Reproductive toxicology最新文献

{"title":"Quaternary ammonium compound exposure causes infertility by altering endocrine signaling and gametogenesis","authors":"Zachary A. Kirkpatrick ,&nbsp;Vanessa E. Melin ,&nbsp;Terry C. Hrubec","doi":"10.1016/j.reprotox.2024.108817","DOIUrl":"10.1016/j.reprotox.2024.108817","url":null,"abstract":"<div><div>Quaternary ammonium compounds (QACs) are common substances utilized in cleaners, ophthalmic solutions, swimming pool treatments, cosmetics, and other consumer goods. Previous studies have shown that QAC exposure causes infertility in both male and female mice. Based on these studies, we hypothesized that oral QAC exposure negatively impacts male and female reproduction through changes in physiologic and endocrine mechanisms rather than direct toxicity to gametes. Endocrine disruption was assessed by evaluating luteinizing hormone (LH) and follicle stimulating hormone (FSH) concentrations in male and female mice exposed orally throughout gestation and lactation, and by changes in estrogen and progesterone in in orally exposed females throughout pregnancy. Sperm functionality and spermatogenesis were assessed by in vitro fertilization; while Sertoli cell homeostasis was evaluated by determining cellular metabolism, cell cycle progression and blood-testes barrier (BTB) permeability. QAC exposure decreased LH, and FSH concentrations in both males and females, and decreased progesterone and estrogen concentrations during pregnancy. QACs significantly decreased Sertoli cell metabolism at 0.0005 % ADBAC+DDAC well before disruption of the BTB at 0.01 %. Fertilization was not affected 24 h after exposure but was decreased after a 10 day rest period suggesting a disruption in spermatogenesis rather than direct toxicity to sperm. Lastly, QAC exposure altered Sertoli cell cycling with a G2/M cycle arrest. While the effect of QAC exposure on humans is unknown, implications from the in vivo and in vitro studies are concerning given the rise in infertility rates and increased reliance on assisted reproductive technologies along with ubiquitous exposure to QACs.</div></div>","PeriodicalId":21137,"journal":{"name":"Reproductive toxicology","volume":"132 ","pages":"Article 108817"},"PeriodicalIF":3.3,"publicationDate":"2024-12-07","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142801573","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":"Maternal exposure to fine particulate matter in the air and risk for fetal congenital heart defects: A case-control study","authors":"Zhao Li ,&nbsp;Di Wang ,&nbsp;Lei Jin ,&nbsp;Jie Zhang ,&nbsp;Tao Xue ,&nbsp;Lei Jin","doi":"10.1016/j.reprotox.2024.108816","DOIUrl":"10.1016/j.reprotox.2024.108816","url":null,"abstract":"<div><div>Prior research into the association between fine particulate matter (PM_2.5) exposure and the risk for fetal congenital heart defect (CHD) has yielded inconclusive and conflicting results. More epidemiologic evidence from different regions is necessary. A case-control study was conducted with 360 CHD cases and 3600 healthy newborns. Both the cases and the controls were registered by the mothers in the Prenatal Health Care System during the first trimester and gave birth at hospitals in the Tongzhou District of Beijing between 2013 and 2018. Information on PM_2.5 was obtained from satellite remote sensing monitoring data. We estimated average monthly PM_2.5 exposure for participants from 3 months before the last menstrual period through 6 months of gestational period. A logistic regression model was used to estimate odd ratio (OR) (95 % confidence interval, CI) for PM_2.5 exposure level and fetal risk for CHD. In our study, PM_2.5 concentrations before pregnancy and in the first trimester were not associated with CHD risk. In the second trimester, 2nd high quartile PM_2.5 group during the second month were associated with a lower CHD risk (adjusted OR(aOR)= 1.42, 95 % CI: 1.04–1.94) and highest quartile level group of PM_2.5 exposure in the third month were associated with a reduced risk for fetal CHD (aOR=0.70, 95 % CI: 0.51–0.97). After Bonferroni’s α correction, no comparisons were statistically significant. In conclusion, no associations were found between PM_2.5 exposure level and fetal risk for CHD in our study.