Reproductive toxicology最新文献

{"title":"Late histopathological impacts on the female prostate of gerbils exposed to BPA during pregnancy and lactation","authors":"Lorena Gabriela de Souza ,&nbsp;Thalles Fernando Rocha Ruiz ,&nbsp;Gervásio Evangelista Brito Filho ,&nbsp;Luara Jesus Ferrato ,&nbsp;Simone Jacovaci Colleta ,&nbsp;Ellen Cristina Rivas Leonel ,&nbsp;Sebastião Roberto Taboga","doi":"10.1016/j.reprotox.2025.109013","DOIUrl":"10.1016/j.reprotox.2025.109013","url":null,"abstract":"<div><div>The female prostate is regulated by steroid hormones, mainly androgens and estrogens. Exposure to exogenous chemical compounds leads to effects via endocrine pathways that alter prostate morphophysiology. Bisphenol A (BPA) is a widespread endocrine disruptor, which influences estrogenic pathways, facilitating pre-neoplastic and neoplastic alterations in hormone-sensitive organs. The aim of this study was to evaluate the influence of BPA on the prostate of aged female gerbils exposed to the compound during their gestational and lactational periods. The females were exposed to 50 μg/kg/daily during gestation and lactation, and the analysis was performed in the aged period (18-mo age). Our results showed that BPA increased epithelial alterations, observed by hyperplastic foci and a reduction in atrophies, commonly observed in aged female prostate. These data were supported by phopho-histone H3 immunostaining, that indicated proliferation of the epithelial and stromal compartments, leading to glandular hypertrophy. In addition, a pro-proliferative imbalance was observed through the differential expression of key proteins associated with cell death and proliferation, as well as in the expression of stromal components. Thus, the increase in cell proliferation implies the onset of epithelial alterations, as evidenced by the increased number of hyperplastic foci. The alterations reported after exposure to BPA demonstrated the increased likelihood of proliferative epithelial alterations, with tissue remodeling associated mainly with prostatic stroma.</div></div>","PeriodicalId":21137,"journal":{"name":"Reproductive toxicology","volume":"137 ","pages":"Article 109013"},"PeriodicalIF":2.8,"publicationDate":"2025-07-25","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144733008","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Tattoo exposure and biomarkers of male fecundity: A cross-sectional study among young Danish males","authors":"Mette Møller Dornfeldt ,&nbsp;Sidsel Dan Hull ,&nbsp;Christel Nielsen ,&nbsp;Emelie Rietz Liljedahl ,&nbsp;Cecilia Høst Ramlau-Hansen ,&nbsp;Anne Gaml-Sørensen ,&nbsp;Gunnar Toft ,&nbsp;Jens Peter Bonde ,&nbsp;Karin Sørig Hougaard ,&nbsp;Sandra Søgaard Tøttenborg","doi":"10.1016/j.reprotox.2025.109009","DOIUrl":"10.1016/j.reprotox.2025.109009","url":null,"abstract":"<div><h3>Background</h3><div>Tattoo inks are mixtures of organic and inorganic color pigments and having a tattoo may be adversely associated with biomarkers of male fecundity.</div></div><div><h3>Objective</h3><div>To examine the association between tattoo exposure and biomarkers of male fecundity.</div></div><div><h3>Methods</h3><div>Participants were young adult Danish males (aged 18–21 years) sampled from the Danish National Birth Cohort. Upon recruitment in 2017–2019, participants answered a comprehensive questionnaire including information on tattoo exposure and provided a semen and blood sample. We applied a negative binomial regression model to estimate percentage differences (95 % confidence intervals [CI]) in semen characteristics, testicular volume, and reproductive hormone levels between tattooed and non-tattooed participants.</div></div><div><h3>Results</h3><div>Among the 1045 participants included in this study, 174 (17 %) had at least one tattoo and most tattooed participants (84 %) had tattoo(s) in only black color. About half (53 %) had one tattoo, 21 % had two tattoos, and 26 % had three or more tattoos. We observed no association between either number or color scheme of tattoo(s) relative to semen characteristics or reproductive hormone levels. Having a tattoo was associated with 6 % (95 % CI: 0, 12) larger testicular volume, but since testicular volume was measured by the participants themselves, this finding may be due to differential misclassification bias. Across all outcomes the crude and adjusted models were comparable.</div></div><div><h3>Conclusion</h3><div>Overall, we found no support for adverse associations between tattoo exposure and biomarkers of male fecundity, but studies with more details on tattoo exposure and longer follow-up of participants are needed before firm conclusions can be drawn.