DEHP exposure impairs mouse oocyte cyst breakdown and primordial follicle assembly through estrogen receptor-dependent and independent mechanisms

• Published in: Journal of hazardous materials 2015-11, Vol.298, p.232-240
• Main Authors: Mu, Xinyi, Liao, Xinggui, Chen, Xuemei, Li, Yanli, Wang, Meirong, Shen, Cha, Zhang, Xue, Wang, Yingxiong, Liu, Xueqing, He, Junlin
• Format: Article
• Language: English
• Subjects: Animals; Animals, Newborn; Assembly; Breakdown; Cysts; DEHP; Diethylhexyl Phthalate - toxicity; Endocrine Disruptors - toxicity; Environmental Pollutants - toxicity; Estradiol - analogs & derivatives; Estradiol - pharmacology; Estrogen Antagonists - pharmacology; Estrogen receptor; Estrogens; Exposure; Female; Germ Cells - drug effects; Granulosa Cells - drug effects; Mice; Mice, Inbred BALB C; Notch signaling; Oocytes - drug effects; Organ Culture Techniques; Ovarian Follicle - drug effects; Ovaries; Plasticizers; Plasticizers - toxicity; Pregnancy; Pregranulosa precursor cell; Primordial follicles assembly; Receptor, Notch2 - biosynthesis; Receptors; Receptors, Estrogen - drug effects
• ISSN: 0304-3894; 1873-3336
• DOI: 10.1016/j.jhazmat.2015.05.052

•DEHP inhibits primordial folliculogenesis in vivo and in vitro.•Estrogen receptors participate in the effect of DEHP on early ovarian development.•DEHP exposure impairs the expression of Notch2 signaling components.•DEHP exposure disrupts the proliferation of pregranulosa precursor cells. Estrogen plays an essential role in the development of mammalian oocytes, and recent studies suggest that it also regulates primordial follicle assembly in the neonatal ovaries. During the last decade, potential exposure of humans and animals to estrogen-like endocrine disrupting chemicals has become a growing concern. In the present study, we focused on the effect of diethylhexyl phthalate (DEHP), a widespread plasticizer with estrogen-like activity, on germ-cell cyst breakdown and primordial follicle assembly in the early ovarian development of mouse. Neonatal mice injected with DEHP displayed impaired cyst breakdown. Using ovary organ cultures, we revealed that impairment was mediated through estrogen receptors (ERs), as ICI 182,780, an efficient antagonist of ER, reversed this DEHP-mediated effect. DEHP exposure reduced the expression of ERβ, progesterone receptor (PR), and Notch2 signaling components. Finally, DEHP reduced proliferation of pregranulosa precursor cells during the process of primordial folliculogenesis. Together, our results indicate that DEHP influences oocyte cyst breakdown and primordial follicle formation through several mechanisms. Therefore, exposure to estrogen-like chemicals during fetal or neonatal development may adversely influence early ovarian development.