</div></div>","PeriodicalId":21137,"journal":{"name":"Reproductive toxicology","volume":"132 ","pages":"Article 108816"},"PeriodicalIF":3.3,"publicationDate":"2024-12-03","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142787025","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":"Detection and quantification of microplastics in endometrial polyps and their role in polyp formation","authors":"Shilin He ,&nbsp;Yanling Zhang","doi":"10.1016/j.reprotox.2024.108757","DOIUrl":"10.1016/j.reprotox.2024.108757","url":null,"abstract":"<div><div>With the increasing use of plastics, microplastic (MPs) pollution has garnered significant attention in recent years. Endometrial polyps are prevalent gynecological conditions in women of childbearing age, which impair endometrial receptivity and contribute to female infertility. However, no studies have yet reported the exposure of endometrial polyps to MPs. This study employed pyrolysis-gas chromatography/mass spectrometry and laser direct infrared spectroscopy to detect and compare MPs between normal endometrium and endometrial polyps. Using Py-GC/MS, we identified three main MPs in 14 normal endometrial samples and 16 endometrial polyps. The average abundance of MPs in the endometrial polyp group was significantly higher than in the normal endometrium group. The respective average abundance of polyethylene (PE), polystyrene (PS), and polyvinyl chloride (PVC) in the polyp and normal endometrium groups was 13.66 ± 2.0 vs. 7.132 ± 0.78 μg/g (p = 0.0009), 94.81 ± 10.67 vs. 69.29 ± 6.93 μg/g, and 67.67 ± 11.02 vs. 56.35 ± 6.90 μg/g. LDIR analysis revealed 13 different types of MPs, with polymethylmethacrylate being the most prevalent. Moreover, we discovered that PS microspheres can promote the proliferation and migration of endometrial stromal cells through PI3K/AKT pathway, which may be a key factor in the formation of endometrial polyps. This study is the first to explore the presence of MPs in endometrial polyps, compare the differences in MPs content between normal endometrium and endometrial polyps, and clarify the potential connection between MPs exposure and the formation of endometrial polyps. Further research is required to explore additional potential insights.</div></div>","PeriodicalId":21137,"journal":{"name":"Reproductive toxicology","volume":"132 ","pages":"Article 108757"},"PeriodicalIF":3.3,"publicationDate":"2024-11-29","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142771775","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":"Prenatal developmental toxicity evaluation of higher olefins in Sprague-Dawley rats","authors":"Quan Shi ,&nbsp;Michael G. Penman ,&nbsp;Juan-Carlos Carrillo ,&nbsp;Jamie Dunn ,&nbsp;Hua Shen ,&nbsp;Sophie Jia ,&nbsp;An R. Van Rompay ,&nbsp;Fabienne Hubert ,&nbsp;Peter J. Boogaard","doi":"10.1016/j.reprotox.2024.108756","DOIUrl":"10.1016/j.reprotox.2024.108756","url":null,"abstract":"<div><div>Higher olefins (HO) are used primarily as intermediates in the production of other chemicals, such as polymers, fatty acids, plasticizer alcohols, surfactants, lubricants, amine oxides and detergent alcohols. The potential prenatal developmental toxicity of five HO (i.e. Hex-1-ene, Nonene, branched, Octadec-1-ene, and Hydrocarbons, C12–30, olefin-rich, ethylene polymn. by product) were evaluated in prenatal development toxicity studies (OECD TG 414 (2001)) in Sprague-Dawley rats as part of the regulatory requirements for REACH registration. In each study, the HO were administered by gavage at dose levels of 0, 100, 300 and 1000 mg/kg bw/day from Day 3 to Day 19 of gestation. Maternal food consumption, body weights, and clinical signs were monitored throughout gestation. The rats were sacrificed on Day 20 of gestation and examined for standard parameters of reproductive performance (number of corpora lutea, number of implantations, pre- and post-implantation loss, number of live- and dead fetuses, sex-ratio and the weight of the reproductive organs). The fetuses were weighed and examined for external, visceral, and skeletal variations and malformations. The results from these studies showed that none of the HO treated groups showed maternal or embryo–fetal toxicity. Although occasionally incidental skeletal and visceral malformations were observed with Hex-1-ene and Octadec-1-ene, these findings were found to be spontaneous, unrelated to treatment and not indicative for any disturbance of fetal development. In conclusion, the No-Observed-Adverse-Effect Level (NOAEL) for all tested HO was determined to be 1000 mg/kg bw/day, which is the highest dose level administered, for both maternal and developmental toxicity.