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Search Results (175)

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Keywords = male reproduction dysfunction

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28 pages, 3469 KiB  
Review
Prostate Cancer Treatments and Their Effects on Male Fertility: Mechanisms and Mitigation Strategies
by Aris Kaltsas, Nikolaos Razos, Zisis Kratiras, Dimitrios Deligiannis, Marios Stavropoulos, Konstantinos Adamos, Athanasios Zachariou, Fotios Dimitriadis, Nikolaos Sofikitis and Michael Chrisofos
J. Pers. Med. 2025, 15(8), 360; https://doi.org/10.3390/jpm15080360 - 7 Aug 2025
Abstract
Prostate cancer (PCa) is the second most frequently diagnosed malignancy in men worldwide. Although traditionally considered a disease of older men, the incidence of early-onset PCa (diagnosis < 55 years) is steadily rising. Advances in screening and therapy have significantly improved survival, creating [...] Read more.
Prostate cancer (PCa) is the second most frequently diagnosed malignancy in men worldwide. Although traditionally considered a disease of older men, the incidence of early-onset PCa (diagnosis < 55 years) is steadily rising. Advances in screening and therapy have significantly improved survival, creating a growing cohort of younger survivors for whom post-treatment quality of life—notably reproductive function—is paramount. Curative treatments such as radical prostatectomy, pelvic radiotherapy, androgen-deprivation therapy (ADT), and chemotherapy often cause irreversible infertility via multiple mechanisms, including surgical disruption of the ejaculatory tract, endocrine suppression of spermatogenesis, direct gonadotoxic injury to the testes, and oxidative sperm DNA damage. Despite these risks, fertility preservation is frequently overlooked in pre-treatment counseling, leaving many patients unaware of their options. This narrative review synthesizes current evidence on how PCa therapies impact male fertility, elucidates the molecular and physiological mechanisms of iatrogenic infertility, and evaluates both established and emerging strategies for fertility preservation and restoration. Key interventions covered include sperm cryopreservation, microsurgical testicular sperm extraction (TESE), and assisted reproductive technologies (ART). Psychosocial factors influencing decision-making, novel biomarkers predictive of post-treatment spermatogenic recovery, and long-term offspring outcomes are also examined. The review underscores the urgent need for timely, multidisciplinary fertility consultation as a routine component of PCa care. As PCa increasingly affects men in their reproductive years, proactively integrating preservation into standard oncologic practice should become a standard survivorship priority. Full article
(This article belongs to the Special Issue Clinical Advances in Male Genitourinary and Sexual Health)
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22 pages, 884 KiB  
Article
Mitochondrial Dysregulation in Male Infertility: A Preliminary Study for Infertility-Specific lncRNA Variants
by Georgios Stamatellos, Maria-Anna Kyrgiafini, Aris Kaltsas and Zissis Mamuris
DNA 2025, 5(3), 38; https://doi.org/10.3390/dna5030038 - 5 Aug 2025
Viewed by 41
Abstract
Background/Objectives: Male infertility is a major health concern with a complex etiopathology, yet a substantial proportion of cases remain idiopathic. Mitochondrial dysfunction and non-coding RNA (ncRNA) deregulation have both been implicated in impaired spermatogenesis, but their interplay remains poorly understood. This study aimed [...] Read more.
