Long-term exposure to the mixture of phthalates induced male reproductive toxicity in rats and the alleviative effects of quercetin

Toxicology and Applied Pharmacology, Год журнала: 2024, Номер 483, С. 116816 - 116816

Опубликована: Янв. 11, 2024

Язык: Английский

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Plin4 exacerbates cadmium-decreased testosterone level via inducing ferroptosis in testicular Leydig cells

Redox Biology, Год журнала: 2024, Номер 76, С. 103312 - 103312

Опубликована: Авг. 17, 2024

Strong evidence indicates that environmental stressors are the risk factors for male testosterone deficiency (TD). However, mechanisms of stress-induced TD remain unclear. Based on our all-cause reproductive cohort, we found serum ferrous iron (Fe

Язык: Английский

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Discovery of phloridzin as a new antagonist for Di(2-ethylhexyl) phthalate-induced male reproductive toxicity based on the adverse outcome pathway network and drug-target gene set enrichment analysis

Ecotoxicology and Environmental Safety, Год журнала: 2025, Номер 290, С. 117740 - 117740

Опубликована: Янв. 1, 2025

Di(2-ethylhexyl) phthalate (DEHP) is a widespread ubiquitous environmental contaminant. The male reproductive toxicity (MRT) from exposure to DEHP and its main metabolite, mono(2-ethylhexyl) (MEHP), has been well documented. Fully elucidating toxic mechanism discovering effective antagonists are desirable means reduce the health risks of DEHP. In this study, 552 genes related MRT induced by DEHP/MEHP were screened out Comparative Toxicogenomics Database (CTD) DisGeNET database. Next, we developed global adverse outcome pathway (AOP) network based on existed AOP-wiki. After functional enrichment analyses mapping AOP network, found that increased ROS level, cell cycle arrest, apoptosis key events (KEs) involved in DEHP-mediated MRT, which was validated TM3 Leydig model. Among them, cellular core KE DEHP-induced via topological analysis. Eventually, novel silico antagonist screening platform (http://43.136.69.224:3838/wlab/) drug-target gene set analysis (dtGSEA version 2.0). Several potential candidates mitigate have out, including quercetin, taurine, methionine, phloridzin. Further experimental results demonstrated phloridzin provided most protection against MEHP-induced cells probably through p53 MAPK signaling pathways. Molecular docking molecular dynamics simulations suggest STAT3 RUNX1 may be important targets for antagonize MRT. Our study provides new approach discover contaminants dtGSEA methods.

Язык: Английский

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GSTA2 overexpression alleviates bis (2-ethylhexyl) phthalate (DEHP)-induced male reproductive disorders by inhibiting oxidative stress-mediated cell apoptosis via the activated PI3K/AKT signaling pathway

Molecular and Cellular Endocrinology, Год журнала: 2025, Номер unknown, С. 112462 - 112462

Опубликована: Янв. 1, 2025

Язык: Английский

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Assessing the impact of sub-chronic polyethylene terephthalate nanoplastic exposure on male reproductive health in mice

Toxicology and Applied Pharmacology, Год журнала: 2025, Номер 495, С. 117235 - 117235

Опубликована: Янв. 19, 2025

Язык: Английский

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Cresyl Diphenyl Phosphate exposure induces reproductive functional defects in men and male mice

Ecotoxicology and Environmental Safety, Год журнала: 2024, Номер 271, С. 116003 - 116003

Опубликована: Янв. 28, 2024

Cresyl Diphenyl Phosphate (CDP), as a novel organophosphate esters (OPEs), achieves widely used and exposed in multiple industries. However, its male reproductive toxicity underlying mechanism remains unclear. In vivo, mice were gavaged with CDP (0, 4, 20, or 100 mg/kg/d) for 8 weeks. And we treated TM3, TM4 GC-2 cells 0, 10, 25, 50 μM 24 h to detect effect vitro. our study, revealed that inhibited proliferation induced apoptosis testis cells, thereby leading the decreased sperm quality. mechanism, trigger oxidative stress ROS production, thus partially causing DNA damage cell apoptosis. Moreover, exposure causes injury Ledyig Sertoli disturbing testicular microenvironment inhibiting spermatogonia proliferation. conclusion, this research reveals adverse impacts of on system calls further study toxicological effects human health.

