中国科学院重庆绿色智能技术研究院机构知识库

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	Transcriptome and in silico approaches provide new insights into the mechanism of male reproductive toxicity induced by chronic exposure to DEHP
	Ma, Yan-Bo1,2; Manzoor, Rakia2,4; Jia, Pan-Pan1,2; Bian, Wan-Ping1,2; Hamid, Naima1,2; Xie, Zhuo-Yuan1,2; Pei, De-Sheng3
	2021-11-15
摘要	Di-(2-ethylhexyl) phthalate (DEHP) can affect the male reproductive system in vertebrates, but the underlying molecular mechanism is still elusive. Therefore, in this study, we aimed to dig the in-depth mechanism of DEHPinduced reproductive toxicity on male zebrafish via testicular transcriptome using embryo exposed at the environmentally relevant concentration (ERC) of 100 mu g/L for 111 days. Moreover, our results were further confirmed via in silico technique and bioassay experimental in vitro (cell lines) and in vivo (zebrafish). The results showed DEHP exposure could affect male spermatogenesis, altered gonad histology, and reduced egg fertilization rate. Transcriptome analysis identified 1879 significant differentially expressed genes enriched in the exposure group. Twenty-seven genes related to three pathways of reproduction behavior were further validated by qPCR. In silico molecular docking revealed that DEHP and its metabolism bind to the zebrafish progesterone receptor (Pgr), suggesting the potential disruption of DEHP to the normal Pgr signaling. To further validate it, a wild-type Pgr plasmid and its mutants on specific binding sites were constructed. The transfection and microinjection experiment demonstrated that these binding sites mutations of Pgr affected the expression levels of male reproductive toxicity. Taken together, our study provided new insight into the molecular mechanisms of male reproductive toxicity induced by DEHP, and Pgr may serve as an important target binding by DEHP pollution, which needs further study in the future.
关键词	DEHP Progesterone receptor Male zebrafish Reproductive toxicity Chronic exposure
DOI	10.1016/j.envpol.2021.117944
发表期刊	ENVIRONMENTAL POLLUTION
ISSN	0269-7491
卷号	289页码:11
通讯作者	Pei, De-Sheng(peids@cigit.ac.cn)
收录类别	SCI
WOS记录号	WOS:000696650500007
语种	英语