Background/Objectives: Male infertility is a major health concern with a complex etiopathology, yet a substantial proportion of cases remain idiopathic. Mitochondrial dysfunction and non-coding RNA (ncRNA) deregulation have both been implicated in impaired spermatogenesis, but their interplay remains poorly understood. This study aimed to identify infertility-specific variants in ncRNAs that affect mitochondrial dynamics and homeostasis and to explore their roles. Methods: Whole-genome sequencing (WGS) was performed on genomic DNA samples from teratozoospermic, asthenozoospermic, oligozoospermic, and normozoospermic men. Variants uniquely present in infertile individuals and mapped to ncRNAs that affect mitochondrial dynamics were selected and prioritized using bioinformatics tools. An independent transcriptomic validation was conducted using RNA-sequencing data from testicular biopsies of men with non-obstructive azoospermia (NOA) to determine whether the ncRNAs harboring WGS-derived variants were transcriptionally altered. Results: We identified several infertility-specific variants located in lncRNAs known to interact with mitochondrial regulators, including GAS5, HOTAIR, PVT1, MEG3, and CDKN2B-AS1. Transcriptomic analysis confirmed significant deregulation of these lncRNAs in azoospermic testicular samples. Bioinformatic analysis also implicated the disruption of lncRNA–miRNA–mitochondria networks, potentially contributing to mitochondrial membrane potential loss, elevated reactive oxygen species (ROS) production, impaired mitophagy, and germ cell apoptosis. Conclusions: Our integrative genomic and transcriptomic analysis highlights lncRNA–mitochondrial gene interactions as a novel regulatory layer in male infertility, while the identified lncRNAs hold promise as biomarkers and therapeutic targets. However, future functional studies are warranted to elucidate their mechanistic roles and potential for clinical translation in reproductive medicine. Full article
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18 pages, 1102 KiB  
Review
Exploring Human Sperm Metabolism and Male Infertility: A Systematic Review of Genomics, Proteomics, Metabolomics, and Imaging Techniques
by Achraf Zakaria, Idrissa Diawara, Amal Bouziyane and Noureddine Louanjli
Int. J. Mol. Sci. 2025, 26(15), 7544; https://doi.org/10.3390/ijms26157544 - 5 Aug 2025
Viewed by 161
Abstract
Male infertility is a multifactorial condition often associated with disruptions in sperm metabolism and mitochondrial function, yet traditional semen analysis provides limited insight into these molecular mechanisms. Understanding sperm bioenergetics and metabolic dysfunctions is crucial for improving the diagnosis and treatment of conditions [...] Read more.
Male infertility is a multifactorial condition often associated with disruptions in sperm metabolism and mitochondrial function, yet traditional semen analysis provides limited insight into these molecular mechanisms. Understanding sperm bioenergetics and metabolic dysfunctions is crucial for improving the diagnosis and treatment of conditions such as asthenozoospermia and azoospermia. This systematic review synthesizes recent literature, focusing on advanced tools and techniques—including omics technologies, advanced imaging, spectroscopy, and functional assays—that enable comprehensive molecular assessment of sperm metabolism and development. The reviewed studies highlight the effectiveness of metabolomics, proteomics, and transcriptomics in identifying metabolic biomarkers linked to male infertility. Non-invasive imaging modalities such as Raman and magnetic resonance spectroscopy offer real-time metabolic profiling, while the seminal microbiome is increasingly recognized for its role in modulating sperm metabolic health. Despite these advances, challenges remain in clinical validation and implementation of these techniques in routine infertility diagnostics. Integrating molecular metabolic assessments with conventional semen analysis promises enhanced diagnostic precision and personalized therapeutic approaches, ultimately improving reproductive outcomes. Continued research is needed to standardize biomarkers and validate clinical utility. Furthermore, these metabolic tools hold significant potential to elucidate the underlying causes of previously misunderstood and unexplained infertility cases, offering new avenues for diagnosis and treatment. Full article
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18 pages, 2393 KiB  
Review
Aggressive Mating Behavior in Roosters (Gallus gallus domesticus): A Narrative Review of Behavioral Patterns
by Mihnea Lupu, Dana Tăpăloagă, Elena Mitrănescu, Raluca Ioana Rizac, George Laurențiu Nicolae and Manuella Militaru
Life 2025, 15(8), 1232; https://doi.org/10.3390/life15081232 - 3 Aug 2025
Viewed by 219
Abstract
This review explores sexual aggression in broiler breeder males, aiming to synthesize existing scientific evidence regarding its causes, behavioral manifestations, and consequences, while addressing the genetic, neuroendocrine, and environmental mechanisms involved. Through an extensive analysis of scientific literature, the paper highlights that intensive [...] Read more.
