title: Estrogen receptors in granulosa cells govern meiotic resumption of pre-ovulatory oocytes in mammals.
abstract: In mammals, oocytes are arrested at the diplotene stage of meiosis I until the pre-ovulatory luteinizing hormone (LH) surge triggers meiotic resumption through the signals in follicular granulosa cells. In this study, we show that the estradiol (E2)-estrogen receptors (ERs) system in follicular granulosa cells has a dominant role in controlling oocyte meiotic resumption in mammals. We found that the expression of ERs was controlled by gonadotropins under physiological conditions. E2-ERs system was functional in maintaining oocyte meiotic arrest by regulating the expression of natriuretic peptide C and natriuretic peptide receptor 2 (NPPC/NPR2), which was achieved through binding to the promoter regions of Nppc and Npr2 genes directly. In ER knockout mice, meiotic arrest was not sustained by E2 in most cumulus-oocyte complexes in vitro and meiosis resumed precociously in pre-ovulatory follicles in vivo. In human granulosa cells, similar conclusions are reached that ER levels were controlled by gonadotropins and E2-ERs regulated the expression of NPPC/NPR2 levels. In addition, our results revealed that the different regulating patterns of follicle-stimulating hormone and LH on ER levels in vivo versus in vitro determined their distinct actions on oocyte maturation. Taken together, these findings suggest a critical role of E2-ERs system during oocyte meiotic progression and may propose a novel approach for oocyte in vitro maturation treatment in clinical practice.
authors.affiliation: State Key Laboratory of Agrobiotechnology, College of Biological Sciences, China Agricultural University, No. 2 Yuanmingyuan West Road, Beijing 100193, China.
authors.forename: Wei
authors.initials: W
authors.lastname: Liu
authors.affiliation: State Key Laboratory of Agrobiotechnology, College of Biological Sciences, China Agricultural University, No. 2 Yuanmingyuan West Road, Beijing 100193, China.
authors.forename: Qiliang
authors.initials: Q
authors.lastname: Xin
authors.affiliation: State Key Laboratory of Agrobiotechnology, College of Biological Sciences, China Agricultural University, No. 2 Yuanmingyuan West Road, Beijing 100193, China.
authors.forename: Xiao
authors.initials: X
authors.lastname: Wang
authors.affiliation: Department of Gynecology and Obstetrics, Medical Center of Reproduction and Genetics, Peking University First Hospital, Beijing 100034, China.
authors.forename: Sheng
authors.initials: S
authors.lastname: Wang
authors.affiliation: State Key Laboratory of Agrobiotechnology, College of Biological Sciences, China Agricultural University, No. 2 Yuanmingyuan West Road, Beijing 100193, China.
authors.forename: Huarong
authors.initials: H
authors.lastname: Wang
authors.affiliation: State Key Laboratory of Agrobiotechnology, College of Biological Sciences, China Agricultural University, No. 2 Yuanmingyuan West Road, Beijing 100193, China.|College of Biotechnology, Tianjin University of Science and Technology, Tianjin 300457, China.
authors.forename: Wenqiang
authors.initials: W
authors.lastname: Zhang
authors.affiliation: State Key Laboratory of Agrobiotechnology, College of Biological Sciences, China Agricultural University, No. 2 Yuanmingyuan West Road, Beijing 100193, China.
authors.forename: Ye
authors.initials: Y
authors.lastname: Yang
authors.affiliation: State Key Laboratory of Agrobiotechnology, College of Biological Sciences, China Agricultural University, No. 2 Yuanmingyuan West Road, Beijing 100193, China.
authors.forename: Yanhao
authors.initials: Y
authors.lastname: Zhang
authors.affiliation: State Key Laboratory of Agrobiotechnology, College of Biological Sciences, China Agricultural University, No. 2 Yuanmingyuan West Road, Beijing 100193, China.
authors.forename: Zhiyuan
authors.initials: Z
authors.lastname: Zhang
authors.affiliation: State Key Laboratory of Agrobiotechnology, College of Biological Sciences, China Agricultural University, No. 2 Yuanmingyuan West Road, Beijing 100193, China.
authors.forename: Chao
authors.initials: C
authors.lastname: Wang
authors.affiliation: Department of Gynecology and Obstetrics, Medical Center of Reproduction and Genetics, Peking University First Hospital, Beijing 100034, China.
authors.forename: Yang
authors.initials: Y
authors.lastname: Xu
authors.affiliation: State Key Laboratory of Stem Cell and Reproductive Biology, Institute of Zoology, Chinese Academy of Sciences, Beijing 100101, China.
authors.forename: Enkui
authors.initials: E
authors.lastname: Duan
authors.affiliation: State Key Laboratory of Agrobiotechnology, College of Biological Sciences, China Agricultural University, No. 2 Yuanmingyuan West Road, Beijing 100193, China.
authors.forename: Guoliang
authors.initials: G
authors.lastname: Xia
mesh_terms: D000818:Animals; D005260:Female; D018507:Gene Expression Regulation, Developmental; D006107:Granulosa Cells / Q000378:metabolism; D006801:Humans; D059471:In Vitro Oocyte Maturation Techniques; D007986:Luteinizing Hormone / Q000235:genetics; D008540:Meiosis / Q000235:genetics*; D018345:Mice, Knockout; D020098:Natriuretic Peptide, C-Type / Q000235:genetics*; D009865:Oocytes / Q000254:growth & development; D009866:Oogenesis / Q000235:genetics; D006080:Ovarian Follicle / Q000254:growth & development; D017461:Receptors, Atrial Natriuretic Factor / Q000235:genetics*; D011959:Receptors, Estradiol / Q000235:genetics*; D011960:Receptors, Estrogen / Q000235:genetics*; D000099242:Atrial Natriuretic Factor Receptor B
chemical_list: D007986:Luteinizing Hormone; D020098:Natriuretic Peptide, C-Type; D017461:Receptors, Atrial Natriuretic Factor; D011959:Receptors, Estradiol; D011960:Receptors, Estrogen; D000099242:Atrial Natriuretic Factor Receptor B