Reproductive toxicology最新文献

{"title":"In utero exposure to estrogenic bisphenol analogues increases mammary tissue stiffness","authors":"Jillian M. Poska ,&nbsp;Clarissa Wormsbaecher ,&nbsp;Brittney M. Cumbia ,&nbsp;Madeline R. Price ,&nbsp;Marcos Cortes-Medina ,&nbsp;Jacob Holter ,&nbsp;Shashwat Agarwal ,&nbsp;Xiaokui Molly Mo ,&nbsp;Jonathan W. Song ,&nbsp;Craig J. Burd","doi":"10.1016/j.reprotox.2025.108974","DOIUrl":"10.1016/j.reprotox.2025.108974","url":null,"abstract":"<div><div>In utero exposures to estrogenic endocrine disrupting compounds (EDCs) can increase breast cancer risk in adulthood. It has previously been shown that the estrogenic plasticizer bisphenol A (BPA) alters development of the mammary gland and increases both mammary gland stiffness and tumor susceptibility in rodent models following in utero exposure. Because of its endocrine disrupting properties, BPA has been substituted with structural analogues with varying abilities to activate estrogen receptor alpha (ERα). However, the impact of in utero exposure to many of these analogues is unknown. In the present study, we aimed to analyze the impact of bisphenol analogues on collagen deposition and mammary gland stiffness and characterize mammary epithelial development following exposure to these compounds. With the exception of bisphenol S, all analogues significantly increased mammary gland stiffness at a 25 µg/kg body weight dose in a manner that correlated to estrogenic activity. In contrast, significant effects on epithelial development endpoints were limited and did not follow a clear pattern. These results add to the growing literature on the hazard of bisphenol analogues and support the idea that these compounds promote abnormal mammary gland development. Furthermore, these data support a model that bisphenol compounds induce a microenvironment that may promote breast cancer development in an estrogen-dependent manner.</div></div>","PeriodicalId":21137,"journal":{"name":"Reproductive toxicology","volume":"136 ","pages":"Article 108974"},"PeriodicalIF":3.3,"publicationDate":"2025-06-11","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144291079","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":"Impact of particulate matter 2.5 on placental ultrastructure including mitochondrial damage through oxidative stress","authors":"Gain Lee ,&nbsp;Jung Mi Han ,&nbsp;Young-Ah You ,&nbsp;Yoon-Young Go ,&nbsp;Sunwha Park ,&nbsp;Young Min Hur ,&nbsp;Soo Min Kim ,&nbsp;Ki-Hwan Han ,&nbsp;Young Ju Kim","doi":"10.1016/j.reprotox.2025.108973","DOIUrl":"10.1016/j.reprotox.2025.108973","url":null,"abstract":"<div><h3>Introduction</h3><div>Particulate matter 2.5 (PM_2.5) refers to fine particles with a diameter of less than 2.5μm, associated with adverse pregnancy outcomes. The study aims to determine whether elevated prenatal PM_2.5 levels were associated with alterations in the ultrastructure of the placenta and mitochondria, potentially linked to oxidative stress.</div></div><div><h3>Methods</h3><div>The placental samples were collected from the Air Pollution on Pregnancy Outcome (APPO) cohort and were classified into two groups based on PM_2.5 exposure levels: the High group (&gt; 15 μg/m³; n = 9) and the Low group (≤ 15 μg/m³; n = 8). Transmission electron microscopy was used to assess the ultrastructure of the placenta, specifically the syncytiotrophoblast area. The structure of the mitochondria in the fetal capillaries was also analyzed. Malondialdehyde (MDA) and superoxide dismutase 2 (SOD2) were quantified by using enzyme-linked immunosorbent assays (ELISA).</div></div><div><h3>Results</h3><div>The High group placenta showed ultrastructural changes including microvilli loss, basement membrane thickening, vacuolation and swollen endoplasmic reticulum (ER). Microvilli were significantly shortened and lost in the High group (<em>P</em> &lt; 0.005). Swollen vacuoles, ER stress, and basement membrane thickening were observed in High group syncytiotrophoblast (<em>P</em> &lt; 0.005). Mitochondria in fetal capillaries from the High group were also damaged, showing disrupted double membranes and cristae (<em>P</em> &lt; 0.05). MDA and SOD2 levels were significantly upregulated in the High group (<em>P</em> &lt; 0.05).</div></div><div><h3>Conclusion</h3><div>Prenatal exposure to PM_2.5 may be associated with alterations of placental ultrastructure and mitochondrial damage in fetal capillaries, potentially mediated by oxidative stress, as indicated by elevated levels of MDA and SOD2.