal exposures in developmental toxicity. Basic Clin. Pharmacol. Toxicol. 2008, 102, 176–181. [Google Scholar] [CrossRef]
  26. Anderson, D.; Schmid, T.E.; Baumgartner, A. Male-mediated developmental toxicity. Asian J. Androl. 2014, 16, 81–88. [Google Scholar] [CrossRef] [PubMed]
  27. Klemmt, L.; Scialli, A.R. The transport of chemicals in semen. Birth Defects Res. Part B Dev. Reprod. Toxicol. 2005, 74, 119–131. [Google Scholar] [CrossRef] [PubMed]
  28. Carignan, C.C.; Mínguez-Alarcón, L.; Williams, P.L.; Meeker, J.D.; Stapleton, H.M.; Butt, C.M.; Toth, T.L.; Ford, J.B.; Hauser, R. EARTH Study Team Paternal urinary concentrations of organophosphate flame retardant metabolites, fertility measures and pregnancy outcomes among couples undergoing in vitro fertilization. Environ. Int. 2018, 111, 232–238. [Google Scholar] [CrossRef] [PubMed]
  29. Beal, M.A.; Yauk, C.L.; Marchetti, F. From sperm to offspring: Assessing the heritable genetic consequences of paternal smoking and potential public health impacts. Mutat. Res. 2017, 773, 26–50. [Google Scholar] [CrossRef]
  30. Moore, L.D.; Le, T.; Fan, G. DNA methylation and its basic function. Neuropsychopharmacology 2013, 38, 23–38. [Google Scholar] [CrossRef]
  31. Nilsson, E.E.; Sadler-Riggleman, I.; Skinner, M.K. Environmentally induced epigenetic transgenerational inheritance of disease. Environ. Epigenetics 2018, 4, dvy016. [Google Scholar] [CrossRef]
  32. Erkek, S.; Hisano, M.; Liang, C.Y.; Gill, M.; Murr, R.; Dieker, J.; Schubeler, D.; van der Vlag, J.; Stadler, M.B.; Peters, A.H. Molecular determinants of nucleosome retention at CpG-rich sequences in mouse spermatozoa. Nat. Struct. Mol. Biol. 2013, 20, 868–875. [Google Scholar] [CrossRef]
  33. Hammond, S.S.; Nix, D.A.; Zhang, H.; Purwar, J.; Carrell, D.T.; Cairns, B.R. Distinctive chromatin in human sperm packages genes for embryo development. Nature 2009, 460, 473–478. [Google Scholar] [CrossRef] [PubMed]
  34. Ibi, D.; Fujiki, Y.; Koide, N.; Nakasai, G.; Takaba, R.; Hiramatsu, M. Paternal valproic acid exposure in mice triggers behavioral alterations in offspring. Neurotoxicol. Teratol. 2019, 76, 106837. [Google Scholar] [CrossRef] [PubMed]
  35. Yuan, S.; Schuster, A.; Tang, C.; Yu, T.; Ortogero, N.; Bao, J.; Zheng, H.; Yan, W. Sperm-borne miRNAs and endo-siRNA are important for fertilization and preimplantation embryonic development. Development 2016, 143, 635–647. [Google Scholar] [CrossRef] [PubMed]
  36. Krawetz, S.A.; Kruger, A.; Lalancette, C.; Tagett, R.; Anton, E.; Draghici, S.; Diamond, M.P. A survey of small RNAs in human sperm. Hum. Reprod. 2011, 26, 3401–3412. [Google Scholar] [CrossRef]
  37. Rassoulzadegan, M.; Grandjean, V.; Gounon, P.; Vincent, S.; Gillot, I.; Cuzin, F. RNA-mediated non-mendelian inheritance of an epigenetic change in the mouse. Nature 2006, 441, 469–474. [Google Scholar] [CrossRef]
