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Foetal-neonatal exposure of Di (2-ethylhexyl) phthalate disrupts ovarian development in mice by inducing autophagy

Authors :
Yan Zhang
Xinyi Mu
Rufei Gao
Yubin Ding
Junlin He
Yuheng Wang
Xueqing Liu
Xuemei Chen
Yanqing Geng
Yingxiong Wang
Source :
Journal of hazardous materials. 358
Publication Year :
2017

Abstract

The female reproductive lifespan is largely determined by the size of the primordial follicle pool, which is established early in life. We previously reported that Di (2-ethylhexyl) phthalate (DEHP), an environmental endocrine disruptor and a widely-spreading plasticizer, impairs primordial folliculogenesis. In the present study, we found DEHP significantly altered the number and sex ratio of the offspring of neonatal-exposed mice. Furthermore, by a neonatal exposure model and an ovary culture model, it showed that DEHP activated autophagy in the ovary, with increased autophagy-related gene expression and recognizable autophagosomes, while inhibition of autophagy by 3-MA attenuated the adverse impact of DEHP on primordial folliculogenesis. Moreover, key components of AMPK-SKP2-CARM1 signalling were up-regulated by DEHP in the ovary, and AMPK inhibitor Compound C reduced autophagy-related gene expression and partially recovered primordial follicle assembly. Collectively, this study demonstrates that DEHP induces autophagy by activating AMPK-SKP2-CARM1 signalling in mice perinatal ovaries, which results in disrupted primordial folliculogenesis and reduced female fertility.

Details

ISSN :
18733336
Volume :
358
Database :
OpenAIRE
Journal :
Journal of hazardous materials
Accession number :
edsair.doi.dedup.....9284ed7949185ec002490d795bcc75b9