</div></div>","PeriodicalId":21137,"journal":{"name":"Reproductive toxicology","volume":"136 ","pages":"Article 108973"},"PeriodicalIF":3.3,"publicationDate":"2025-06-10","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144263503","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":"Limited passage and functional effects of polystyrene micro- and nanoplastics in a physiologically-relevant in vitro human placental co-culture model","authors":"Jeske van Boxel ,&nbsp;Sandra M. Nijmeijer ,&nbsp;Manuel T. Heinzelmann ,&nbsp;Sebastian Rupp ,&nbsp;Majorie B.M. van Duursen","doi":"10.1016/j.reprotox.2025.108956","DOIUrl":"10.1016/j.reprotox.2025.108956","url":null,"abstract":"<div><div>The placenta plays a crucial role during pregnancy, yet effective <em>in vitro</em> models for placental toxicity testing are limited. In this study, a Transwell co-culture model combining BeWo b30 and HUVEC cells was developed and characterized, and used to study the transport and effects of polystyrene micro- and nanoplastics (PS-MNPs). After 72 h, 8.7 % of 50 nm and 1.2 % of 200 nm of fluorescent (F)PS-MNPs were detected on the basolateral side, while 1000 nm FPS-MNPs were undetectable. Confocal microscopy showed the uptake of 50 and 200 nm FPS-MNPs by the BeWo b30 and HUVEC cell layer, whereas the 1000 nm FPS-MNPs were only found within the BeWo b30 cell layer. Exposure to PS-MNPs (sizes of 50, 200 and 1000 nm at concentrations of 1–10 µg/mL) did not result in an effect on mitochondrial activity, oxidative stress and gene expression of several functional markers and steroidogenic enzymes. However, LC/MS-MS analysis of the culture media showed a decrease of 17 % in the level of 17-alpha-estradiol after 72-hour exposure to 1 µg/mL 50 nm PS-MNPs compared to vehicle control. Overall, our data showed limited effects of PS-MNPs on placental cell function <em>in vitro</em>, but FPS-MNPs were internalized and detected on the basolateral side in the co-culture. This warrants further studies on effects of MNPs on placental cell function, and particularly steroidogenesis, to assess the potential effects of MNPs during pregnancy.</div></div>","PeriodicalId":21137,"journal":{"name":"Reproductive toxicology","volume":"136 ","pages":"Article 108956"},"PeriodicalIF":3.3,"publicationDate":"2025-06-06","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144249417","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":"Glycine intervention can alleviate imidacloprid-induced spermatogenic damage in rats","authors":"Zhihui Zhang ,&nbsp;Weilong Cheng ,&nbsp;Junsong Xiao ,&nbsp;Yixuan Li ,&nbsp;Guoping Zhao ,&nbsp;Yanbo Wang","doi":"10.1016/j.reprotox.2025.108970","DOIUrl":"10.1016/j.reprotox.2025.108970","url":null,"abstract":"<div><div>Imidacloprid (IMI) is the first neonicotinoid pesticide with documented associations to substantial harm in multiple organs, notably impacting spermatogenesis in the reproductive system. Given the inevitable exposure to pesticides like IMI through dietary sources, employing dietary interventions to counteract the spermatogenic system damage caused by IMI exposure is a promising approach. Glycine (Gly), an amino acid abundantly found in various dietary sources, has been observed to be diminished in rat individuals exposed to IMI. The current study aims to explore the potential of Gly diet supplementation to alleviate the reproductive system damage caused by IMI. Utilizing a rat model subjected to IMI exposure, interventions with 2.5% and 5% dietary glycine were implemented. The findings revealed that with the dose increase of Gly intervention, testicular tissue morphology was improved, and the number of sperm in the testicle was also increased significantly <em>(p</em> &lt; 0.01). Gly regulated the expression of key enzymes in testosterone hormone synthesis, including P450c17, P450scc, 17β-HSD, and 3β-HSD, enhancing the enzymatic activity of testicular support cells, particularly evident with high-dose Gly intervention. Furthermore, Gly intervention reduced IMI-induced oxidative stress, thereby ameliorating spermatogenic impairment as indicated by decreased superoxide dismutase activity and increased glutathione peroxidase activity. In conclusion, this study underscores the potential of Gly supplementation as a beneficial strategy to mitigate spermatogenic injury caused by IMI exposure in male rats, highlighting its potential as a dietary intervention for protecting against reproductive toxicity associated with pesticide exposure.