Reproductive toxicology最新文献

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Maternal high-fat diet programs reproductive function of female offspring rat through IL-6-mediated regulation of Kiss1 gene methylation 母体高脂肪饮食通过il -6介导的Kiss1基因甲基化调节雌性后代大鼠的生殖功能。
IF 3.3 4区 医学
Reproductive toxicology Pub Date : 2025-06-18 DOI: 10.1016/j.reprotox.2025.108975
Shanshan Zhao , Yihong Huang , Niankun Chen , Junling Zhou , Shaole Shi , Wei Chen , Lemin Yuan , Zilian Wang , Dongyu Wang
{"title":"Maternal high-fat diet programs reproductive function of female offspring rat through IL-6-mediated regulation of Kiss1 gene methylation","authors":"Shanshan Zhao ,&nbsp;Yihong Huang ,&nbsp;Niankun Chen ,&nbsp;Junling Zhou ,&nbsp;Shaole Shi ,&nbsp;Wei Chen ,&nbsp;Lemin Yuan ,&nbsp;Zilian Wang ,&nbsp;Dongyu Wang","doi":"10.1016/j.reprotox.2025.108975","DOIUrl":"10.1016/j.reprotox.2025.108975","url":null,"abstract":"<div><div>Maternal high-fat diet (HFD) is known to impair the reproductive function of female offspring, but the underlying epigenetic mechanisms of this developmental programming remain unclear. In this study, female rats were fed either a control diet (CD; 10 % kcal from fat) or an HFD (60 % kcal from fat) prior to and during gestation and lactation. After weaning, female offspring were randomly assigned to continue on either a CD or HFD, resulting in four groups: C/C, C/HF, HF/C, and HF/HF. Maternal HFD significantly reduced primordial follicle numbers, increased follicular atresia and granulosa cell apoptosis, and disrupted sex hormone levels in female offspring at 3 months of age. Female offspring from HFD-fed dams exhibited reduced <em>Kiss1</em> gene expression and increased promoter methylation in both the ovaries and hypothalami. Additionally, the IL-6/STAT3 pathway was activated, and the expression of Ten-eleven translocation methylcytosine dioxygenase 2 (TET2), a key regulator of DNA demethylation, was downregulated. Post-weaning exposure to a normal diet partially attenuated these effects by 6 months of age. Furthermore, in vitro experiments demonstrated that IL-6/STAT3 signaling downregulated the expression of TET2 and Kisspeptin. Overall, our study demonstrates that maternal HFD consumption reduces TET2 expression in the ovaries and hypothalami of female offspring via the IL-6/STAT3 pathway, leading to <em>Kiss1</em> promoter hypermethylation and a subsequent decrease in Kisspeptin levels. These findings highlight a potential epigenetic mechanism linking maternal diet to long-term reproductive toxicity in female offspring.</div></div>","PeriodicalId":21137,"journal":{"name":"Reproductive toxicology","volume":"136 ","pages":"Article 108975"},"PeriodicalIF":3.3,"publicationDate":"2025-06-18","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144336904","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}
引用次数: 0
DEHP and its metabolite MEHP exposure impairs endometrial decidualization during early pregnancy via up-regulation of Mtmr6 DEHP及其代谢物MEHP暴露通过上调Mtmr6损害妊娠早期子宫内膜去个体化。
IF 3.3 4区 医学
Reproductive toxicology Pub Date : 2025-06-18 DOI: 10.1016/j.reprotox.2025.108976
Li-Ping Tan , Liu Yuan , Yan Zhang , Jun-Lin He , Xin Yin , Yi-Dan Ma , Xue-Mei Chen , Wei-Ke Li , Fang-Fang Li , Ru-Fei Gao
{"title":"DEHP and its metabolite MEHP exposure impairs endometrial decidualization during early pregnancy via up-regulation of Mtmr6","authors":"Li-Ping Tan ,&nbsp;Liu Yuan ,&nbsp;Yan Zhang ,&nbsp;Jun-Lin He ,&nbsp;Xin Yin ,&nbsp;Yi-Dan Ma ,&nbsp;Xue-Mei Chen ,&nbsp;Wei-Ke Li ,&nbsp;Fang-Fang Li ,&nbsp;Ru-Fei Gao","doi":"10.1016/j.reprotox.2025.108976","DOIUrl":"10.1016/j.reprotox.2025.108976","url":null,"abstract":"<div><div>DEHP is a pervasive endocrine disrupting chemical with multiple adverse effects on the female reproductive system. However, its impact on endometrial decidualization, the foundation for embryo implantation and successful pregnancy, remains poorly defined, and the underlying regulatory mechanisms have been rarely explored. In present study, we utilized several assays with DEHP-exposed mouse decidual tissues to clarify whether DEHP exposure confers adverse effects on decidualization. The results showed that 1000 mg/kg/d DEHP exposure led to a significant reduction in the weight and area of the uterine deciduoma, accompanied by a significant decrease in the expression of decidualization markers on GD6, GD8 of pregnancy, and PD8 of pseudopregnancy in mice. Moreover, the <em>in vitro</em> findings revealed that exposure to 12.5 μM MEHP, the primary and active metabolite of DEHP, disturbed the cytoskeletal remodeling and downregulated the marker molecules during endometrial stromal cell decidualization. Meanwhile, we detected that Mtmr6 as identified by proteomics analysis, was up-regulated after DEHP and MEHP exposure <em>in vivo</em> and <em>in vitro</em>. Knockdown of Mtmr6 alleviated the deficiencies in stromal cell decidualization induced by DEHP’ metabolite MEHP. Furthermore, we also found that the active-site residue ALA-131 of Mtmr6 may be the direct binding site for MEHP by performing molecular docking. This study uncovered the adverse effects of DEHP on endometrial decidualization and revealed the possible mechanisms, providing potential strategies for minimizing their toxicological effects on female reproductive health.