title: DEHP exposure impairs mouse oocyte cyst breakdown and primordial follicle assembly through estrogen receptor-dependent and independent mechanisms.
abstract: 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.
authors.affiliation: Laboratory of Reproductive Biology, Chongqing Medical University, Chongqing 400016, PR China; Department of Histology and Embryology, College of Basic Medicine, Chongqing Medical University, Chongqing 400016, PR China.
authors.forename: Xinyi
authors.initials: X
authors.lastname: Mu
authors.affiliation: Laboratory of Reproductive Biology, Chongqing Medical University, Chongqing 400016, PR China.
authors.forename: Xinggui
authors.initials: X
authors.lastname: Liao
authors.affiliation: Laboratory of Reproductive Biology, Chongqing Medical University, Chongqing 400016, PR China.
authors.forename: Xuemei
authors.initials: X
authors.lastname: Chen
authors.affiliation: Laboratory of Reproductive Biology, Chongqing Medical University, Chongqing 400016, PR China.
authors.forename: Yanli
authors.initials: Y
authors.lastname: Li
authors.affiliation: Laboratory of Reproductive Biology, Chongqing Medical University, Chongqing 400016, PR China.
authors.forename: Meirong
authors.initials: M
authors.lastname: Wang
authors.affiliation: Laboratory of Reproductive Biology, Chongqing Medical University, Chongqing 400016, PR China.
authors.forename: Cha
authors.initials: C
authors.lastname: Shen
authors.affiliation: Laboratory of Reproductive Biology, Chongqing Medical University, Chongqing 400016, PR China.
authors.forename: Xue
authors.initials: X
authors.lastname: Zhang
authors.affiliation: Laboratory of Reproductive Biology, Chongqing Medical University, Chongqing 400016, PR China.
authors.forename: Yingxiong
authors.initials: Y
authors.lastname: Wang
authors.affiliation: Laboratory of Reproductive Biology, Chongqing Medical University, Chongqing 400016, PR China.
authors.forename: Xueqing
authors.initials: X
authors.lastname: Liu
authors.affiliation: Laboratory of Reproductive Biology, Chongqing Medical University, Chongqing 400016, PR China. Electronic address: hejunlin_11@aliyun.com.
authors.forename: Junlin
authors.initials: J
authors.lastname: He
mesh_terms: D000818:Animals; D000831:Animals, Newborn; D004051:Diethylhexyl Phthalate / Q000633:toxicity*; D052244:Endocrine Disruptors / Q000633:toxicity*; D004785:Environmental Pollutants / Q000633:toxicity*; D004958:Estradiol / Q000031:analogs & derivatives / Q000494:pharmacology; D004965:Estrogen Antagonists / Q000494:pharmacology; D005260:Female; D000077267:Fulvestrant; D005854:Germ Cells / Q000187:drug effects; D006107:Granulosa Cells / Q000187:drug effects; D051379:Mice; D008807:Mice, Inbred BALB C; D009865:Oocytes / Q000187:drug effects*; D009924:Organ Culture Techniques; D006080:Ovarian Follicle / Q000187:drug effects*; D010968:Plasticizers / Q000633:toxicity*; D011247:Pregnancy; D051883:Receptor, Notch2 / Q000096:biosynthesis; D011960:Receptors, Estrogen / Q000187:drug effects*
chemical_list: D052244:Endocrine Disruptors; D004785:Environmental Pollutants; D004965:Estrogen Antagonists; C497765:Notch2 protein, mouse; D010968:Plasticizers; D051883:Receptor, Notch2; D011960:Receptors, Estrogen; D000077267:Fulvestrant; D004958:Estradiol; D004051:Diethylhexyl Phthalate
keywords: DEHP; Estrogen receptor; Notch signaling; Pregranulosa precursor cell; Primordial follicles assembly