This review explores sexual aggression in broiler breeder males, aiming to synthesize existing scientific evidence regarding its causes, behavioral manifestations, and consequences, while addressing the genetic, neuroendocrine, and environmental mechanisms involved. Through an extensive analysis of scientific literature, the paper highlights that intensive genetic selection aimed at enhancing growth and productivity has resulted in unintended behavioral dysfunctions. These include the reduction or absence of courtship behavior, the occurrence of forced copulations, and a notable increase in injury rates among hens. Reproductive challenges observed in meat-type breeder flocks, in contrast to those in layer lines, appear to stem from selection practices that have overlooked traits related to mating behavior. Environmental and managerial conditions, including photoperiod manipulation, stocking density, nutritional imbalances, and the use of mixed-sex rearing systems, are also identified as contributing factors to the expression of sexual aggression. Furthermore, recent genetic findings indicate a potential link between inherited neurobehavioral factors and aggressive behavior, with the SORCS2 gene emerging as a relevant candidate. Based on these insights, the review emphasizes the importance of considering behavioral parameters in breeding programs in order to reconcile productivity objectives with animal welfare standards. Future research may benefit from a more integrative approach that combines behavioral, physiological, and genomic data to better understand and address the multifactorial nature of sexual aggression in poultry systems. Full article
(This article belongs to the Section Animal Science)
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21 pages, 1962 KiB  
Review
From Survival to Parenthood: The Fertility Journey After Childhood Cancer
by Sofia Rahman, Veronica Sesenna, Diana Osorio Arce, Erika Maugeri and Susanna Esposito
Biomedicines 2025, 13(8), 1859; https://doi.org/10.3390/biomedicines13081859 - 30 Jul 2025
Viewed by 219
Abstract
Background: The advances in cancer diagnosis and treatment have significantly improved survival rates in pediatric patients, with five-year survival now exceeding 80% in many high-income countries. However, these life-saving therapies often carry long-term consequences, including impaired fertility. The reproductive health of childhood [...] Read more.
Background: The advances in cancer diagnosis and treatment have significantly improved survival rates in pediatric patients, with five-year survival now exceeding 80% in many high-income countries. However, these life-saving therapies often carry long-term consequences, including impaired fertility. The reproductive health of childhood cancer survivors has emerged as a key issue in survivorship care. Objective: This narrative review aims to examine the gonadotoxic effects of cancer treatments on pediatric patients, evaluate fertility preservation strategies in both males and females, and provide guidance on the long-term monitoring of reproductive function post treatment. Methods: A comprehensive literature review was conducted using PubMed, including randomized trials, cohort studies, and clinical guidelines published up to March 2024. The keywords focused on pediatric oncology, fertility, and reproductive endocrinology. Studies were selected based on relevance to treatment-related gonadotoxicity, fertility preservation options, and follow-up care. Results: Radiotherapy and alkylating agents pose the highest risk to fertility. Postpubertal patients have access to standardized preservation techniques, while prepubertal options remain experimental. Long-term effects include premature ovarian insufficiency, azoospermia, hypogonadism, and uterine dysfunction. The psychosocial impacts, especially in female survivors, are profound and often overlooked. Conclusions: Fertility preservation should be discussed at diagnosis and integrated into treatment planning in pediatric patients with cancer. While options for postpubertal patients are established, more research is needed to validate safe and effective strategies for younger populations. A multidisciplinary approach and long-term surveillance are essential for safeguarding future reproductive potential in childhood cancer survivors. Full article
(This article belongs to the Special Issue Advanced Cancer Diagnosis and Treatment: Third Edition)
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31 pages, 865 KiB  
Review
Beneficial Effects of Resveratrol on Testicular Functions: Focus on Its Antioxidant Properties
by Adele Chimento, Arianna De Luca, Massimo Venditti, Francesca De Amicis and Vincenzo Pezzi
Cells 2025, 14(14), 1122; https://doi.org/10.3390/cells14141122 - 21 Jul 2025
Viewed by 550
Abstract
Male infertility is a pathological condition that affects many subjects and for which a progressive increase in cases has been observed in recent years. The mechanisms underlying male reproductive system dysfunction are not fully understood and the specific drugs use has not produced [...] Read more.