</div></div>","PeriodicalId":21137,"journal":{"name":"Reproductive toxicology","volume":"137 ","pages":"Article 109009"},"PeriodicalIF":2.8,"publicationDate":"2025-07-23","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144718261","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Oxidative stress: Oocyte quality and infertility","authors":"Ismat Ara Begum","doi":"10.1016/j.reprotox.2025.109011","DOIUrl":"10.1016/j.reprotox.2025.109011","url":null,"abstract":"<div><div>Infertility affects a significant proportion of couples worldwide, with female reproductive dysfunction contributing to nearly half of these cases. Oxidative Stress (OS), characterized by an imbalance between Reactive Oxygen Species (ROS) production and antioxidant defenses, has emerged as a critical factor influencing oocyte quality and female fertility. This review examines the origins of OS both in vivo and in vitro, highlighting mitochondria and granulosa cells as primary sources, and explores the impact of ovarian aging, obesity, hyperoxic culture conditions, and environmental exposures such as cigarette smoke, endocrine-disrupting chemicals, and controlled ovarian stimulation drugs. This work further explores how OS adversely affects oocyte quality through mechanisms including mitochondrial dysfunction, follicular atresia, meiotic errors, DNA damage, telomere shortening, and reduced fertilization rates. Additionally, this review explores reproductive disorders associated with OS, including polycystic ovary syndrome, endometriosis, premature ovarian insufficiency, and miscarriage. The implications of OS in ART are also addressed, emphasizing the need for strategies to mitigate oxidative damage in both clinical and environmental contexts. This review underscores the significance of OS in female reproductive health, paving the way for potential therapeutic interventions to enhance fertility outcomes.</div></div>","PeriodicalId":21137,"journal":{"name":"Reproductive toxicology","volume":"137 ","pages":"Article 109011"},"PeriodicalIF":3.3,"publicationDate":"2025-07-23","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144703865","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Ameliorative effect of curcumin loaded nanoliposomes: A Promising bioactive formulation, against the DBP-induced testicular damage","authors":"Manal R. Bakeer ,&nbsp;Maha M. Rashad ,&nbsp;Fady Sayed Youssef ,&nbsp;Omaima Ahmed ,&nbsp;Seham Samir Soliman ,&nbsp;Ghada E. Ali","doi":"10.1016/j.reprotox.2025.109008","DOIUrl":"10.1016/j.reprotox.2025.109008","url":null,"abstract":"<div><div>Plasticizers are widely employed in various applications. Therefore, these products may have an impact on the biological systems of humans and other organisms. Thus, seeking a potent and eco-friendly protective agent becomes a great challenge. The current study investigated the underlying molecular mechanism associated with the protective effect of curcumin-loaded nanoliposomes (CUR nanoliposomes) against DBP-induced testicular damage. A total of twenty-four adult male rats were split up into four groups: the control group, the CUR nanoliposomes-treated group (100 mg/kg/day by oral gavage), the DBP-treated group (500 mg/kg/day by oral gavage), and the last group that received both treatments simultaneously for 60 days. The results showed that DBP exposure induced Leydig cell damage and testicular injury, represented by decreased serum sex hormone levels, downregulation of <em>INSL3</em> gene expression, elevated testicular LDH, and aberrant sperm rate, as well as pathologically abnormal testicular anatomy. These testicular injuries are associated with redox state imbalance (elevated MDA, reduced CAT activity, and downregulation of <em>Nrf2</em> and <em>SOD</em> gene expression), elevated apoptosis biomarkers (CASP3 and CASP9), and dysregulation of the PI3K/AKT/mTOR pathway. Co-administration of CUR nanoliposomes succeeded in reversing DBP-induced testicular damage. CUR nanoliposome-induced testicular protection could be attributed to the modulation of the PI3K/AKT/mTOR pathway.</div></div>","PeriodicalId":21137,"journal":{"name":"Reproductive toxicology","volume":"137 ","pages":"Article 109008"},"PeriodicalIF":3.3,"publicationDate":"2025-07-22","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144703800","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Effects of cannabidiol, cannabichromene, cannabidivarin, cannabigerol and cannabinol in endometrial cells: Implications for endocrine and senescence modulation","authors":"Patrícia Alves,&nbsp;Cristina Amaral,&nbsp;Bruno M. Fonseca,&nbsp;Luísa G. Sousa,&nbsp;Natércia Teixeira,&nbsp;Georgina Correia-da-Silva","doi":"10.1016/j.reprotox.2025.109006","DOIUrl":"10.1016/j.reprotox.2025.109006","url":null,"abstract":"<div><div>Throughout a woman’s menstrual cycle, endometrial stromal cells (ESCs) undergo cyclic morphological and functional alterations, involving proliferation, differentiation