Reproductive toxicology最新文献

{"title":"Developmental exposure to an environmentally relevant dose of Bisphenol S impairs postnatal growth and disrupts placental transcriptional profile in female rat","authors":"J. Fudvoye ,&nbsp;D. Lopez-Rodriguez ,&nbsp;C. Glachet ,&nbsp;D. Franssen ,&nbsp;Q. Terwagne ,&nbsp;A. Lavergne ,&nbsp;A.F. Donneau ,&nbsp;C. Munaut ,&nbsp;P. Dehan ,&nbsp;A. Lomniczi ,&nbsp;A.S. Parent","doi":"10.1016/j.reprotox.2025.108854","DOIUrl":"10.1016/j.reprotox.2025.108854","url":null,"abstract":"<div><div>Because of its possible adverse effects on human health and its ubiquitous nature, Bisphenol A (BPA) is gradually being replaced by presumably safer alternatives like Bisphenol S (BPS). However, data regarding the effects of developmental exposure to BPS on pregnancy and fetal outcomes are very scarce. Here we show that perinatal exposure to BPS at a very low dose significantly impairs postnatal growth and affects the placental transcriptome in rats. Oral exposure one week before mating and during gestation and lactation to a very low dose of BPS (25 ng/kg/day) is associated with impaired postnatal growth without significant difference in fetal weight on gestational day 18 in females. In contrast, in males, exposure to BPS 25 decreased fetal weight on gestational day 18 but growth restriction did not persist into adulthood. In female, exposure to this very low dose of BPS decreased the placental mRNA expression of fucosyltransferase2 (<em>Fut2</em>), pregnancy-specific glycoprotein 22 (<em>Psg22</em>), Wnt family member 7b (<em>Wnt7b</em>) which are involved in early placental development. Placental DNA methylation of steroid receptor coactivator 2 (<em>src2</em>), a key mediator of steroid induced decidualization, was significantly reduced, while placental <em>src2</em> mRNA expression was unaffected. These results suggest that early exposure to a very low dose of BPS has long term consequences on growth trajectory and is associated with placental dysregulation.</div></div>","PeriodicalId":21137,"journal":{"name":"Reproductive toxicology","volume":"132 ","pages":"Article 108854"},"PeriodicalIF":3.3,"publicationDate":"2025-02-09","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143394676","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 sub-chronic exposure to Kalach on male reproductive system and sperm function: In silico modelling and in vivo study in rats","authors":"Marwa Ben Amor ,&nbsp;Latifa Hamdaoui ,&nbsp;Salima Daoud ,&nbsp;Mariem Ammar ,&nbsp;Nour Louati ,&nbsp;Aida Elleuch ,&nbsp;Riadh Badraoui ,&nbsp;Lobna Ben Mahmoud ,&nbsp;Ikram Ben Amor ,&nbsp;Afifa Sellami ,&nbsp;Tarek Rebai","doi":"10.1016/j.reprotox.2025.108853","DOIUrl":"10.1016/j.reprotox.2025.108853","url":null,"abstract":"<div><div>Kalach 360 SL (KL), a glyphosate-based herbicide, is among the most widely used herbicides in Tunisia. This study aimed to evaluate the impact of sub-chronic exposure to KL on the male reproductive system and sperm parameters in adult rats after one and two cycles of spermatogenesis. 15 rats were randomly divided into three groups: a control group (G1) and two experimental groups (G2 and G3), exposed to KL at a dose of 102.2 mg/kg each day for 48 days. Treated groups G2 and G3 were sacrificed at day 48 and at day 96, respectively. We measured serum levels of testosterone and oestradiol, oxidative stress markers in testis, epididymal sperm parameters, sperm mitochondrial membrane potential (MMP), as well as testicular histopathology and morphometry as diagnostic markers of reproductive dysfunction. Additionally, we complemented the in vivo study with in silico modelling. Kl impaired sperm parameters, altered MMP, promoted oxidative stress, and affected testicular morphology, leading to reduced seminiferous epithelium height and delayed spermatogenesis arrest. KL caused significant declines in serum testosterone levels after 48 days (G2 group), supporting the herbicide's anti-androgenic activity. Notably, following cessation of exposure, testosterone levels increased and sperm concentration returned to normal by day 96 (G3 group). The computational approach revealed that glyphosate binds to the androgen receptor (2Q7K and 3QKM) with good affinities and strong molecular interactions, corroborating the in vivo results. We conclude that KL may interfere with spermatogenesis, impair male fertility, and function as a potential endocrine disruptor with anti-androgenic activity.