</div></div>","PeriodicalId":21137,"journal":{"name":"Reproductive toxicology","volume":"136 ","pages":"Article 108970"},"PeriodicalIF":3.3,"publicationDate":"2025-06-03","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144226456","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":"The use of pregabalin in early pregnancy and major congenital malformations: A systematic review and meta-analysis","authors":"Marina Atzenhoffer,&nbsp;Audrey Peron,&nbsp;Cyndie Picot,&nbsp;Michel Cucherat,&nbsp;Judith Cottin","doi":"10.1016/j.reprotox.2025.108958","DOIUrl":"10.1016/j.reprotox.2025.108958","url":null,"abstract":"<div><div>Pregabalin is an antiseizure medication indicated for a wide range of medical conditions other than epilepsy, such as neuropathic pain and generalized anxiety disorder. Preclinical observations have suggested reproductive toxicity for this agent, with skeletal malformations and growth retardation. Human data is sparse and studies lead to contradictory results. Our objective was to conduct a systematic review and meta-analysis on the risk of major congenital malformations (MCMs) associated with pregabalin use in monotherapy during the first trimester of pregnancy. References were identified through a snowballing approach until 2015 and through electronic databases (MEDLINE and Embase) from 2015 to June 30, 2024. All comparative studies including pregnant women exposed to pregabalin monotherapy during the first trimester of pregnancy were included. Two reviewers independently screened citations for eligibility and extracted data using a proprietary collaborative Web-based meta-analysis platform (metaPreg.org). The risk of MCMs between pregabalin exposed and non-exposed pregnancies, and its 95 % confidence interval were estimated using a random effects model. Seven studies, retrospective and prospective cohorts, included data from 3,336,224 pregnant women. Among them, 701 were exposed to pregabalin monotherapy during the first trimester of pregnancy. There was no significant association between the risk of MCMs and first trimester exposure to pregabalin monotherapy (pooled OR 1.79, 95 %CI [0.80; 3.99]). Some between-study heterogeneity was observed (I² = 51 %;). No significant association between pregabalin monotherapy and the risk of MCMs was found. This result should be interpreted with caution given the small number of studies included and their critical risk of bias.</div></div>","PeriodicalId":21137,"journal":{"name":"Reproductive toxicology","volume":"136 ","pages":"Article 108958"},"PeriodicalIF":3.3,"publicationDate":"2025-06-03","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144220901","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":"Associations between urinary phthalate metabolite mixtures, semen quality, and serum reproductive hormone levels in Japanese men seeking fertility treatment","authors":"Yuki Mizuno ,&nbsp;Kazumitsu Yamasaki ,&nbsp;Masahiro Uchida ,&nbsp;Teruaki Iwamoto ,&nbsp;Shoko Konishi","doi":"10.1016/j.reprotox.2025.108957","DOIUrl":"10.1016/j.reprotox.2025.108957","url":null,"abstract":"<div><div>Phthalate mixtures may adversely affect men’s reproductive functioning. This study aimed to analyze the association between exposure to phthalate mixtures, semen quality, and reproductive hormone concentrations in Japanese men seeking fertility treatment. This cross-sectional study analyzed data from 197 Japanese adult males who visited clinics for infertility consultations in 2020 and 2021. Semen samples were collected to measure volume, sperm count, sperm concentration, and motility. Spot urine samples were collected to quantify phthalate monoesters, specifically phthalate diester metabolites, using liquid chromatography-tandem mass spectrometry. Serum concentrations of testosterone, estradiol, luteinizing hormone, follicle-stimulating hormone, and prolactin were obtained from clinical records. Three statistical methods—weighted quantile sum regression, quantile g-computation, and Bayesian kernel machine regression—were applied. Urinary concentrations of phthalate metabolite mixtures were positively associated with sperm motility, with monoethyl phthalate being the most important contributor to the observed association. No significant associations were found between phthalate mixtures and semen volume, sperm count, or concentration. These associations were consistent across all three statistical methods. Higher urinary concentrations of phthalate metabolite mixtures were associated with lower testosterone and higher prolactin concentrations in serum; however, there were no significant associations between phthalate mixtures or individual phthalate metabolites and estradiol, follicle-stimulating hormone, or luteinizing hormone concentrations. Higher exposure to phthalate mixtures may be associated with increased sperm motility and serum prolactin and reduced serum testosterone concentrations. Overall, these findings suggest that even at a relatively low level, exposure to phthalate mixtures may affect male reproductive health.