  38. Champroux, A.; Cocquet, J.; Henry-Berger, J.; Drevet, J.R.; Kocer, A. A decade of exploring the mammalian sperm epigenome: Paternal epigenetic and transgenerational inheritance. Front. Cell Dev. Biol. 2018, 6, 50. [Google Scholar] [CrossRef]
  39. Donkin, I.; Barres, R. Sperm epigenetics and influence of environmental factors. Mol. Metab. 2018, 14, 1–11. [Google Scholar] [CrossRef]
  40. Lo, J.O.; Hedges, J.C.; Chou, W.H.; Tager, K.R.; Bachli, I.D.; Hagen, O.L.; Murphy, S.K.; Hanna, C.B.; Easley, C.A. Influence of substance use on male reproductive health and offspring outcomes. Nat. Rev. 2024, 21, 534–564. [Google Scholar] [CrossRef]
  41. Finelli, R.; Mottola, F.; Agarwal, A. Impact of alcohol consumption on male fertility potential: A narrative review. Int. J. Environ. Res. Public Health 2021, 19, 328. [Google Scholar] [CrossRef]
  42. Lo, J.O.; Hedges, J.C.; Girardi, G. Impact of cannabinoids on pregnancy, reproductive health, and offspring outcomes. Am. J. Obstet. Gynecol 2022, 227, 571–581. [Google Scholar] [CrossRef]
  43. Ryan, K.S.; Bash, J.C.; Hanna, C.B.; Hedges, J.C.; Lo, J.O. Effects of marijuana on reproductive health: Preconception and gestational effects. Curr. Opin. Endocrinol. Diabetes Obes. 2021, 28, 558–565. [Google Scholar] [CrossRef] [PubMed]
  44. Lo, J.O.; D’Mello, R.J.; Watch, L.; Schust, D.J.; Murphy, S.K. An epigenetic synopsis of parental substance use. Epigenomics 2023, 15, 453–473. [Google Scholar] [CrossRef] [PubMed]
  45. Easey, K.E.; Sharp, G.C. The impact of paternal alcohol, tobacco, caffeine use and physical activity on offspring mental health: A systematic review and meta-analysis. Reprod. Health 2021, 18, 214. [Google Scholar] [CrossRef] [PubMed]
  46. Lo, J.O.; Shaw, B.; Robalino, S.; Ayers, C.K.; Durbin, S.; Rushkin, M.C.; Olyaei, A.; Kansagara, D.; Harrod, C.S. Cannabis use in pregnancy and neonatal outcomes: A systematic review and meta-analysis. Cannabis Cannabinoid Res. 2024, 9, 470–485. [Google Scholar] [CrossRef]
  47. Ross, E.J.; Graham, D.L.; Money, K.M.; Stanwood, G.D. Developmental consequences of fetal exposure to drugs: What we know and what we still must learn. Neuropsychopharmacology 2015, 40, 61–87. [Google Scholar] [CrossRef]
  48. Killinger, C.E.; Robinson, S.; Stanwood, G.D. Subtle biobehavioral effects produced by paternal cocaine exposure. Synapse 2012, 66, 902–908. [Google Scholar] [CrossRef]
  49. Vassoler, F.M.; White, S.L.; Schmidt, H.D.; Sadri-Vakili, G.; Pierce, R.C. Epigenetic inheritance of a cocaine-resistance phenotype. Nat. Neurosci. 2013, 16, 42–47. [Google Scholar] [CrossRef]
  50. Rodgers, A.B.; Morgan, C.P.; Bronson, S.L.; Revello, S.; Bale, T.L. Paternal stress exposure alters sperm microRNA content and reprograms offspring HPA stress axis regulation. J. Neurosci. 2013, 33, 9003–9012. [Google Scholar] [CrossRef]