</div></div>","PeriodicalId":21137,"journal":{"name":"Reproductive toxicology","volume":"132 ","pages":"Article 108853"},"PeriodicalIF":3.3,"publicationDate":"2025-02-06","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143374615","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":"Small extracellular vesicles derived from Nrf2-stimulated bone marrow mesenchymal stem cells ameliorated the testis damage and fertility disorder in doxorubicin-treated mice","authors":"Maryam Taher,&nbsp;Hanieh Jalali,&nbsp;Homa Mohseni Kouchesfehani","doi":"10.1016/j.reprotox.2025.108847","DOIUrl":"10.1016/j.reprotox.2025.108847","url":null,"abstract":"<div><div>Bone marrow mesenchymal/stromal stem cell (BMSC)-derived small extracellular vesicles (sEVs) are promising therapeutic agents owing to their low immunogenicity and ability to cross biological barriers. Doxorubicin (DOX), a common chemotherapeutic agent, damages testicular tissue. This study aimed to enhance the antioxidant activity of sEVs by activating the <em>Nrf2</em> gene in BMSCs and evaluate their therapeutic potential for DOX-induced fertility disorders. Testicular damage was induced by DOX in NMRI mice. BMSCs from Wistar rats were treated with Bardoxolone methyl (BaMet) to upregulate <em>Nrf2</em>. The sEVs were isolated through differential ultracentrifugation and validated for size, morphology, and protein expression. The antioxidant activity was assessed using specific kits. sEVs containing 10 μg of proteins were injected intravenously into DOX-injured mice. After 35 days, the testes were collected for histopathological, hormonal, and immunological analyses, along with the evaluation of sperm parameters. Male and female mice were paired to determine the pregnancy rates. BaMet-sEVs exhibited higher antioxidant activity and significantly improved serum testosterone levels, testicular cell populations, sperm viability, and motility in DOX-injured mice. In addition, BaMet-sEVs treatment enhanced fertility and increased the number of offspring. This study demonstrated the effectiveness of BaMet-sEVs in mitigating DOX-induced testicular damage.</div></div>","PeriodicalId":21137,"journal":{"name":"Reproductive toxicology","volume":"132 ","pages":"Article 108847"},"PeriodicalIF":3.3,"publicationDate":"2025-02-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143081070","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":"Single- and combined-heavy metals/metalloids exposures are associated with infertility in US women aged 20–44: NHANES 2013–2020 analysis","authors":"He-Bin Chi ,&nbsp;Jia-Jia Tang ,&nbsp;Xiao-Yuan Fan ,&nbsp;Han-Wen Zhang ,&nbsp;Feng Tang ,&nbsp;Xian-Shu Lin ,&nbsp;Bing-Rui Yang ,&nbsp;Na Li ,&nbsp;Jun Guo ,&nbsp;Li-An-Sheng Wu ,&nbsp;Qiu-Qi Huang ,&nbsp;Yin-Yin Xia","doi":"10.1016/j.reprotox.2025.108851","DOIUrl":"10.1016/j.reprotox.2025.108851","url":null,"abstract":"<div><div>Infertility is a major medical and social issue, with environmental factors, including metal exposure, playing a crucial role. This study analyzes how individual metals and their mixtures, which include a selection of heavy metals and metalloids totaling sixteen metals, contribute to infertility risk, using data from the National Health and Nutrition Examination Surveys. The study included 1326 women aged 20–44 years, comprising 1145 classified as fertile and 181 as infertile, with data on reproductive questionnaires and covariates. Infertility was defined through self-reported data. To assess the associations between exposure to these elements and infertility