Male infertility is a pathological condition that affects many subjects and for which a progressive increase in cases has been observed in recent years. The mechanisms underlying male reproductive system dysfunction are not fully understood and the specific drugs use has not produced optimal results. Therefore, the focus on developing new therapeutic options to prevent or treat this dysfunction is continuously growing. Defective sperm function has been associated with oxidative stress (OS) due to reactive oxygen species (ROS) excessive production. OS is related to mitochondrial dysfunction, lipid peroxidation, DNA damage and fragmentation, and ultimately sperm cell death. Many defense mechanisms to protect from ROS injuries have been developed; natural antioxidants, such as vitamin C and E are able to interact with oxidizing radicals, neutralizing them. Interestingly, resveratrol (RSV), a natural polyphenol with proven health-promoting actions, has been found to be an effective free radical scavenger in several in vitro and in vivo models, providing protection against OS. In this review, we discussed mechanisms related to the modulation of redox homeostasis in the testis and how the alteration of these processes can determine a damage in testicular function; particularly, we focused on the antioxidant properties of RSV that could give beneficial effects in preserving male fertility. Full article
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15 pages, 1920 KiB  
Article
The Absence of Bovine Serum Albumin (BSA) in Preimplantation Culture Media Impairs Embryonic Development and Induces Metabolic Alterations in Mouse Offspring
by Jannatul Ferdous Jharna, Md Wasim Bari, Norermi Firzana Alfian and Satoshi Kishigami
Int. J. Mol. Sci. 2025, 26(14), 6989; https://doi.org/10.3390/ijms26146989 - 21 Jul 2025
Viewed by 910
Abstract
Bovine serum albumin (BSA), the most commonly used protein in preimplantation embryo culture media, performs a variety of physiological functions. However, its involvement in long-term effects remains largely unclear. To investigate its physiological importance in culture media, we examined the developmental and metabolic [...] Read more.
Bovine serum albumin (BSA), the most commonly used protein in preimplantation embryo culture media, performs a variety of physiological functions. However, its involvement in long-term effects remains largely unclear. To investigate its physiological importance in culture media, we examined the developmental and metabolic consequences of BSA deprivation during preimplantation stages in mice. Embryos cultured in BSA-free media during specific time windows exhibited impaired blastocyst formation, with continuous deprivation from the two-pronuclei (2PN) stage significantly reducing trophectoderm (TE) and inner cell mass (ICM) cell numbers (p < 0.05), indicating compromised viability. Short-term BSA deprivation similarly disrupted lineage allocation, underscoring the sensitivity of early embryos to nutrient availability during cell fate determination. Although birth rates remained unaffected, suggesting compensatory mechanisms, longitudinal analysis revealed sex-specific metabolic dysfunction. Male offspring developed progressive glucose intolerance by 16 weeks, exhibiting elevated fasting glucose levels (p < 0.05) and impaired glucose clearance, whereas females showed no significant alterations in glucose metabolism. This study demonstrates that protein restriction during the preimplantation period not only disrupts early embryonic development but also programs long-term metabolic dysfunction, underscoring the importance of optimizing culture conditions in assisted reproductive technologies to minimize future health risks. Full article
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19 pages, 1944 KiB  
Article
Impact of Polystyrene Microplastics on Human Sperm Functionality: An In Vitro Study of Cytotoxicity, Genotoxicity and Fertility-Related Genes Expression
by Filomena Mottola, Maria Carannante, Ilaria Palmieri, Lorenzo Ibello, Luigi Montano, Mariaceleste Pezzullo, Nicola Mosca, Nicoletta Potenza and Lucia Rocco
Toxics 2025, 13(7), 605; https://doi.org/10.3390/toxics13070605 - 19 Jul 2025
Viewed by 521
Abstract
Polystyrene microplastics (PS-MPs) released in the environment reportedly affect the reproduction of various organisms, induced oxidative stress and apoptosis, resulting in altered sperm parameters. In this in vitro study, we tested the cytotoxicity and genotoxicity of PS-MPs by exposing human semen samples to [...] Read more.