</div></div>","PeriodicalId":21137,"journal":{"name":"Reproductive toxicology","volume":"136 ","pages":"Article 108976"},"PeriodicalIF":3.3,"publicationDate":"2025-06-18","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144336903","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}
引用次数: 0
In utero exposure to estrogenic bisphenol analogues increases mammary tissue stiffness 子宫内暴露于雌激素双酚类似物会增加乳腺组织硬度
IF 3.3 4区 医学
Reproductive toxicology Pub Date : 2025-06-11 DOI: 10.1016/j.reprotox.2025.108974
Jillian M. Poska , Clarissa Wormsbaecher , Brittney M. Cumbia , Madeline R. Price , Marcos Cortes-Medina , Jacob Holter , Shashwat Agarwal , Xiaokui Molly Mo , Jonathan W. Song , Craig J. Burd
{"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}
引用次数: 0
Impact of particulate matter 2.5 on placental ultrastructure including mitochondrial damage through oxidative stress 颗粒物质2.5对氧化应激引起的胎盘超微结构包括线粒体损伤的影响
IF 3.3 4区 医学
Reproductive toxicology Pub Date : 2025-06-10 DOI: 10.1016/j.reprotox.2025.108973
Gain Lee , Jung Mi Han , Young-Ah You , Yoon-Young Go , Sunwha Park , Young Min Hur , Soo Min Kim , Ki-Hwan Han , Young Ju Kim
{"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<sub>2.5</sub>) 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<sub>2.5</sub> 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<sub>2.5</sub> 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<sub>2.5</sub> 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}
引用次数: 0
Limited passage and functional effects of polystyrene micro- and nanoplastics in a physiologically-relevant in vitro human placental co-culture model 聚苯乙烯微塑料和纳米塑料在生理相关的体外人胎盘共培养模型中的有限传代和功能影响。
IF 3.3 4区 医学
Reproductive toxicology Pub Date : 2025-06-06 DOI: 10.1016/j.reprotox.2025.108956
Jeske van Boxel , Sandra M. Nijmeijer , Manuel T. Heinzelmann , Sebastian Rupp , Majorie B.M. van Duursen
{"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}
引用次数: 0
Glycine intervention can alleviate imidacloprid-induced spermatogenic damage in rats 甘氨酸干预可减轻吡虫啉致大鼠生精损伤。
IF 3.3 4区 医学
Reproductive toxicology Pub Date : 2025-06-03 DOI: 10.1016/j.reprotox.2025.108970
Zhihui Zhang , Weilong Cheng , Junsong Xiao , Yixuan Li , Guoping Zhao , Yanbo Wang
{"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}
引用次数: 0
The use of pregabalin in early pregnancy and major congenital malformations: A systematic review and meta-analysis 普瑞巴林在早期妊娠和重大先天性畸形中的应用:一项系统回顾和荟萃分析
IF 3.3 4区 医学
Reproductive toxicology Pub Date : 2025-06-03 DOI: 10.1016/j.reprotox.2025.108958
Marina Atzenhoffer, Audrey Peron, Cyndie Picot, Michel Cucherat, Judith Cottin
{"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 (I<sup>2</sup> = 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}
引用次数: 0
Associations between urinary phthalate metabolite mixtures, semen quality, and serum reproductive hormone levels in Japanese men seeking fertility treatment 在寻求生育治疗的日本男性中,尿邻苯二甲酸盐代谢物混合物、精液质量和血清生殖激素水平之间的关系。
IF 3.3 4区 医学
Reproductive toxicology Pub Date : 2025-06-01 DOI: 10.1016/j.reprotox.2025.108957
Yuki Mizuno , Kazumitsu Yamasaki , Masahiro Uchida , Teruaki Iwamoto , Shoko Konishi
{"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}
引用次数: 0
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 在人颗粒细胞模型中,暴露于邻苯二甲酸盐混合物对排卵期间前列腺素产生的抑制作用可通过补充cAMP类似物来规避。
IF 3.3 4区 医学
Reproductive toxicology Pub Date : 2025-05-31 DOI: 10.1016/j.reprotox.2025.108968
Patrick R. Hannon , Katie L. Land , Hong Xu , James W. Akin , Thomas E. Curry
{"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 PGE<sub>2</sub> and PGF<sub>2α</sub> 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 PGE<sub>2</sub> and PGF<sub>2α</sub> 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}
引用次数: 0
Use of serotonin reuptake inhibitors (SSRIs) and serotonin and norepinephrine reuptake inhibitors (SNRIs) during pregnancy: Effect on fetal growth and long-term reproductive outcomes 妊娠期间使用血清素再摄取抑制剂(SSRIs)和血清素和去甲肾上腺素再摄取抑制剂(SNRIs):对胎儿生长和长期生殖结局的影响
IF 3.3 4区 医学
Reproductive toxicology Pub Date : 2025-05-30 DOI: 10.1016/j.reprotox.2025.108960
Debarshi Sarkar , Souvik Mandal , Srinwanti Bandyopadhyay , Sayan Bose , Jyoti Parkash , Shio Kumar Singh
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