and senescence, modulated in part by steroid hormones and the endocannabinoid system. Disruptions in these processes can lead to endometrial conditions, like endometriosis or miscarriage. In this work, we examined the impact of the phytocannabinoids cannabidiol (CBD), cannabichromene (CBC), cannabidivarin (CBDV), cannabigerol (CBG) and cannabinol (CBN) at 2 µM, by using the St-T1b cell line, a representative model of ESCs. CBDV, CBD and CBN increased <em>ESR1</em> transcription, while it was decreased by CBG. Estrogen receptor α (ER) protein was reduced by CBG and CBN. ER activation, assessed via <em>TFF1</em> expression, was promoted by all cannabinoids except CBN, which suppressed it. Progesterone receptor gene expression increased for CBC, CBDV and CBG treatments, decreasing for CBN. Furthermore, androgen receptor (AR) transcription was upregulated by CBC and CBN, with protein levels increased only by CBN. All the cannabinoids inhibited AR activation. CBN enhanced AKT and ERK1/2 phosphorylation and upregulated <em>AREG</em> expression. Senescence-associated markers <em>YPEL3</em> and <em>LMNB1</em> were modulated by CBC, CBD, and CBN, accompanied by increased β-galactosidase accumulation. Additionally, CBC and CBD upregulated NAPE-PLD mRNA levels, the anandamide synthesis enzyme, although CBC and CBN reduced its protein expression. CBDV increased gene and protein expression of FAAH, the anandamide degrading enzyme. These results suggest that phytocannabinoids may disrupt the interplay between the endometrial endocrine signaling and the endocannabinoid system, as well as modulate senescence in ESCs, potentially affecting female fertility.</div></div>","PeriodicalId":21137,"journal":{"name":"Reproductive toxicology","volume":"137 ","pages":"Article 109006"},"PeriodicalIF":3.3,"publicationDate":"2025-07-22","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144695178","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Maternal application of tropical antifungal medication is associated with reduced steroid hormone levels during minipuberty and shorter anogenital distance in offspring from 3 months to 9 years of age: Odense Child Cohort","authors":"Sarah Munk Andreasen ,&nbsp;Anna-Patricia Iversen ,&nbsp;Lars Christian Lund ,&nbsp;Margit Bistrup Fischer ,&nbsp;Anna-Maria Andersson ,&nbsp;Naja Kamuk Rauer ,&nbsp;Gylli Mola ,&nbsp;Anders Juul ,&nbsp;Casper P. Hagen ,&nbsp;Tina Kold Jensen","doi":"10.1016/j.reprotox.2025.109007","DOIUrl":"10.1016/j.reprotox.2025.109007","url":null,"abstract":"<div><div>Vaginal candidiasis affects about 20 % of pregnant women and is usually treated with over-the-counter topical antifungal medication (azoles). Vaginal or transdermal application of azoles are absorbed and detectable in circulation. Azoles inhibit CYP51, which is crucial for the integrity of fungal cellular membranes. However, cell cultures have shown that azoles also affect steroidogenesis. This study investigated maternal antifungal application during pregnancy and the association with reproductive hormones during <em>minipuberty</em> and anogenital distance (AGD) the in the offspring from infancy to 9 years of age. In the Odense Child Cohort (2010–2012), women completed questionnaires about antifungal application during pregnancy. Serum concentrations of luteinising hormone (LH), follicle-stimulating hormone (FSH), testosterone (T), estrone (E1), estradiol (E2), Δ4-androstenedione (adione), 17α-hydroxyprogesterone (17-OHP) and dehydroepiandrosterone-sulphate (DHEAS) were analysed in 454 infants at 3 months. AGD was assessed at 3, 18 months and 3, 5, 7 and 9 years of age, with 1792 measurements. Topical antifungal application during pregnancy was reported by 35 women. In boys, maternal application before GW 19 was associated with shorter AGD as well as lower adrenal hormone levels. In girls, application before GW 19 was associated with longer AGD and lower reproductive and adrenal hormone levels, while application after GW 19 was associated with shorter AGD, while hormone levels did not differ. Given the small number of cases, the findings should be interpreted with caution. The widespread use of over-the-counter antifungals appears to affect AGD and hormone production in offspring, which is concerning and may have long-term consequences for reproductive health.