Polystyrene microplastics (PS-MPs) released in the environment reportedly affect the reproduction of various organisms, induced oxidative stress and apoptosis, resulting in altered sperm parameters. In this in vitro study, we tested the cytotoxicity and genotoxicity of PS-MPs by exposing human semen samples to PS-MPs levels (105 and 210 μg/mL) for 30–60–90 min. Semen parameters, genome stability, sperm DNA fragmentation (SDF) and reactive oxygen species (ROS) production were analyzed before and after exposure. Moreover, we also evaluated the expression level of spermatozoa-specific expressed genes essential for the fusion with oocyte (DCST1, DCST2, IZUMO1, SPACA6, SOF1, and TMEM95). After PS-MP exposure, semen concentration and morphology did not differ, while sperm vitality and motility decreased in a time-dependent manner. In addition, sperm agglutination was observed in the groups exposed to both PS-MPs concentrations tested. A time- and concentration-dependent reduction in genomic stability, as well as increased SDF and ROS production, was also observed. Moreover, all investigated transcripts were down-regulated after PS-MP exposure. Our results confirm the oxidative stress-mediated genotoxicity and cytotoxicity of PS-MPs on human spermatozoa. The sperm agglutination observed after treatment could be due to the aggregation of PS-MPs already adhered to the sperm membranes, hindering sperm movement and fertilizing capability. Interestingly, the downregulation of genes required for sperm–oocyte fusion, resulting from data on the in vitro experimental system, suggests that PS-MP exposure may have implications for sperm functionality. While these findings highlight potential mechanisms of sperm dysfunction, further investigations using in vivo models are needed to determine their broader biological implications. Possible environmental and working exposure to pollutants should be considered during the counselling for male infertility. Full article
(This article belongs to the Section Reproductive and Developmental Toxicity)
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7 pages, 464 KiB  
Case Report
Biallelic Variants in DNAH12 Gene Linked to Male Infertility: Two New Cases and Literature Review
by Faisal H. Aljahdali, Rozana Kamal, Zohor Azher, Ahmed S. Zugail, Abdulaziz Baazeem, Aboulfazl Rad and Gabriela Oprea
Uro 2025, 5(3), 13; https://doi.org/10.3390/uro5030013 - 17 Jul 2025
Viewed by 210
Abstract
Background/Objectives: Although biallelic pathogenic variants in different DNAH gene family members have been associated with infertility, the role of DNAH12 in this disorder is still incompletely understood. To date, few patients have been shown to have infertility due to biallelic variants in this [...] Read more.
Background/Objectives: Although biallelic pathogenic variants in different DNAH gene family members have been associated with infertility, the role of DNAH12 in this disorder is still incompletely understood. To date, few patients have been shown to have infertility due to biallelic variants in this gene. Here, we report two more unrelated patients with infertility who carry homozygous variants in DNAH12. Methods: This study included two male patients with primary infertility and oligoasthenoteratozoospermia (OAT). Patient 1 was a 32-year-old with 1.5 years of infertility and no chronic illnesses or prior assisted reproductive technologies (ARTs). Patient 2 was a 49-year-old with 24 years of infertility, a history of varicocelectomy, and the occasional use of PRN analgesics for bone pain. Using genome sequencing, we identified two homozygous variants: c.3757C>A, p. Pro1253Thr, and c.11086-1G>A, p.?, in patients 1 and 2, respectively. Results: Our findings add supportive evidence that DNAH12 is a gene implicated in rare cases of male infertility. The identification of these homozygous variants in two additional patients supports the association between DNAH12 variants and reproductive dysfunction. Conclusions: This study highlights the need for further research on the role of DNAH12, including functional studies to clarify the mechanisms contributing to infertility. Full article
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19 pages, 1523 KiB  
Article
Multi- and Transgenerational Histological and Transcriptomic Outcomes of Developmental TCDD Exposure in Zebrafish (Danio rerio) Ovary
by Amelia Paquette, Emma Cavaneau, Alex Haimbaugh, Danielle N. Meyer, Camille Akemann, Nicole Dennis and Tracie R. Baker
Int. J. Mol. Sci. 2025, 26(14), 6839; https://doi.org/10.3390/ijms26146839 - 16 Jul 2025
Viewed by 390
Abstract
2,3,7,8-Tetrachlorodibenzo-p-dioxin (TCDD) exposure has long been associated with reproductive dysfunction in males and females even at miniscule levels, which can persist across generations. Given the continued industrial use and detection of other aryl hydrocarbon receptor (AhR) agonists in the general population [...] Read more.