</div></div>","PeriodicalId":21137,"journal":{"name":"Reproductive toxicology","volume":"136 ","pages":"Article 108957"},"PeriodicalIF":3.3,"publicationDate":"2025-06-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144216756","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":"The inhibition of prostaglandin production during ovulation by exposure to a phthalate mixture is circumvented by cAMP analogue supplementation in a human granulosa cell model","authors":"Patrick R. Hannon ,&nbsp;Katie L. Land ,&nbsp;Hong Xu ,&nbsp;James W. Akin ,&nbsp;Thomas E. Curry","doi":"10.1016/j.reprotox.2025.108968","DOIUrl":"10.1016/j.reprotox.2025.108968","url":null,"abstract":"<div><div>Exposure to individual phthalates disrupts ovarian function; however, the direct effects of phthalate mixture exposure on ovulation is unknown, especially in women. Human granulosa cells were used to test the hypothesis that exposure to a phthalate mixture (PHTmix; derived from women’s urinary phthalate levels) disrupts the function of prostaglandins (PGs), which are vital mediators of ovulation. Additionally, cAMP supplementation was tested as a method to circumvent phthalate toxicity. Granulosa cells from women undergoing <em>in vitro</em> fertilization were acclimated in culture to regain responsiveness to human chorionic gonadotropin (hCG; clinical luteinizing hormone analogue). Granulosa cells were treated with or without hCG, with or without PHTmix (1–500 µg/ml; DMSO=vehicle control), and with or without 8-Br-cAMP (stable cAMP analogue) for 6–36 hr. Exposure to hCG+PHTmix decreased ovulatory PGE₂ and PGF_2α levels when compared to hCG. The mechanism by which the PHTmix decreased PG levels was via decreased synthesis (decreased <em>PTGS2</em> and <em>PTGES</em> levels) and increased metabolism (increased <em>AKR1C1</em>, <em>AKR1C3</em>, and <em>HPGD</em> levels). Exposure to hCG+PHTmix also impaired PG function by altering levels of PG transporters (<em>ABCC4</em> and <em>SLCO2A1</em>) and receptors (<em>PTGER2</em>, <em>PTGER3</em>, and <em>PTGFR</em>) when compared to hCG. Supplementation with cAMP in the hCG+PHTmix 500 µg/ml group restored PGE₂ and PGF_2α levels comparable to and beyond hCG control levels. These findings suggest that phthalates inhibit the ovulatory increase in PGs in human granulosa cells via decreased synthesis and increased metabolism. Restored PG levels with cAMP supplementation further establishes a mechanism of toxicity by providing demonstration of a potential cellular target of phthalate-induced ovulatory defects in women.</div></div>","PeriodicalId":21137,"journal":{"name":"Reproductive toxicology","volume":"136 ","pages":"Article 108968"},"PeriodicalIF":3.3,"publicationDate":"2025-05-31","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144209390","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":"Use of serotonin reuptake inhibitors (SSRIs) and serotonin and norepinephrine reuptake inhibitors (SNRIs) during pregnancy: Effect on fetal growth and long-term reproductive outcomes","authors":"Debarshi Sarkar ,&nbsp;Souvik Mandal ,&nbsp;Srinwanti Bandyopadhyay ,&nbsp;Sayan Bose ,&nbsp;Jyoti Parkash ,&nbsp;Shio Kumar Singh","doi":"10.1016/j.reprotox.2025.108960","DOIUrl":"10.1016/j.reprotox.2025.108960","url":null,"abstract":"<div><div>Anxiety and depression during pregnancy are recognized as major public health concerns. Depression and anxiety, if untreated, severely affect both mother and the fetus, especially during pregnancy. Selective serotonin reuptake inhibitors (SSRIs) and serotonin-norepinephrine reuptake inhibitors (SNRIs) are frequently prescribed drugs to manage above conditions during pregnancy. Although these medications affect the levels of neurotransmitters, research indicates their potential impact on development of the fetus. Studies on maternal exposure to SSRIs and SNRIs show possible risks of offspring's congenital cardiovascular abnormalities and anomalies of the kidney and digestive system. Maternal exposure to selective SSRIs and SNRIs during pregnancy has been associated with certain adverse perinatal outcomes, including preterm birth, low birth weight, and neonatal adaptation syndrome. Exposure to SSRIs and SNRIs also increases the possible risk of persistent pulmonary hypertension in the newborn. However, evidence regarding long-term neurodevelopmental outcomes remains inconclusive, with studies showing mixed results. Therefore, based on the available data, it is hypothesized that these drugs may potentially have direct or indirect effects on reproductive outcomes of the progeny. Because of the increasing occurrence of maternal depression worldwide and the consequent usage of SSRIs and SNRIs, there is an urgent need for additional data to better understand the risk of developmental toxicity related to the use of these antidepressants during pregnancy. This review, therefore, aims to examine the effects of SSRIs and SNRIs exposure during pregnancy on fetal growth, postnatal development and long-term reproductive outcomes of the progeny with regard to a careful consideration of better treatment options.