  51. Salonen, I.; Pakarinen, P.; Huhtaniemi, I. Effect of chronic ethanol diet on expression of gonadotropin genes in the male rat. J. Pharmacol. Exp. Ther. 1992, 260, 463–467. [Google Scholar] [CrossRef]
  52. Salonen, I.; Huhtaniemi, I. Effects of chronic ethanol diet on pituitary-testicular function of the rat. Biol. Reprod. 1990, 42, 55–62. [Google Scholar] [CrossRef]
  53. La Vignera, S.; Condorelli, R.A.; Balercia, G.; Vicari, E.; Calogero, A.E. Does alcohol have any effect on male reproductive function? A review of literature. Asian J. Androl. 2013, 15, 221–225. [Google Scholar] [CrossRef]
  54. 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]
  55. Adler, R.A. Clinical review 33: Clinically important effects of alcohol on endocrine function. J. Clin. Endocrinol. Metab. 1992, 74, 957–960. [Google Scholar]
  56. Emanuele, M.A.; Emanuele, N.V. Alcohol’s effects on male reproduction. Alcohol Health Res. World 1998, 22, 195–201. [Google Scholar]
  57. Grover, S.; Mattoo, S.K.; Pendharkar, S.; Kandappan, V. Sexual dysfunction in patients with alcohol and opioid dependence. Indian J. Psychol. Med. 2014, 36, 355–365. [Google Scholar] [CrossRef] [PubMed]
  58. Chang, R.C.; Wang, H.; Bedi, Y.; Golding, M.C. Preconception paternal alcohol exposure exerts sex-specific effects on offspring growth and long-term metabolic programming. Epigenetics Chromatin 2019, 12, 9. [Google Scholar] [CrossRef] [PubMed]
  59. Thomas, K.N.; Srikanth, N.; Bhadsavle, S.S.; Thomas, K.R.; Zimmel, K.N.; Basel, A.; Roach, A.N.; Mehta, N.A.; Bedi, Y.S.; Golding, M.C. Preconception paternal ethanol exposures induce alcohol-related craniofacial growth deficiencies in fetal offspring. J. Clin. Investig. 2023, 133, e167624. [Google Scholar] [CrossRef]
  60. Zhou, Q.; Song, L.; Chen, J.; Wang, Q.; Shen, H.; Zhang, S.; Li, X. Association of preconception paternal alcohol consumption with increased fetal birth defect risk. JAMA Pediatr. 2021, 175, 742–743. [Google Scholar] [CrossRef]
  61. Liang, F.; Diao, L.; Liu, J.; Jiang, N.; Zhang, J.; Wang, H.; Zhou, W.; Huang, G.; Ma, D. Paternal ethanol exposure and behavioral abnormities in offspring: Associated alterations in imprinted gene methylation. Neuropharmacology 2014, 81, 126–133. [Google Scholar] [CrossRef]
  62. Meek, L.R.; Myren, K.; Sturm, J.; Burau, D. Acute paternal alcohol use affects offspring development and adult behavior. Physiol. Behav. 2007, 91, 154–160. [Google Scholar] [CrossRef]
  63. Hayer, S.; Mandelbaum, A.D.; Watch, L.; Ryan, K.S.; Hedges, M.A.; Manuzak, J.A.; Easley, C.A.; Schust, D.J.; Lo, J.O. Cannabis and pregnancy: A review. Obs. Gynecol. Surv. 2023, 78, 411–428. [Google Scholar] [CrossRef]
  64. Lo, J.O.; Hedges, J.C.; Metz, T.D. Cannabis use and perinatal health research. JAMA 2023, 330, 913–914. [Google Scholar] [CrossRef]
  65. Rubinstein, A.L.; Carpenter, D.M. Association between commonly prescribed opioids and androgen deficiency in men: A retrospective cohort analysis. Pain Med. 2017, 18, 637–644. [Google Scholar] [CrossRef]