</div></div>","PeriodicalId":21137,"journal":{"name":"Reproductive toxicology","volume":"132 ","pages":"Article 108756"},"PeriodicalIF":3.3,"publicationDate":"2024-11-29","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142771789","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":"Oxidative stress and energy metabolism in male reproductive damage from single and combined high-power microwave exposure at 1.5 and 4.3GHz","authors":"Yanyang Li ,&nbsp;Binwei Yao ,&nbsp;Junqi Men ,&nbsp;Yueyue Pang ,&nbsp;Jingchao Gao ,&nbsp;Yanxin Bai ,&nbsp;Hui Wang ,&nbsp;Jing Zhang ,&nbsp;Li Zhao ,&nbsp;Xinping Xu ,&nbsp;Ji Dong ,&nbsp;Congsheng Li ,&nbsp;Ruiyun Peng","doi":"10.1016/j.reprotox.2024.108759","DOIUrl":"10.1016/j.reprotox.2024.108759","url":null,"abstract":"<div><div>The effect of multi-frequency electromagnetic environments on male reproduction has attracted the medical community’s interest. Studies have investigated the effects and mechanisms of single-frequency microwave exposure on male reproduction, but comparative research on high-power microwave (HPM) composite and single exposure remains scarce. This study aimed to examine the effects and mechanisms of combined 1.5 GHz and 4.3 GHz microwave exposure on male reproduction. Male Wistar rats were exposed to 1.5 GHz (L-band) and 4.3 GHz (C-band) electromagnetic radiation for 15 minutes. The four groups were: sham, 10 mW/cm² L-band, 10 mW/cm² C-band, and 5 mW/cm² L-band and 5 mW/cm² C-band compound. Assessments were made on the pathological structures of testes, sperm viability, serum sex hormones, oxidative stress, and energy metabolism levels after radiation. Exposure to 1.5 GHz and 4.3 GHz microwaves individually resulted in testicular tissue damage and reduced sperm quality. There was little difference between the damage caused by HPM composite and single exposure. The exposed groups showed histological and ultrastructural changes, with reduced spermatozoa viability, motility parameters, and serum testosterone, luteinizing hormone, follicle-stimulating hormone, and serum inhibin-B on days 1 and 7 after exposure. These tended to recover partially by day 14. Adenosine triphosphate content and lactate dehydrogenase and succinate dehydrogenase activities in the exposed testicular tissue decreased, corresponding to decreased superoxide dismutase activity and increased malondialdehyde content. Both single and combined exposure to L- and C-band HPM affect the male reproductive system. Exposure to single and compound HPM shows no significant difference in risks, with oxidative stress and energy metabolism disturbances playing key roles.</div></div>","PeriodicalId":21137,"journal":{"name":"Reproductive toxicology","volume":"132 ","pages":"Article 108759"},"PeriodicalIF":3.3,"publicationDate":"2024-11-29","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142771764","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":"Evaluation of cytoprotective effects of cannabidiol on neuroinflammation and neurogenesis process in rat offsprings","authors":"Deniz Catakli ,&nbsp;Yalcin Erzurumlu ,&nbsp;Halil Asci ,&nbsp;Mehtap Savran ,&nbsp;Serdar Sezer","doi":"10.1016/j.reprotox.2024.108761","DOIUrl":"10.1016/j.reprotox.2024.108761","url":null,"abstract":"<div><div>Natural compounds include complex chemical compounds that exist in plants, animals and microbes. Due to their broad spectrum of pharmacological and biochemical actions, they have been widely used to treat multifactorial diseases, including cancer. In addition, their demonstrated neuroprotective properties strongly support their use in the treatment of neurological diseases. The present study investigated the effect of cannabidiol (CBD), which can easily cross the placental barrier and is known to have anti-inflammatory effects, on fetal neuroinflammation and neurogenesis in a systemic inflammation model during pregnancy. Herein, 12 weeks adult pregnant rats (<em>n = 30</em>) were randomly divided into 5 groups with 6 rats in each group as follows: Control, LPS (lipopolysaccharide, <em>i.p.</em>), LPS+CBD 5 mg/kg (<em>i.p.</em>), LPS+CBD10 mg/kg (<em>i.p.</em>) and LPS+CBD30 mg/kg (<em>i.p.