2,3,7,8-Tetrachlorodibenzo-p-dioxin (TCDD) exposure has long been associated with reproductive dysfunction in males and females even at miniscule levels, which can persist across generations. Given the continued industrial use and detection of other aryl hydrocarbon receptor (AhR) agonists in the general population and the demonstrated heritable phenotypes of TCDD exposure, further work is justified to elucidate reproductive pathologies and minimize exposure risk. In females, multi- and transgenerational subfertility has been demonstrated in a zebrafish (Danio rerio) model exposed to 50 pg/mL TCDD once at 3 and 7 weeks post fertilization (wpf). We further characterize the histopathologic, hormonal and transcriptomic outcomes of the mature female zebrafish ovary following early-life TCDD exposure. Exposure was associated with significantly increased ovarian atresia in the F0 and F1, but not F2 generation. Other oocyte staging and vitellogenesis were unaffected in all generations. Exposed F0 females showed increased levels of whole-body triiodothyronine (T3) and 17β-estradiol (E2) levels, but not vitellogenin (Vtg), 11-ketotestosterone (11-KT), cortisol, thyroxine (T4), or testosterone (T). Ovarian transcriptomics were most dysregulated in the F2. Both F0 and F2, but not F1, showed changes in epigenetic-related gene expression. Rho signaling was the top pathway for both F0 and F2. Full article
(This article belongs to the Special Issue Molecular Research of Reproductive Toxicity)
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31 pages, 2326 KiB  
Review
“My Bitch Is Empty!” an Overview of the Preconceptional Causes of Infertility in Dogs
by Juliette Roos-Pichenot and Maja Zakošek Pipan
Vet. Sci. 2025, 12(7), 663; https://doi.org/10.3390/vetsci12070663 - 12 Jul 2025
Viewed by 1100
Abstract
Infertility is a complex and common problem in reproductive medicine consultations. Three factors must be examined during the preconception phase: breeding management, the fertility of the bitch, and the fertility of the stud dog. Among these factors, improper breeding management remains the main [...] Read more.
Infertility is a complex and common problem in reproductive medicine consultations. Three factors must be examined during the preconception phase: breeding management, the fertility of the bitch, and the fertility of the stud dog. Among these factors, improper breeding management remains the main cause of reproductive failure, with accurate recognition of ovulation being crucial for successful mating. Artificial insemination allows for a thorough evaluation of semen quality compared to natural mating. In addition, genetic selection, nutritional factors, and reproductive health management can either impair or improve the fertility of females and males. Idiopathic infertility can occur in bitches, but it is important to rule out other possible causes first. In bitches with irregular estrus cycles, ovarian dysfunction and endocrine imbalances should be investigated. In bitches with regular cycles, uterine disorders such as cystic endometrial hyperplasia, endometritis or congenital anomalies may be the cause. Both mating-related and chronic endometritis are recognized as contributing factors to infertility. Infectious agents, particularly Brucella spp. and Mycoplasma spp., should also be evaluated, although interpretation of Mycoplasma test results requires caution. In males presenting with poor semen quality, potential causes include infectious diseases (with brucellosis always requiring exclusion), hormonal imbalances, and the impact of exogenous treatments. The article underscores the critical role of comprehensive diagnostic protocols, proactive health surveillance, and data-driven breeding strategies in systematically addressing this multifaceted challenge. Full article
(This article belongs to the Section Veterinary Reproduction and Obstetrics)
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22 pages, 4716 KiB  
Article
Therapeutic Benefits of Nano-Echinacea Extract on Reproductive Injury Induced by Polystyrene Plastic Materials in Rat Model via Regulating Gut–Brain Axis
by Yi-Yuh Hwang, Sabri Sudirman, Pei-Xuan Tsai, Chine-Feng Mao, Athira Johnson, Tai-Yuan Chen, Deng-Fwu Hwang and Zwe-Ling Kong
Int. J. Mol. Sci. 2025, 26(13), 6097; https://doi.org/10.3390/ijms26136097 - 25 Jun 2025
Viewed by 499
Abstract
Plastics pollution is a critical global environmental issue, with growing concern over the increasing presence of nanoplastic particles. Plastics are major environmental pollutants that adversely affect human health, particularly when plastics from food sources enter the body and pose potential risks to reproductive [...] Read more.