risk, we employed logistic regression, principal component analysis (PCA), restricted cubic splines (RCS), quantile regression with group-specific combination (qgcomp), and bayesian kernel machine regression (BKMR). After adjusting for potential confounders, logistic regression revealed positive associations of blood manganese (BMn) and urinary tin (USn) with infertility, whereas serum selenium (SSe) was negatively associated. RCS analysis demonstrated nonlinear relationships between urinary barium (UBa), urinary molybdenum (UMo), and urinary antimony (USb) and infertility. Potential interactions were identified between the following metal pairs: UMo and urinary cadmium, USb and UBa, and USb and UMo. PCA identified a positive association between PC3 and infertility (OR = 1.17, 95 % CI: 1.00, 1.36). The qgcomp model also indicated a positive association between metal mixtures and female infertility (OR = 1.25, 95 % CI: 1.03, 1.52). In conclusion, this study highlights significant associations between exposure to specific metals and infertility risk among women of reproductive age.</div></div>","PeriodicalId":21137,"journal":{"name":"Reproductive toxicology","volume":"132 ","pages":"Article 108851"},"PeriodicalIF":3.3,"publicationDate":"2025-02-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143123502","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 impact of air pollution on sperm DNA methylation","authors":"Jordan L. Moore ,&nbsp;Seth J. Parks ,&nbsp;Emma R. James ,&nbsp;Kenneth I. Aston ,&nbsp;Timothy G. Jenkins","doi":"10.1016/j.reprotox.2025.108850","DOIUrl":"10.1016/j.reprotox.2025.108850","url":null,"abstract":"<div><div>A number of environmental factors have been shown to impact the sperm epigenome. Air pollution is one of the largest health and environmental hazards in the world today and has been implicated in many modern diseases. Recently, air pollution has been shown to alter methylation signatures in some body tissues, indicating that air pollution may also affect the sperm epigenome. The present experiment was conducted to analyze how seasonal air pollution in the Salt Lake Valley may impact DNA methylation patterns in sperm and to establish a relationship between air pollution and sperm epigenetic health as measured by DNA methylation. Sperm DNA methylation patterns were assessed in 74 individuals, who presented at the University of Utah Andrology Clinic for semen analysis, using the Illumina Human MethylationEPIC BeadChip array. Each semen sample collected, as per the fifth edition of WHO reference values for human semen characterization, was deemed normal. Two sample groups from the Salt Lake Valley, Urban Winter (UW, n = 20), Urban Summer (US, n = 21), and two sample groups east of the Wasatch mountains, Rural Winter (RW, n = 19) and Rural Summer (RS, n = 14), were compared to assess the effect of air pollution on sperm DNA methylation patterns. Due to seasonal inversions, urban winters are characterized by increased air pollution compared to summer months. Therefore, the UW sample group was designated as treatment and the three remaining groups (US, RW, RS) were designated as control. We conducted multiple differential methylation analyses using a sliding window approach which utilized the USeq software package. A sliding window analysis of UW versus US was conducted first, followed by a confirmatory analysis comparing UW versus RW and RS. Outputs from the USeq analysis were assessed using several tools including the Stanford GREAT analysis and an analysis of methylation instability at key promoter regions in sperm. The sliding window analysis identified six differentially methylated regions (DMRs) between the UW and US groups (Wilcoxon FDR ≥ 40, corresponding p-value of ∼0.0001). Three of these six regions were confirmed with the second confirmatory analysis of UW versus RS/RW (Wilcoxon FDR ≥ 20, p-value&lt;0.01). According to a GREAT analysis, each of the identified regions exhibited multiple gene ontology associations. Air pollution subtly alters DNA methylation in sperm, indicating that certain regions of the sperm epigenome may be susceptible to air pollution-induced modification with possible implications for reproductive and offspring health.