</em>). After the injections, blood samples of rats were collected, fetuses and placentas were taken by hysterectomy. Histopathological analysis, immunohistochemical staining, ELISA and immunoblotting analysis were performed to investigate neuroinflammatory and neurogenesis parameters in fetal brain and placenta tissues. Our findings indicated that CBD administration importantly suppressed the inflammatory process in the rat fetal brain by decreasing interleukin-1beta (IL-1β) and tumor necrosis factor-alpha (TNF-α) levels and diminishing nuclear factor kappa B (NF-κB) activation. Moreover, CBD inhibited lipopolysaccharide (LPS)-induced increasing levels of neuroinflammation-associated proteins, including glial fibrillary acidic protein (GFAP), S100B and cAMP-response element binding protein (CREB). These results suggest that CBD usage in pregnancy with inflammation conditions may be an effective therapeutic option for preventing conditions that may cause neuroinflammation in the fetal brain and adversely affect neurogenesis.</div></div>","PeriodicalId":21137,"journal":{"name":"Reproductive toxicology","volume":"132 ","pages":"Article 108761"},"PeriodicalIF":3.3,"publicationDate":"2024-11-29","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142771475","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":"Acetaminophen overdose inhibits steroidogenic acute regulatory protein expression by reducing AKT-mediated SP1 expression in human granulosa-lutein cells","authors":"Jung-Chien Cheng ,&nbsp;Qian Zhang ,&nbsp;Lingling Zhang ,&nbsp;Beibei Bi ,&nbsp;Hailong Wang ,&nbsp;Lanlan Fang ,&nbsp;Hsun-Ming Chang ,&nbsp;Ying-Pu Sun","doi":"10.1016/j.reprotox.2024.108764","DOIUrl":"10.1016/j.reprotox.2024.108764","url":null,"abstract":"<div><div>Overdose of acetaminophen (APAP) has been shown to adversely affect the outcome of pregnancy. The steroidogenic acute regulatory protein (StAR) plays a pivotal role in steroidogenesis, but the impact of APAP on StAR expression in adult human ovarian granulosa cells remains elusive. Here, we demonstrate that APAP overdose leads to the downregulation of StAR expression in the human granulosa cell tumor cell line, KGN, and in the primary culture of human granulosa-lutein (hGL) cells. Treatment of overdose APAP inhibits the activation of the AKT signaling pathway and downregulates the expression of transcription factor SP1. Using a small molecule of AKT activator and SP1 overexpression approaches, we show that the suppressive effect of APAP on StAR expression is mediated through the inhibition of AKT-mediated upregulation of SP1 expression. This study contributes to a deeper understanding of the pharmacological actions of APAP and its impacts on female reproductive health.</div></div>","PeriodicalId":21137,"journal":{"name":"Reproductive toxicology","volume":"132 ","pages":"Article 108764"},"PeriodicalIF":3.3,"publicationDate":"2024-11-29","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142772000","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":"Prenatal high-sucrose diet affects pulmonary artery contractile functions via MT receptors","authors":"Xueqin Feng ,&nbsp;Hongwei Fu ,&nbsp;Xiao Sun ,&nbsp;Hua Shu ,&nbsp;Yongning Zhu ,&nbsp;Yanyan Bai ,&nbsp;Qinggui Ren ,&nbsp;Xinying Liu ,&nbsp;Meng Liu ,&nbsp;Fanyong Zhang ,&nbsp;Yanping Wang","doi":"10.1016/j.reprotox.2024.108760","DOIUrl":"10.1016/j.reprotox.2024.108760","url":null,"abstract":"<div><div>A high sucrose diet during pregnancy may generate profound effects on vascular diseases in offspring later in life. Pulmonary artery (PA) functions is closely related to pulmonary hypertension, but whether and how prenatal high-sucrose diet (HS) affect pulmonary vasoreactivity in adult offspring remains unknown. We investigated the alterations of PA reactivity in postnatal offspring exposed to prenatal HS. Pregnant Sprague-Dawley rats were fed either a tap water or 20 % high sucrose solution throughout pregnancy. Pulmonary arteries from adult offspring were isolated and tested for all experiments. Prenatal HS increased vascular wall thickness, resulted in swollen mitochondria, and altered myofilament distribution in vascular smooth muscle layers of PA. Notably, the offspring's PAs from HS group showed increased vasoconstriction, but reduced PKC function and expression, suggesting that the dysfunction was not primary linked to PKC signals. RNA-Seq analysis of PA revealed that the MT1R and MT2AR genes were significantly increased in the HS group, but their protein levels decreased. This suggests that MT receptors, rather than PKC signaling, are the key factors to influencing vascular contraction of PAs exposure to prenatal HS.