Язык: Английский

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Mono-(2-ethylhexyl) Phthalate (MEHP)-Induced Telomere Structure and Function Disorder Mediates Cell Cycle Dysregulation and Apoptosis via c-Myc and Its Upstream Transcription Factors in a Mouse Spermatogonia-Derived (GC-1) Cell Line

Toxics, Год журнала: 2023, Номер 11(5), С. 448 - 448

Опубликована: Май 10, 2023

As a typical environmental endocrine disrupting chemical (EDC), di-(2-ethylhexyl) phthalate (DEHP) is thought to be related reproductive disorders, especially in males. Growing evidence suggests that various EDCs may result an impaired telomere structure and function, which associated with male infertility. However, the adverse effect of DEHP on telomeres cells has rarely been studied, mechanisms remain unclear. In this study, we tested effects mono-(2-ethylhexyl) (MEHP), primary metabolite DEHP, dysfunction mouse spermatogonia-derived (GC-1) potential role TERT c-Myc MEHP-induced spermatogenic cell damage. Results showed MEHP induced viability inhibition, G0/G1 phase cycle arrest, apoptosis GC-1 dose-dependent manner. Shortened telomeres, reduced telomerase activity, decreased expression TERT, c-Myc, upstream transcription factors were also observed MEHP-treated cells. conclusion, it can concluded TERT-mediated contribute arrest through impairment its factors.

Язык: Английский

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Advances in immunology of male reproductive toxicity induced by common environmental pollutants

Environment International, Год журнала: 2024, Номер 190, С. 108898 - 108898

Опубликована: Июль 20, 2024

Humans are exposed to an ever-increasing number of environmental toxicants, some which have gradually been identified as major risk factors for male reproductive health, even associated with infertility. Male infertility is usually due the system damage, may be influenced by exposure contaminants such heavy metals, plasticizers, along genetics and lifestyle. Testicular immune microenvironment (TIM) important in maintaining normal physiological functions testis, whether disturbed TIM after toxicants could induce toxicity remains explored. Therefore, current review aims contribute further understanding characterizing exposures effect on TIM. We first summarized phenotypes induced common pollutants. Contaminants including metals plastic additives fine particulate matter (PM

Язык: Английский

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Alleviative effect of quercetin against reproductive toxicity induced by chronic exposure to the mixture of phthalates in male rats

Ecotoxicology and Environmental Safety, Год журнала: 2024, Номер 270, С. 115920 - 115920

Опубликована: Янв. 1, 2024

Phthalates (PEs) are widely used plasticizers in polymer products, and humans increasingly exposed to them. This study was designed investigate the alleviative effect of phytochemicals quercetin (Que) against male reproductive toxicity caused by mixture three commonly PEs (MPEs), further explore underlying mechanism. Forty-eight SD rats were randomly evenly divided into control group, Que MPEs group MPEs+Que (n = 12); The oral exposure doses 450 mg/kg/d 50 mg/kg/d, respectively. After 91 days continuous intervention, compared with testes weight, epididymis serum sex hormones, anogenital distance significantly decreased (P < 0.05); Testicular histopathological observation showed that all seminiferous tubules atrophy, leydig cells hyperplasia, spermatogenic growth arrested group. Ultrastructural testicular germ edges nuclear membranes indistinct, mitochondria severely damaged cristae disrupted, or even disappeared Immunohistochemistry Western blot analysis CYP11A1, CYP17A1 17β-HSD up-regulated, while StAR, PIWIL1 PIWIL2 down-regulated However, alterations these parameters restored results indicated disturbed steroid hormone metabolism, injuries; whereas, could inhibit MPEs' toxicity, which might relate regulation metabolism.

Язык: Английский

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N-acetylcysteine alleviated tris(2-chloroisopropyl) phosphate-induced sperm motility decline and functional dysfunction in mice through reversing oxidative stress and DNA damage

Ecotoxicology and Environmental Safety, Год журнала: 2024, Номер 271, С. 116000 - 116000

Опубликована: Янв. 23, 2024

The decline in male fertility caused by environmental pollutants has attracted worldwide attention nowadays. Tris(2-chloroisopropyl) phosphate (TCPP) is a chlorine-containing organophosphorus flame retardant applied many consumer products and multiple side effects on health. However, whether TCPP impairs spermatogenesis remains unclear. In this study, we found that reduced the sperm motility blastocyst formation, inhibited proliferation induced apoptosis mice testes spermatocyte cell line GC-2. Moreover, imbalance of oxidant anti-oxidant, DNA damage mitochondrial dysfunction, thus abnormal spermatogenesis. process, p53 signaling pathway was activated N-acetylcysteine treatment partially alleviated TCPP, including decrease motility, activation damage. Finally, our study verified elevated reactive oxygen species (ROS), decreased membrane potential human semen samples. Overall, ROS mediated TCPP-induced germ inhibition apoptosis, which finally led to motility.

Язык: Английский

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