</div></div>","PeriodicalId":21137,"journal":{"name":"Reproductive toxicology","volume":"132 ","pages":"Article 108850"},"PeriodicalIF":3.3,"publicationDate":"2025-02-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143081072","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":"Teratogenic effect evaluation of Monascus red oral exposure to pregnant rats and their gut microbiota","authors":"Yuenan Wang ,&nbsp;Xuedan Xu ,&nbsp;Yun Liu ,&nbsp;Zhenfeng Huang ,&nbsp;Hongxia Wang ,&nbsp;Kexin Wang ,&nbsp;Yayi Huang ,&nbsp;Xinyu Yang ,&nbsp;Tingting Sun ,&nbsp;Jieling Wang ,&nbsp;Jianbin Tan ,&nbsp;Xingfen Yang ,&nbsp;Min Zhao","doi":"10.1016/j.reprotox.2025.108843","DOIUrl":"10.1016/j.reprotox.2025.108843","url":null,"abstract":"<div><div><em>Monascus</em> red (MR) is widely used as a natural food colorant and preservative in East Asia. However, the potential effects of MR during pregnancy remains unknown. In this study, MR was administrated to Sprague-Dawley (SD) rats at doses of 0, 0.50, 1.58, and 5.00 g/kg bw on gestational days 6–15 by oral gavage. In the maternal and embryo-fetal examinations, there were no marked toxicities in terms of general clinical signs, body weight, food consumption, serum endocrine indices, organ weights, thyroid histopathology, examinations of uterine contents and fetuses. In the gut microbiota analysis, the 5.00 g/kg bw dose of MR decreased the α diversity and slightly changed their community structure at the genus level. Yet no marked toxicities in maternal animals or embryo-fetal development were observed. The no-observed-adverse-effect-level (NOAEL) of the maternal and developmental toxicity through oral exposure to MR was 5.00 g/kg bw, the highest dose tested in rats.</div></div>","PeriodicalId":21137,"journal":{"name":"Reproductive toxicology","volume":"132 ","pages":"Article 108843"},"PeriodicalIF":3.3,"publicationDate":"2025-02-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143123504","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Gestational triclosan exposure and its effects on childneurodevelopment – A systematic review","authors":"Aleksander Brandão Santana ,&nbsp;Lídia EmmanuelaWiazowski Spelta ,&nbsp;Joselin Valeska Martinez-Sobalvarro ,&nbsp;Raphael Caio Tamborelli Garcia ,&nbsp;Tiago Marques dos Reis ,&nbsp;Larissa Helena Lobo Torres","doi":"10.1016/j.reprotox.2025.108849","DOIUrl":"10.1016/j.reprotox.2025.108849","url":null,"abstract":"<div><div>Triclosan (TCS) is a lipophilic antimicrobial agent present in commercial and healthcare products. Despite its beneficial properties, TCS disrupts thyroid hormone homeostasis and may be linked to metabolic disorders, cardiotoxicity, and increased cancer risk. Evidence on prenatal TCS exposure and adverse neurobehavioral outcomes is limited. This systematic review aimed to verify whether prenatal exposure to TCS is associated with neurobehavioral impairments. Observational studies with pregnant women exposed to TCS during pregnancy were included. The MEDLINE, EMBASE, Scopus, Web of Science, and LILACS databases were searched for studies up to February 27, 2024. Titles and abstracts were first screened, followed by full-text readings by two independent reviewers. Data extraction was performed independently, with conflicts resolved by consensus with a third reviewer. The included studies were assessed using an adapted Downs and Black tool and qualitatively synthesized. Certainty of evidence was assessed by GRADE. The study protocol was registered with PROSPERO (CRD42024526426). Among 17 studies, 14 cohort studies met the inclusion criteria. The sample size ranged from 193 to 794 pairs of pregnant women and children. Exposure to TCS throughout pregnancy resulted in median concentrations from 0.40 ng/mL to 28.2 ng/mL. Four studies suggested a potential association between prenatal TCS exposure and neurodevelopmental deficits, such as externalizing problems, attention issues, hyperactivity, somatization, emotional symptoms, social awareness, and communication; in contrast, eight studies found no significant effect. The studies had low certainty of evidence. Considering the heterogeneity and confounding factors, further investigation is required to confirm that prenatal TCS exposure leads to neurobehavioral disorders.