  66. Eshraghi, Y.; Hanks, N.; Rooney, S.; Yousefi Ata, F.M.; Velasco, C.; Guirguis, M.; Uwaifo, G. Establishing a dose-response relationship between opioid use and hypogonadism: A retrospective case-control study. Ochsner J. 2021, 21, 249–253. [Google Scholar] [CrossRef] [PubMed]
  67. Goldberg, L.R.; Gould, T.J. Multigenerational and transgenerational effects of paternal exposure to drugs of abuse on behavioral and neural function. Eur. J. Neurosci. 2019, 50, 2453–2466. [Google Scholar] [CrossRef] [PubMed]
  68. Jalali, Z.; Bahrampour, S.; Khalili, P.; Khademalhosseini, M.; Esmaeili Nadimi, A. Cohort based analysis of paternal opioid use in relation to offspring’s BMI and plasma lipid profile. Sci. Rep. 2021, 11, 9462. [Google Scholar] [CrossRef] [PubMed]
  69. Pachenari, N.; Azizi, H.; Ghasemi, E.; Azadi, M.; Semnanian, S. Exposure to opiates in male adolescent rats alters pain perception in the male offspring. Behav. Pharmacol. 2018, 29, 255–260. [Google Scholar] [CrossRef]
  70. Azadi, M.; Moazen, P.; Wiskerke, J.; Semnanian, S.; Azizi, H. Preconception paternal morphine exposure leads to an impulsive phenotype in male rat progeny. Psychopharmacology 2021, 238, 3435–3446. [Google Scholar] [CrossRef]
  71. Ellis, A.S.; Toussaint, A.B.; Knouse, M.C.; Thomas, A.S.; Bongiovanni, A.R.; Mayberry, H.L.; Bhakta, S.; Peer, K.; Bangasser, D.A.; Wimmer, M.E. Paternal morphine self-administration produces object recognition memory deficits in female, but not male offspring. Psychopharmacology 2020, 237, 1209–1221. [Google Scholar] [CrossRef]
  72. Mitra, A.; Chakraborty, B.; Mukhopadhay, D.; Pal, M.; Mukherjee, S.; Banerjee, S.; Chaudhuriet, K. Effect of smoking on semen quality, FSH, testosterone level, and CAG repeat length in androgen receptor gene of infertile men in an Indian city. Syst. Biol. Reprod. Med. 2012, 58, 255–262. [Google Scholar] [CrossRef]
  73. Tweed, J.O.; Hsia, S.H.; Lutfy, K.; Friedman, T.C. The endocrine effects of nicotine and cigarette smoke. Trends Endocrinol. Metab. 2012, 23, 334–342. [Google Scholar] [CrossRef] [PubMed]
  74. Du Fossé, N.A.; Petronella van der Hoorn, M.L.; Buisman, N.H.; vaqn Lith, I.N.N.; le Cessie, S.; Lashley, L.E.E.L.O. Paternal smoking is associated with an increased risk of pregnancy loss in a dose-dependent manner: A systematic review and meta-analysis. FS Rev. 2021, 2, 227–238. [Google Scholar] [CrossRef]
  75. Zhou, Q.; Zhang, S.; Wang, Q.; Shen, H.; Zhang, Y.; Tian, W.; Li, X. Association between preconception paternal smoking and birth defects in offspring: Evidence from the database of the National Free Preconception Health Examination Project in China. BJOG 2020, 127, 1358–1364. [Google Scholar] [CrossRef] [PubMed]
  76. Sawyer, D.E.; Aitke, R.J. Male-mediated developmental defects and childhood disease. Reprod. Med. Rev. 2000, 8, 107–126. [Google Scholar] [CrossRef]