Plastics pollution is a critical global environmental issue, with growing concern over the increasing presence of nanoplastic particles. Plastics are major environmental pollutants that adversely affect human health, particularly when plastics from food sources enter the body and pose potential risks to reproductive health. Echinacea purpurea is an immunologically active medicinal plant containing phenolic acids and alkylamides. Nanoparticles present a promising approach to enhance the effectiveness, stability, and bioavailability of Echinacea purpurea ethanol extract (EE) active components. This study aimed to determine the protective effects of chitosan-silica-Echinacea purpurea nanoparticles (CSE) against reproductive injury induced by polystyrene nanoplastics (PS-NPs) in male rats. The results showed that CSE dose-dependently reduced oxidative damage and protected intestinal and reproductive health. Furthermore, CSE improved gut microbiota dysbiosis, preserved barrier integrity, and attenuated PS-NPs-induced inflammation in the colon, brain, and gonads. Inflammatory factors released from the gut can enter the bloodstream, cross the blood–brain barrier, and potentially modulate the hypothalamic–pituitary–gonadal (HPG) axis. CSE has also been shown to elevate neurotransmitter levels in the colon and brain, thereby repairing HPG axis dysregulation caused by PS-NPs through gut–brain communication and improving reproductive dysfunction. This study enhances our understanding of CSE in modulating the gut–brain and HPG axes under PS-NPs-induced damage. CSE demonstrates the capacity to provide protection and facilitate recovery by mitigating oxidative stress and inflammation, restoring gut microbiota balance, and preserving hormone levels in the context of PS-NPs-induced injury. Full article
(This article belongs to the Section Molecular Pharmacology)
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14 pages, 2177 KiB  
Article
Yamabushitake Mushroom (Hericium erinaceus (Bull.) Pers. 1797) Mycelium Improves Reproductive System Dysfunction in Male Rats Induced by Polystyrene Microplastics
by Yi-Yuh Hwang, Sabri Sudirman, En-Yu Wei, Ruei-Feng Shiu, Zwe-Ling Kong and Deng-Fwu Hwang
Int. J. Mol. Sci. 2025, 26(12), 5735; https://doi.org/10.3390/ijms26125735 - 15 Jun 2025
Viewed by 717
Abstract
The use of plastic products has increased, leading to higher levels of plastic pollution, and it is becoming a major public health concern. Health risks—especially those related to reproductive system dysfunction caused by polystyrene microplastics (PS-MPs)—are emerging issues that require urgent attention. This [...] Read more.
The use of plastic products has increased, leading to higher levels of plastic pollution, and it is becoming a major public health concern. Health risks—especially those related to reproductive system dysfunction caused by polystyrene microplastics (PS-MPs)—are emerging issues that require urgent attention. This study aimed to investigate the effects of erinacine A-enriched Hericium erinaceus mycelium (HE) on high-fat-diet- and PS-MP-induced reproductive system dysfunction in male rats. Reproductive dysfunction was induced by administering a high-fat diet followed by exposure to PS-MPs for six weeks. The results showed that HE treatment significantly reduced nitric oxide levels and enhanced glutathione peroxidase activity. Furthermore, HE supplementation significantly downregulated pro-inflammatory cytokines such as interleukin (IL)-6 and IL-1β. Additionally, HE treatment significantly increased Kiss1 concentration, upregulated follicle-stimulating hormone and testosterone levels, reduced the area of the seminiferous tubule lumen, and prevented a reduction in epithelial thickness. HE treatment also significantly increased sperm count and reduced sperm abnormalities. Based on these findings, HE supplementation helps prevent reproductive system dysfunction by reducing oxidative stress and pro-inflammatory cytokines. Therefore, erinacine A-enriched H. erinaceus mycelium could be considered a potential food supplement or functional food ingredient for the treatment of reproductive or testicular dysfunction. Full article
(This article belongs to the Section Molecular Pharmacology)
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26 pages, 760 KiB  
Review
Male Infertility and Reduced Life Expectancy: Epidemiology, Mechanisms, and Clinical Implications
by Aris Kaltsas, Andreas Koumenis, Marios Stavropoulos, Zisis Kratiras, Dimitrios Deligiannis, Konstantinos Adamos and Michael Chrisofos
J. Clin. Med. 2025, 14(11), 3930; https://doi.org/10.3390/jcm14113930 - 3 Jun 2025
Cited by 1 | Viewed by 1549
Abstract
Male infertility is a prevalent condition affecting approximately 15% of couples worldwide. Recent evidence indicates that, beyond its immediate reproductive implications, male infertility may reflect broader health concerns. Large-scale cohort studies consistently show that men with poorer semen parameters have elevated all-cause mortality [...] Read more.
