Journal
JOURNAL OF HAZARDOUS MATERIALS
Volume 358, Issue -, Pages 101-112Publisher
ELSEVIER
DOI: 10.1016/j.jhazmat.2018.06.042
Keywords
DEHP; Primordial folliculogenesis; Autophagy; AMPK-SKP2-CARM1
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Funding
- National Natural Science Foundation of China [31571554, 31271246]
- Scientific and Technological Research Program of Chongqing Municipal Education Commission [KJ1500226]
- Research and Innovation Projects of Chongqing Municipal Education Commission [CYS16141]
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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.
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