  77. Baldacci, S.; Gorini, F.; Santoro, M.; Pierini, A.; Minichilli, F.; Bianchi, F. Environmental and individual exposure and the risk of congenital anomalies: A review of recent epidemiological evidence. Epidemiol. Prev. 2018, 42 (Suppl. S1), 1–34. [Google Scholar]
  78. Savits, D.A.; Sonnefeld, N.L.; Olshan, A.F. Review of epidemiologic studies of paternal occupational exposure and spontaneous abortion. Am. J. Ind. Med. 1994, 25, 361–383. [Google Scholar] [CrossRef]
  79. Logman, J.F.S.; de Vries, L.E.; Hemels, M.E.H.; Khattak, S.; Einarson, T.R. Paternal organic solvent exposure and adverse pregnancy outcomes: A meta-analysis. Am. J. Ind. Med. 2005, 47, 37–44. [Google Scholar] [CrossRef]
  80. Hooiveld, M.; Haveman, W.; Roskes, K.; Bretveld, R.; Burstyn, I.; Roeleveld, N. Adverse reproduction outcomes among male painters with occupational exposure to organic solvents. Occup. Environ. Med. 2006, 63, 538–544. [Google Scholar] [CrossRef]
  81. Nieuwenhuijsen, M.J.; Dadvand, P.; Grellier, J.; Martinez, D.; Vrijheid, M. Environmental risk factors of pregnancy outcomes: A summary of recent meta-analysis of epidemiological studies. Environ. Health 2013, 12, 6. [Google Scholar] [CrossRef]
  82. Jørgensen, K.T.; Jensen, M.S.; Toft, G.V.; Larsen, A.D.; Bonde, J.P.; Hougaard, K.S. Risk of cryptorchidism among sons of horticultural workers and farmers in Denmark. Scand. J. Work Environ. Health 2014, 40, 323–330. [Google Scholar] [CrossRef]
  83. Snijder, C.A.; Vlot, I.J.; Burdorf, A.; Obermann-Borst, S.A.; Helbing, W.A.; Wildhagen, M.F.; Steegers, E.A.P.; Steegers-Theunissen, R.P.M. Congenital heart defects and parental occupational exposure to chemicals. Hum. Reprod. 2012, 27, 1510–1517. [Google Scholar] [CrossRef] [PubMed]
  84. Dimich-Ward, H.; Hertzman, C.; Teschke, K.; Hershler, R.; Marion, S.A.; Ostry, A.; Kelly, S. Reproductive effects of paternal exposure to chlorophenate wood preservatives in the sawmill industry. Scand. J. Work. Environ. Health 1996, 22, 267–273. [Google Scholar] [CrossRef]
  85. Mirilas, P.; Mentessidou, A.; Kontis, E.; Asimakidou, M.; Moxham, B.J.; Petropoulos, A.S.; Emmanouil-Nikolousi, E.N. Parental exposures and risk of nonsyndromic orofacial clefts in offspring: A case-control study in Greece. Int. J. Pediatr. Otorhinolaryngol. 2011, 75, 695–699. [Google Scholar] [CrossRef]
  86. PLoS Medicine Editors. Best practice in systematic reviews: The importance of protocols and registration. PLoS Med. 2011, 8, e1001009. [Google Scholar]
Toxics 13 00707 g001
Figure 1. Selection process for scientific papers.
Figure 1. Selection process for scientific papers.
Toxics 13 00707 g001
Table 1. Effects of substances of abuse on male reproductive health and offspring.
Table 1. Effects of substances of abuse on male reproductive health and offspring.