Male infertility is a prevalent condition affecting approximately 15% of couples worldwide. Recent evidence indicates that, beyond its immediate reproductive implications, male infertility may reflect broader health concerns. Large-scale cohort studies consistently show that men with poorer semen parameters have elevated all-cause mortality compared to fertile counterparts, with a dose-dependent pattern whereby more severe abnormalities correlate with a higher risk of early death. Proposed mechanisms linking infertility to reduced life expectancy encompass genetic, hormonal, and lifestyle factors. For instance, Klinefelter syndrome exemplifies a genetic cause of azoospermia that also predisposes to metabolic syndrome, diabetes, and certain malignancies. Low testosterone, a frequent finding in testicular dysfunction, is implicated in obesity, insulin resistance, and cardiovascular disease, all of which can shorten lifespan. Additionally, psychosocial stress and depression—commonly reported among infertile men—may contribute to health-compromising behaviors. Environmental exposures and socioeconomic factors further compound these risks. Collectively, these data underscore the importance of recognizing male infertility as an early indicator of potentially modifiable health vulnerabilities. A comprehensive evaluation of infertile men should therefore extend beyond fertility assessments to include screening for chronic diseases, hormonal imbalances, and mental health issues. Targeted surveillance for specific cancers (e.g., testicular and prostate) and early interventions—such as lifestyle modifications, appropriate hormonal therapies, and psychosocial support—can improve both reproductive outcomes and long-term well-being. Given these insights, male fertility assessment may serve as a valuable gateway to broader men’s healthcare, prompting proactive strategies that mitigate associated risks and potentially enhance longevity. Full article
(This article belongs to the Special Issue Male Fertility in the Modern Age: Challenges and Opportunities)
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18 pages, 4817 KiB  
Article
Prenatal Bisphenol B Exposure Induces Adult Male Offspring Reproductive Dysfunction via ERα Inhibition-Triggered MHC I-Mediated Testicular Immunological Responses
by Nannan Chen, Xiaotian Li, Shenrui Zhou, Xin Peng, Senlin Xue, Yuetong Liu, Tingwang Jiang and Wei Yan
Toxics 2025, 13(6), 423; https://doi.org/10.3390/toxics13060423 - 22 May 2025
Viewed by 937
Abstract
As an emerging endocrine-disrupting agent and structural analog of bisphenol A (BPA), bisphenol B (BPB) raises significant concerns due to its potential to induce male reproductive toxicity. Despite its presence in maternal bodily fluids, the effects of BPB exposure on the reproductive system [...] Read more.
As an emerging endocrine-disrupting agent and structural analog of bisphenol A (BPA), bisphenol B (BPB) raises significant concerns due to its potential to induce male reproductive toxicity. Despite its presence in maternal bodily fluids, the effects of BPB exposure on the reproductive system and its mechanisms in adult male offspring are poorly understood. By establishing a maternal BPB exposure model in mice, we found that the exposure reduced the relative weights of seminal vesicles and preputial glands, decreased the thickness of the seminiferous epithelium, enlarged the lumen area of seminiferous tubules, and lowered testosterone concentration and synthesis, as well as sperm count in 10-week-old male offspring. Bioinformatic analyses revealed that the differentially expressed genes were significantly associated with major histocompatibility complex I (MHC I)-mediated immunological processes, including immune system processes, antigen processing and presentation of exogenous peptide antigens via MHC class I, and interleukin-2 production. Importantly, molecular docking proposed a potential mechanistic model wherein BPB bound to estrogen receptor α (ERα) suppressed its testicular expression and triggered MHC class I gene overexpression, potentially promoting macrophage infiltration, CD4+/CD8+ T cell activation, and pro-inflammatory cytokine production. Our findings provide critical insights into the adverse effects of maternal BPB exposure on male reproductive development, suggesting that impairments in testicular morphology and spermatogenesis may be attributed to MHC I-mediated immunological responses and hormonal imbalances resulting from inhibited ERα signaling. These results underscore not only the toxicological risks associated with BPB but also potential therapeutic targets for mitigating male reproductive dysfunction. Full article
(This article belongs to the Section Emerging Contaminants)
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