</div></div>","PeriodicalId":21137,"journal":{"name":"Reproductive toxicology","volume":"132 ","pages":"Article 108760"},"PeriodicalIF":3.3,"publicationDate":"2024-11-28","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142746674","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":"Nicotinamide mononucleotide enhances the developmental potential of mouse early embryos exposed to perfluorooctanoic acid","authors":"Hanwen Zhang,&nbsp;Yu Li,&nbsp;Na Li,&nbsp;Yilong Miao,&nbsp;Shaochen Sun,&nbsp;Ling Gu,&nbsp;Bo Xiong","doi":"10.1016/j.reprotox.2024.108762","DOIUrl":"10.1016/j.reprotox.2024.108762","url":null,"abstract":"<div><div>Perfluorooctanoic acid (PFOA) exposure severely affects the health of animals and humans, including early embryonic development, but the effective approaches to improve the quality of embryos exposed to PFOA have not been explored. Here, we report that nicotinamide mononucleotide (NMN) can be used to attenuate the impairment of mouse early embryos caused by PFOA exposure. We find that NMN supplementation maintains the normal spindle assembly and proper chromosome alignment by restoring the acetylation level of microtubule to enhance the mitotic capacity of embryos at zygotic cleavage stage under PFOA exposure. In addition, NMN exerts its beneficial effect by enhancing mitochondrial function and eliminating accumulated reactive oxygen species (ROS), which in turn alleviates DNA damage and apoptosis in PFOA-exposed 2-cell embryos. Moreover, NMN ameliorates the quality of PFOA-exposed blastocysts <em>via</em> recovering the octamer-binding transcription factor 4 (Oct4) expression, the actin dynamics, and the total number of cells. Collectively, our findings demonstrate that supplementation with NMN is a feasible strategy to restore the compromised early embryonic development under PFOA exposure, providing a scientific basis for application of NMN to increase the female fertility.</div></div>","PeriodicalId":21137,"journal":{"name":"Reproductive toxicology","volume":"132 ","pages":"Article 108762"},"PeriodicalIF":3.3,"publicationDate":"2024-11-28","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142746004","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":"Multi-omics revealed activation of TNF-α induced apoptosis signaling pathway in testis of DEHP treated prepubertal male rat","authors":"Zishui Fang ,&nbsp;Zirun Jin ,&nbsp;Qiancheng Zhao ,&nbsp;Jiaming Weng ,&nbsp;Zhe Zhang ,&nbsp;Yuzhuo Yang ,&nbsp;Hui Jiang","doi":"10.1016/j.reprotox.2024.108758","DOIUrl":"10.1016/j.reprotox.2024.108758","url":null,"abstract":"<div><div>Di-(2-ethylhexyl) phthalate (DEHP) exposure has been associated with male reproductive damage, but the mechanisms involved remain incompletely defined. This study aims to investigate the effects of DEHP exposure on the testes of prepubertal rats through an integrative analysis of metabolomics and transcriptomics, combined with molecular experiments. DEHP exposure resulted in decreased testis weight and increased oxidative stress level in the testis tissues of prepubertal male rats. Moreover, our findings showed a disordered testis structure, reduced spermatogenic and Sertoli cells as well as destruction of mitochondria structure in the testis tissues of DEHP-treated prepubertal male rats. Transcriptome function analysis together with metabolome function analysis indicated that spermatogenesis, apoptosis, inflammatory, lipid metabolism as well as DNA repair signaling pathway were enriched in the testis of DEHP-treated prepubertal male rats. The integrative omics analysis further suggested that TNF-α induced apoptosis played a crucial role in mediating the detrimental effects of DEHP exposure on the testis of prepubertal rats, which was validated by ELISA, Western blotting and Tunel assays. Validation experiments conducted <em>in vitro</em> using GC-2 cells corroborated these findings, demonstrating that mono-(2-ethylhexyl) phthalate (MEHP), the main active metabolite of DEHP, significantly inhibits cell proliferation and increases apoptosis via activating the TNF-α apoptosis pathway. Overall, these findings provided a novel mechanism of dysregulated spermatogenesis of DEHP exposure on the testes of prepubertal rats.</div></div>","PeriodicalId":21137,"journal":{"name":"Reproductive toxicology","volume":"132 ","pages":"Article 108758"},"PeriodicalIF":3.3,"publicationDate":"2024-11-28","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142755393","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}