Type of Substance UseTarget of ReprotoxicityIn DetailEffects on Offspring
AlcoholAlters male reproductive hormones [41,51,52]
Alters semen parameters [42,53,54]
Testicular volume [55,56]
Erectile and sexual function [57]		Higher: LH 1, FSH 2, DNA 3 fragmentation; lower: testosterone, seminal volume and sperm count, motility and morphologyIncreased intrauterine growth restriction
Increased birth defects, decreased birthweight
Increased risk of cancers (leukemia and brain tumors)
[41,58,59,60,61,62]
Cannabis (in particular THC 4)Alters male reproductive hormones, semen parameters, libido, erectile and sexual function [42,43]Lower: LH and sperm count, motility and morphology; higher: sperm DNA fragmentation. Testosterone levels were found to be both higher than lowerIncreased pregnancy loss, increased congenital cardiac anomalies
Increased behavioral issues
[43,63,64]
OpioidsChronic opioid use was linked with an increased risk of androgen suppression [65,66]Lower: GRH 5 secretion, testosterone, sperm motility and morphology; higher sperm DNA fragmentationDecreased fetal weight
Increased withdrawal-like behaviors
Increased risk of opioid addiction, delayed learning, and impulsive behaviors
[67,68,69,70,71]
Tobacco smoke (nicotine in particular)Alters sexual hormones, testis, and sperm [72,73]Higher: testosterone levels; lower: sperm count, motility and morphology. Both higher and lower LH and/or FSHIncreased pregnancy loss
Increased testosterone levels in child < 1 years
Decreased sperm count and increased risk of neurodivergent behavior in childhood and adolescent
[74,75]
1 LH—Luteinizing hormone; 2 FSH—Follicle-Stimulating Hormone; 3 DNA—deoxyribonucleic acid; 4 THC—∆9-Tetrahydrocannabinol; 5 GRH—Growth hormone-releasing hormone.
Table 2. Occupational exposure to chemicals of male workers and effects for offsprings.
Table 2. Occupational exposure to chemicals of male workers and effects for offsprings.
Ref.ChemicalsEffects for OffspringResults
[81]SolventsNeural tube defectsOR 1 = 1.86, 95% CI 2 1.40–2.46
SolventsAnencephalyOR = 2.18, 95% CI 1.52–3.11
SolventsSpina bifidaOR = 1.59, 95% CI 0.99–2.56
PesticidesHypospadiasRR = 1.19, 95% CI 1.00–1.41
[82]PesticidesCryptorchidismOR = 1.04, 95% CI 0.96–1.12
[83]Phthalates and polychlorinated compoundsCongenital heart defectsOR = 2.08, 95% CI 1.27–3.40
PhthalatesPerimembranous ventricular septal defectOR = 2.84, 95% CI 1.37–5.92
BisphenolsAtrial ventricular septal defectsOR = 4.22, 95% CI 1.23–14.42
AlkylphenolsCoarctation of aortaOR = 3.85, 95% CI 1.17–12.67
[84]Chlorophenate wood preservativesEye malformationsOR = 2.87, 95% CI 1.5–5.5
CataractsOR = 5.68, 95% CI 1.4–22.6
Undescended testiclesOR = 1.16, 95% CI 0.8–1.6
Genital organs in generalOR = 1.29 95% CI 0.9–1.5
Spina bifidaOR = 1.32 95% CI 0.2–2.1
[85]PesticidesCleft lipOR = 3.00 95% CI 1.03–8.70
[79]Solvents in painting activityBirth defectsOR = 1.86 95% CI 1.4–2.5
[80]Solvents in painting activityBirth defectsOR = 6.2 95% CI 1.4–28
1 OR—Odds ratio; 2 CI—confidence interval.
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Caporossi, L.; Castellano, P.; Paci, E.; Pigini, D. A Scoping Review on Male-Mediated Developmental Toxicity. Toxics 2025, 13, 707. https://doi.org/10.3390/toxics13090707

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Caporossi L, Castellano P, Paci E, Pigini D. A Scoping Review on Male-Mediated Developmental Toxicity. Toxics. 2025; 13(9):707. https://doi.org/10.3390/toxics13090707

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Caporossi, Lidia, Paola Castellano, Enrico Paci, and Daniela Pigini. 2025. "A Scoping Review on Male-Mediated Developmental Toxicity" Toxics 13, no. 9: 707. https://doi.org/10.3390/toxics13090707

APA Style

Caporossi, L., Castellano, P., Paci, E., & Pigini, D. (2025). A Scoping Review on Male-Mediated Developmental Toxicity. Toxics, 13(9), 707. https://doi.org/10.3390/toxics13090707

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