</div></div>","PeriodicalId":21137,"journal":{"name":"Reproductive toxicology","volume":"137 ","pages":"Article 109007"},"PeriodicalIF":3.3,"publicationDate":"2025-07-22","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144695177","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Lipopolysaccharide-induced inflammation modulates testicular kisspeptin system in mice","authors":"Jaldhi ,&nbsp;Shweta ,&nbsp;Shashank Kumar Maurya ,&nbsp;Amrita Bakshi","doi":"10.1016/j.reprotox.2025.109005","DOIUrl":"10.1016/j.reprotox.2025.109005","url":null,"abstract":"<div><div>Kisspeptin, a neuropeptide hormone, plays an indispensable role in regulating reproduction. Acting upstream of gonadotropin-releasing hormone, it controls gonadotropin release, and concomitant gonadal functions, and in turn, is regulated by gonadal steroid hormones. Nevertheless, expression of kisspeptin (Kiss1) and its receptor (Kiss1r) is reported in tissues other than hypothalamus, including testes. Since immune-challenged conditions lead to compromised reproductive functions, the present work emphasizes on investigating regulation of the testicular kisspeptin system in adult mice by lipopolysaccharide (LPS)-induced inflammation. <em>In vivo</em> chronic treatment of LPS for 7 days caused irregularly-shaped seminiferous tubules with reduced perimeter, diameter and cross-sectional area, distorted arrangement of spermatogenic cells, disrupted connective tissue leading to increased interstitial space and reduced sperm count. Further, elevated expression level of pro-inflammatory cytokine, <em>Tnfα,</em> in the testis validated the induction of inflammation. Regarding the kisspeptin system, a significant increase in testicular Kiss1 but a decrease in Kiss1r expression was observed at both gene and protein levels, implying a possible compensatory role of testicular kisspeptin to control reproductive functions under an infectious state. Further, an <em>in vitro</em> treatment of testicular fragments with LPS was conducted for 3 h and 6 h to understand the direct effect of inflammation on the testicular kisspeptin system. An increased <em>Tnfα</em> but decreased <em>Tgfβ1</em> expression was observed at both time points. At the transcript level, <em>Kiss1</em> showed a reduced expression at 6 h but no change at 3 h of LPS treatment. Regarding <em>Kiss1r</em>, an increased expression at 3 h but decreased at 6 h was seen. At the protein level, decreased levels of testicular Kiss1 was observed at both the time points while Kiss1r exhibited no significant change. Hence, the present work demonstrated modulation of the testicular kisspeptin system by LPS-induced inflammation.</div></div>","PeriodicalId":21137,"journal":{"name":"Reproductive toxicology","volume":"137 ","pages":"Article 109005"},"PeriodicalIF":3.3,"publicationDate":"2025-07-22","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144703908","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Maternal smoking affects human fetal X-inactivation","authors":"Sanam Zeib Khan ,&nbsp;Linn Salto Mamsen ,&nbsp;Erik Ernst ,&nbsp;Esben Budtz-Jørgensen ,&nbsp;Claus Yding Andersen ,&nbsp;Niels Tommerup","doi":"10.1016/j.reprotox.2025.109010","DOIUrl":"10.1016/j.reprotox.2025.109010","url":null,"abstract":"<div><div>Females inactivate one of their two X-chromosomes in each cell before implantation, at a time where any factor that affect the number of these primordial cells may lead to deviation from the usual random choice. Thus, non-random (skewed) X-inactivation may occur due to early stochastic effects in the limited primordial pool size. The primodial pool size can be calculated from the variance of the ratio between the unmethylated and methylated CAG-repeats within exon 1 of the androgen receptor gene (<em>AR</em>) corresponding to the active and inactive X-chromosome (X-inactivation (XI)-ratio), respectively. Since maternal smoking during pregnancy is associated with a general growth inhibition and a reduced number of fetal gonadal cells, we have tested the XI-ratios in tissues obtained from fetuses of smoking (n = 8) and non-smoking (n = 10) mothers in connection with legal termination of the pregnancy. A tighter distribution of XI-ratios was seen in tissues from fetuses in the smoking group. Combined with more skewed X-inactivation (&gt;=80 %) and a higher mean XI-ratio in the fetal samples from pregnancies of non-smoking mothers, this support a larger pool of primordial cells in fetuses exposed to smoking, suggesting that smoking during pregnancy delays fetal X inactivation.</div></div>","PeriodicalId":21137,"journal":{"name":"Reproductive toxicology","volume":"137 ","pages":"Article 109010"},"PeriodicalIF":2.8,"publicationDate":"2025-07-22","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144708590","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Ever cannabis use and biomarkers of male fecundity – A study in the Danish National Birth Cohort","authors":"Georges Khoury ,&nbsp;Sidsel Dan Hull ,&nbsp;Cecilia Høst Ramlau-Hansen ,&nbsp;Anne Gaml Sørensen ,&nbsp;Karin Sørig Hougaard ,&nbsp;Kajsa Ugelvig Petersen ,&nbsp;Gunnar Toft ,&nbsp;Laura Deen ,&nbsp;Jens Peter Bonde ,&nbsp;Sandra Søgaard Tøttenborg","doi":"10.1016/j.reprotox.2025.109004","DOIUrl":"10.1016/j.reprotox.2025.109004","url":null,"abstract":"<div><h3>Background</h3><div>Reports of low semen quality have led to investigations of potential risk factors, including cannabis use. Cannabis affects the endocannabinoid system, which in part regulates spermatogenesis and hormonal balance, but evidence on its impact on male reproductive health remains inconsistent.