</div></div>","PeriodicalId":21137,"journal":{"name":"Reproductive toxicology","volume":"132 ","pages":"Article 108849"},"PeriodicalIF":3.3,"publicationDate":"2025-01-30","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143074996","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":"Cypermethrin triggers oxidative stress, apoptosis, and inflammation in bovine mammary glands by disruption of mitogen-activated protein kinase (MAPK) pathways and calcium homeostasis","authors":"Junhun Kweon ,&nbsp;Whasun Lim ,&nbsp;Hojun Lee ,&nbsp;Jinyoung Kim ,&nbsp;Gwonhwa Song ,&nbsp;Wooyoung Jeong ,&nbsp;Jiyeon Ham","doi":"10.1016/j.reprotox.2025.108842","DOIUrl":"10.1016/j.reprotox.2025.108842","url":null,"abstract":"<div><div>Cyano-(3-phenoxyphenyl)methyl]3-(2,2-dichloroethenyl)-2,2-dimethylcyclopropane-1-carboxylate (cypermethrin) is a pyrethroid insecticide that is widely used to repel insects, such as cockroaches and ants. In addition to the target insects, its hazards have been outlined for carp; mice; and the nervous, reproductive, and gastrointestinal systems of humans. However, the effects of cypermethrin on the mammary tissue and milk production in dairy cattle remain unknown. Therefore, in the present study, we aimed to elucidate the impact of cypermethrin on dairy cattle using bovine mammary epithelial cells (MAC-T), which play key roles in milk yield and quality maintenance. First, we assessed the effects of cypermethrin on cell viability, proliferation, and cell cycle progression, followed by correlated gene expression analysis. Cypermethrin-treated cells exhibited G₁ phase arrest and an increase in the sub G₁ population. The population of MAC-T cells in both early and late apoptotic phases was increased following cypermethrin exposure. Moreover, cypermethrin caused mitochondrial calcium overload and diminished the mitochondrial membrane potential in MAC-T cells. We also observed the disruption of mitogen-activated protein kinase (MAPK) cascades and eventually, apoptotic cell death and excessive oxidative stress in cypermethrin-exposed MAC-T cells. In addition, cypermethrin affects the transcription levels related to apoptosis and inflammation, which may lead to the development of clinical morbidities, such as mastitis.</div></div>","PeriodicalId":21137,"journal":{"name":"Reproductive toxicology","volume":"132 ","pages":"Article 108842"},"PeriodicalIF":3.3,"publicationDate":"2025-01-28","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143067561","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":"Association between menopausal age and smoking status defined using urinary cotinine or tobacco-specific nitrosamine metabolite 4-(methylnitrosamino)-1-(3-pyridyl)-1-butanol: The Korea National Health and Nutrition Examination Survey 2016–2018","authors":"Yunjeong Park ,&nbsp;Hyemin Park ,&nbsp;Inha Lee ,&nbsp;Jae Hoon Lee ,&nbsp;SiHyun Cho ,&nbsp;Young Sik Choi","doi":"10.1016/j.reprotox.2025.108846","DOIUrl":"10.1016/j.reprotox.2025.108846","url":null,"abstract":"<div><div>This study aimed to establish the optimal cut-off values for urinary cotinine and 4-(methylnitrosamino)-1-(3-pyridyl)-1-butanol (NNAL)to determine smoking status in Korean women over 20 years of age and to assess the correlation of these biomarkers with reproductive health, particularly menopausal age, in postmenopausal women. Utilizing data from the 7th edition of the Korea National Health and Nutrition Examination Survey (2016–2018), researchers included postmenopausal women aged 40–60 years who