{"title":"piRNA array analysis provide insight into the mechanism of DEHP-induced testicular toxicology in pubertal male rats","authors":"","doi":"10.1016/j.ecoenv.2024.117282","DOIUrl":null,"url":null,"abstract":"<div><div>Di-(2-ethylhexyl) phthalate (DEHP), a widely used plasticizer, could cause male reproductive toxicity by disrupting spermatogenesis. Piwi-interacting RNAs (piRNAs) are a small non-coding RNAs specifically highly expressed in the germline and interact with PIWI proteins to regulate spermatogenesis. Accumulating studies have confirmed that environmental poisons could induce male reproductive injury via altering piRNA expression. However, it remains unclear whether DEHP causes male reproductive dysfunction by perturbing piRNA expression levels. In this study, we conducted piRNA microarray expression analyses on testes of DEHP-exposed and control male rats and performed some <em>in vitro</em> and <em>in vivo</em> studies to explore the role of piRNA on DEHP-induced male reproductive toxicity. Our results showed that DEHP exposure leaded to changed expression profiles of piRNAs in pubertal male rat testes. And bioinformatics analyses revealed that down-regulated piR-rno-26751 probably targeted <em>Insr</em> mRNA expression regulation. Results from gene and protein expression tests demonstrated that DEHP caused decreased expression level of INSR mainly in spermatogonia. Moreover, MEHP, the main metabolite of DEHP resulted in cell apoptosis and down-regulation of INSR and its downstream p-IRS1, p-PI3K, p-AKT and p-FOXO1 in GC-1spg cells. Conversely, overexpression of INSR restored cell apoptosis and the down-regulation of the above proteins in GC-1spg cells. In conclusion, these findings suggest that DEHP-induced down-regulation of piR-rno-26751 targets the suppression of INSR, leading to apoptosis of spermatogonia in pubertal male rats.</div></div>","PeriodicalId":303,"journal":{"name":"Ecotoxicology and Environmental Safety","volume":null,"pages":null},"PeriodicalIF":6.2000,"publicationDate":"2024-11-05","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":"0","resultStr":null,"platform":"Semanticscholar","paperid":null,"PeriodicalName":"Ecotoxicology and Environmental Safety","FirstCategoryId":"93","ListUrlMain":"https://www.sciencedirect.com/science/article/pii/S0147651324013587","RegionNum":2,"RegionCategory":"环境科学与生态学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":null,"EPubDate":"","PubModel":"","JCR":"Q1","JCRName":"ENVIRONMENTAL SCIENCES","Score":null,"Total":0}
引用次数: 0
Abstract
Di-(2-ethylhexyl) phthalate (DEHP), a widely used plasticizer, could cause male reproductive toxicity by disrupting spermatogenesis. Piwi-interacting RNAs (piRNAs) are a small non-coding RNAs specifically highly expressed in the germline and interact with PIWI proteins to regulate spermatogenesis. Accumulating studies have confirmed that environmental poisons could induce male reproductive injury via altering piRNA expression. However, it remains unclear whether DEHP causes male reproductive dysfunction by perturbing piRNA expression levels. In this study, we conducted piRNA microarray expression analyses on testes of DEHP-exposed and control male rats and performed some in vitro and in vivo studies to explore the role of piRNA on DEHP-induced male reproductive toxicity. Our results showed that DEHP exposure leaded to changed expression profiles of piRNAs in pubertal male rat testes. And bioinformatics analyses revealed that down-regulated piR-rno-26751 probably targeted Insr mRNA expression regulation. Results from gene and protein expression tests demonstrated that DEHP caused decreased expression level of INSR mainly in spermatogonia. Moreover, MEHP, the main metabolite of DEHP resulted in cell apoptosis and down-regulation of INSR and its downstream p-IRS1, p-PI3K, p-AKT and p-FOXO1 in GC-1spg cells. Conversely, overexpression of INSR restored cell apoptosis and the down-regulation of the above proteins in GC-1spg cells. In conclusion, these findings suggest that DEHP-induced down-regulation of piR-rno-26751 targets the suppression of INSR, leading to apoptosis of spermatogonia in pubertal male rats.
期刊介绍:
Ecotoxicology and Environmental Safety is a multi-disciplinary journal that focuses on understanding the exposure and effects of environmental contamination on organisms including human health. The scope of the journal covers three main themes. The topics within these themes, indicated below, include (but are not limited to) the following: Ecotoxicology、Environmental Chemistry、Environmental Safety etc.