</div></div><div><h3>Objective</h3><div>This study examined the associations between ever cannabis use and biomarkers of male fecundity in a large cohort of young Danish men incorporating detailed information on their concurrent health behaviors and potential confounding factors during fetal life, a key limitation of previous studies.</div></div><div><h3>Methods</h3><div>We used data from the Fetal Programming of Semen Quality cohort, a sub cohort of 1058 young men born to women enrolled in the Danish National Birth Cohort. Cannabis use was self-reported via an online questionnaire before a clinical examination. Semen samples were collected and analyzed for volume, concentration, total count, motility, morphology, and DNA fragmentation. Hormone levels were measured from venous blood samples. Testicular volume was self-assessed using a Prader Orchidometer.</div></div><div><h3>Results</h3><div>Among participants included in the analytical sample, 324 (31 %) had never used cannabis and 721 (59 %) had used cannabis at least once. We observed no association between ever cannabis use and male fecundity biomarkers, except for a slight indication of higher follicle-stimulating hormone (FSH) levels among ever cannabis users (8 % [95 % CI: −2, 20]).</div></div><div><h3>Conclusion</h3><div>While we found no associations between ever cannabis use and most biomarkers of fecundity in young men, the higher FSH levels among ever cannabis users could suggest early signs of impaired testicular function. However, this needs to be confirmed in studies with a more comprehensive assessment of cannabis exposure.</div></div>","PeriodicalId":21137,"journal":{"name":"Reproductive toxicology","volume":"137 ","pages":"Article 109004"},"PeriodicalIF":3.3,"publicationDate":"2025-07-20","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144691343","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Unravelling the potential mechanisms of nano- and microplastic toxicity to the male reproductive system: A systematic review","authors":"Paloma da Cunha de Medeiros ,&nbsp;Aline Gabrielle Gomes da Silva ,&nbsp;Ana Beatriz Silva Angelo ,&nbsp;Maria Joana Nogueira de Moura ,&nbsp;Unnikrishnan Kannan ,&nbsp;Mary Gregory ,&nbsp;Julie Dufresne ,&nbsp;Cibele dos Santos Borges ,&nbsp;Daniel G. Cyr","doi":"10.1016/j.reprotox.2025.109002","DOIUrl":"10.1016/j.reprotox.2025.109002","url":null,"abstract":"<div><div>The ever-increasing presence of microplastic and nanoplastic (MPs/NPs) particles in the natural environment, organisms, and a wide variety of health products, cosmetics, pharmaceuticals, and foods consumed by humans is a global concern. In recent years, research efforts have shifted towards identifying human exposure and risks associated with MPs/NPs, as well as unravelling the mechanisms underlying their toxicity. This systematic review examined the literature regarding the effects of MPs/NPs on the male reproductive system, focusing on the testis, epididymis, and their associated barriers. Research, conducted primarily on rodents, demonstrated that MPs/NPs of various chemical compositions can bioaccumulate in the testis and epididymis, identifying these organs as key targets of plastic particle toxicity. Several studies using rodent models reported alterations in the blood-testis barrier, a crucial structure necessary for proper spermatogenesis. Additionally, multiple studies observed increased apoptosis of germ cells, malformations of spermatozoa, and decreased sperm motility, which is typically acquired during epididymal transit. Exposure to MPs/NPs disrupted Sertoli and Leydig cell function, leading to hormone imbalance. This is likely due to a combination of oxidative stress, inflammation, and disruption of the blood-testis barrier. These effects appear to be influenced by a combination of particle characteristics, including size, shape, chemical composition, surface properties, and exposure route. Larger MPs often cause greater structural damage, while smaller NPs more readily penetrate tissues and trigger molecular disruptions. Understanding how these particles alter male reproductive functions is essential for evaluating their full impact on fertility.</div></div>","PeriodicalId":21137,"journal":{"name":"Reproductive toxicology","volume":"137 ","pages":"Article 109002"},"PeriodicalIF":3.3,"publicationDate":"2025-07-18","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144668209","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}