were within 5 years of menopause. Self-reported smoking status was aligned with biomarkers levels to calculate optimal cut-off values, classifying a total of 503 postmenopausal women into four groups: never smokers (cotinine &lt;0.738 ng/mL, NNAL &lt;1.595 pg/mL), secondhand smokers (SHSrs; cotinine 0.738–37.7 ng/mL, NNAL 1.595–12.35 pg/mL), light current smokers (cotinine 37.7–837 ng/mL, NNAL 12.35–91.55 pg/mg), and heavy current smokers (cotinine &gt;837 ng/mL, NNAL &gt;91.55 pg/mL). Differences in menopausal age were analyzed using Kaplan–Meier curves and log-rank tests. The results indicated significant differences in menopausal age between never smokers and heavy smokers (51.4 ± 3.9 vs. 49.6 ± 3.0 years, p = 0.001) as well as SHSrs and heavy smokers (51.4 ± 3.3 vs. 49.6 ± 3.0 years, p = 0.001) when applying urinary cotinine cutoff values. However, no significant differences in menopausal age were observed based on NNAL cutoffs. These findings suggest urinary cotinine levels correlated more strongly with menopausal age than using urine NNAL levels for defining smoking status among postmenopausal Korean women. Heavy current smokers, as identified by urinary cotinine levels, experienced menopause at an earlier age compared to never smokers and SHSrs.</div></div>","PeriodicalId":21137,"journal":{"name":"Reproductive toxicology","volume":"132 ","pages":"Article 108846"},"PeriodicalIF":3.3,"publicationDate":"2025-01-28","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143067557","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":"Chronic unpredictable stress exposure disrupts testicular function by modulating germ cell-junctional dynamics and Nrf2/HO-1/IKKβ/NF-κB pathway","authors":"Shubhanshu Yadav,&nbsp;Anupam Yadav,&nbsp;Raghav Kumar Mishra","doi":"10.1016/j.reprotox.2025.108845","DOIUrl":"10.1016/j.reprotox.2025.108845","url":null,"abstract":"<div><div>The unpredictable nature of stress complicates understanding its relationship with male infertility. In this study, we investigated testicular germ cell and junctional dynamics in male mice following exposure to chronic unpredictable stress (CUS). Adult Parkes male mice were exposed to CUS for 35 days (one complete spermatogenic cycle), with a random stressor (restraint stress, water deprivation, food deprivation, light flashing, wet bedding, cage shaking, or cage tilting) applied once per day in an intermittent and unpredictable manner to avoid repeating the same stimulus on consecutive days. CUS exposure caused behavioral alterations in mice, as observed through the forced swim test and the tail suspension test. CUS inhibited testosterone biosynthesis by decreasing steroidogenic markers (SF-1, StAR, 3β-HSD, and 17β-HSD). It also resulted in altered oxido-inflammatory and apoptotic markers, including increased LPO, Caspase-3, IKKβ, and NF-κB, along with decreased Nrf2, HO-1, SOD, and catalase in the testis. CUS exposure reduced 1 C and 4 C germ cell populations and decreased germ cell ratios (1 C:2 C, 4 C:2 C, and 4 C:S-phase), impairing sperm development. CUS disrupted meiosis initiation, chromosomal synapsis, and germ cell maintenance by reducing Stra8, SYCP3, and Piwil1 expression in the testis. It also adversely affected blood-testis barrier markers, such as ZO-1 and connexin43. These changes led to altered testicular histomorphology, reduced daily sperm production, and disrupted germ cell dynamics. The findings suggest that CUS inhibits steroidogenesis and perturbs the Nrf2/HO-1/IKKβ/NF-κB oxido-inflammatory pathway. This leads to disrupted germ cell dynamics, compromised blood-testis barrier integrity, altered histomorphology, and reduced sperm production, collectively resulting in testicular dysfunction.</div></div>","PeriodicalId":21137,"journal":{"name":"Reproductive toxicology","volume":"132 ","pages":"Article 108845"},"PeriodicalIF":3.3,"publicationDate":"2025-01-28","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143067560","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}