Reproductive toxicology最新文献

{"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}

{"title":"Investigation of potential toxic effects of nano- and microplastics on human endometrial stromal cells","authors":"Nara Kim ,&nbsp;Jae Hoon Lee ,&nbsp;Inha Lee ,&nbsp;Joo Hyun Park ,&nbsp;Gee Soo Jung ,&nbsp;Min Jung Lee ,&nbsp;Wooseok Im ,&nbsp;SiHyun Cho ,&nbsp;Young Sik Choi","doi":"10.1016/j.reprotox.2025.108848","DOIUrl":"10.1016/j.reprotox.2025.108848","url":null,"abstract":"<div><div>Nanoplastics (NPs) and microplastics (MPs) have become a global concern in recent years. Most current research on the impact of plastics on obstetrics has focused on their accumulation in specific tissues in animal models and the disease-causing potential of MPs. However, there is a relative lack of research on the cellular changes caused by the accumulation of MPs.</div><div>In this study, we aimed to establish a proper in vitro exposure protocol for polystyrene (PS)-NPs and MPs and to investigate possible cytotoxic effects of PS-NPs and MPs on human endometrial stromal cells (ESCs) using different plastic sizes and concentrations. The results showed that smaller plastics, specifically 100 nm PS-NPs and 1 μm PS-MPs, had a higher cellular uptake propensity than larger particles, such as 5 μm PS-MPs, with significant morphological changes and cell death observed at concentrations above 100 μg/mL a 24-h period. In addition, confocal microscopy and real-time imaging confirmed the accumulation of these particles in the nucleus and cytoplasm, with internalization rates correlating with particle size. Also, 100 nm PS-NPs reduced cell proliferation and induced apoptosis. In conclusion, this study demonstrates that exposure to 100 nm PS-NPs and 1 μm PS-MPs leads to dynamic accumulation in ESCs, resulting in cell death or decreased proliferation at specific concentrations, which highlights the potential cellular toxicity of NPs or MPs.</div></div>","PeriodicalId":21137,"journal":{"name":"Reproductive toxicology","volume":"132 ","pages":"Article 108848"},"PeriodicalIF":3.3,"publicationDate":"2025-01-28","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143067588","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":"Investigations on the effects of in vitro exposure of mouse ovaries to withaferin A, a new candidate for chemotherapy","authors":"Gaby Judith Quispe Palomino ,&nbsp;Rensson Homero Céliz Ygnacio ,&nbsp;Laritza Ferreira de Lima ,&nbsp;Alesandro Silva Ferreira ,&nbsp;João Elmo da Cunha Neto ,&nbsp;Gildas Mbemya Tetaping ,&nbsp;Francisco Denilson Rodrigues Gomes ,&nbsp;Otilia Deusdênia Loiola Pessoa ,&nbsp;Ramon da Silva Raposo ,&nbsp;Danilo Damasceno Rocha ,&nbsp;Cláudia do Ó Pessoa ,&nbsp;José Ricardo Figueiredo ,&nbsp;Naiza Arcângela Ribeiro de Sá ,&nbsp;Ana Paula Ribeiro Rodrigues","doi":"10.1016/j.reprotox.2025.108844","DOIUrl":"10.1016/j.reprotox.2025.108844","url":null,"abstract":"<div><div>This study aimed to investigate, <em>in vitro</em>, the toxicity of WTA on ovarian follicles. Initially, a cytotoxicity assay was conducted using tumor and non-tumor cell lines to determine the IC. Initially, a cytotoxicity assay was conducted using tumor and non-tumor cell lines to determine the IC₅₀ of the WTA and validate its antitumor activity. Mouse ovaries were cultured <em>in vitro</em> (IVC) for 6 days in the presence of 1 % dimethyl sulfoxide (DMSO), doxorubicin at 0.3 µg/mL (DXR), or WTA at 0.6 µM or 6.0 µM. DXR or WTA were added to the IVC medium once (₁DXR, ₁WTA0.6, ₁WTA6.0) or three times (₃DXR, ₃WTA0.6, ₃WTA6.0). After the IVC, the ovarian stroma, follicular morphology and development, cell proliferation, senescence, DNA damage, and apoptosis were assessed. The degeneration rate in ₃DXR and WTA6.0 (1x and 3x) was higher (p &lt; 0.05) compared to the DMSO group. ₁DXR and ₃WTA0.6 reduced (p &lt; 0.05) the percentage of primordial follicles and increased (p &lt; 0.05) the number of developing follicles compared to the control (CTR) and DMSO groups. An increase (p &lt; 0.05) in lipofuscin granules was observed with DXR and WTA at both concentrations and exposure frequencies compared to the CTR. In the presence of ₃WTA0.6, staining for cleaved caspase-3 was more pronounced (p &lt; 0.05). Additionally, ₃WTA0.6, ₁WTA6.0, and ₃DXR increased (p &lt; 0.05) DNA fragmentation in the stroma compared to the CTR and DMSO groups. We conclude that, like chemotherapy agents used for cancer treatment, WTA induces severe cytotoxic effects on ovarian follicles and stroma, especially at high concentrations and exposure frequencies.</div></div>","PeriodicalId":21137,"journal":{"name":"Reproductive toxicology","volume":"132 ","pages":"Article 108844"},"PeriodicalIF":3.3,"publicationDate":"2025-01-26","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143060398","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}