</div></div>","PeriodicalId":21137,"journal":{"name":"Reproductive toxicology","volume":"136 ","pages":"Article 108960"},"PeriodicalIF":3.3,"publicationDate":"2025-05-30","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144195161","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":"Analyzing the impact of occupational exposures on male fertility indicators: A machine learning approach","authors":"Hamzeh Mohammadi ,&nbsp;Shayan Khoddam ,&nbsp;Farideh Golbabaei ,&nbsp;Somayeh Farhang Dehghan","doi":"10.1016/j.reprotox.2025.108959","DOIUrl":"10.1016/j.reprotox.2025.108959","url":null,"abstract":"<div><div>Occupational exposures are critical factors affecting workers' reproductive health. This study investigates the impact of magnetic fields, electric fields, whole-body vibration, noise levels, and heat stress on male reproductive indicators using advanced machine learning models. The aim is to identify key risk factors and provide predictive insights into workers' reproductive health over the next decade. Data were collected from 80 male workers in an automobile part manufacturing plant, capturing demographic characteristics, occupational exposures, biochemical markers, hormone levels, and sperm parameters. Five machine learning models logistic regression, bagging classifier, extreme gradient boosting, random forest, and support vector machine were trained and evaluated using 5-fold cross-validation to determine effective predictors of reproductive health outcomes. Exposure to whole-body vibration, magnetic fields, electric fields, and heat stress closely affected free testosterone levels, with SHAP importance indicating: Magnetic Field Exposure (0.339) and Wet Bulb Globe Temperature (0.138). Worker Age (0.244) was the most influential demographic factor negatively impacting Free Testosterone. The XGBoost and random forest achieved the highest AUC (0.99), outperforming other models in predictive accuracy. The Random Forest model Importance (% Increase in MSE) predicted that Electric Field Exposure (5 %) and Magnetic Field Exposure (4.7 %) would have the most substantial negative impact on Free Testosterone, followed by Worker Age (4.1 %). This study underscores the need for targeted interventions, such as improved workplace safety protocols and regular health monitoring, to protect workers’ reproductive health.</div></div>","PeriodicalId":21137,"journal":{"name":"Reproductive toxicology","volume":"136 ","pages":"Article 108959"},"PeriodicalIF":3.3,"publicationDate":"2025-05-29","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144192156","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":"Dye intermediates N-phenyl-2-naphthylamine and o-tolidine are novel environmental androgens with reproductive toxicity in male rats","authors":"Zhiheng Shangguan ,&nbsp;Kaiqiang Yang ,&nbsp;Qi Pan ,&nbsp;Hongli Hu ,&nbsp;Pan Wang","doi":"10.1016/j.reprotox.2025.108955","DOIUrl":"10.1016/j.reprotox.2025.108955","url":null,"abstract":"<div><div>Endocrine disruptors are environmental chemicals that can interfere with the endocrine system. However, research on endocrine disruptors that interfere with androgen action is still limited. In this study, two new environmental androgens were identified. N-Phenyl-2-naphthylamine (PNA) and o-tolidine are dye intermediates widely used in industry to produce organic pigments. We found that both PNA and o-tolidine activated androgen receptor (AR) transcriptional activity in the luciferase reporter assay and bound to AR-ligand binding domain directly in the surface plasmon resonance analysis. <em>In vivo</em> studies showed that PNA and o-tolidine induced the proliferation of seminal vesicle cells and increased seminal vesicle weight in immature male rats, indicating that these two compounds had androgenic activity <em>in vivo</em>. In addition, in mature male rats, PNA and o-tolidine reduced sperm concentration and motility and increased sperm deformities, and caused atrophy of the seminiferous tubules of the testis and decreased testosterone levels. These results suggest that PNA and o-tolidine are novel environmental androgens, which bind and activate AR and have toxicological effects on male reproductive function.</div></div>","PeriodicalId":21137,"journal":{"name":"Reproductive toxicology","volume":"136 ","pages":"Article 108955"},"PeriodicalIF":3.3,"publicationDate":"2025-05-29","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144189405","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}