title: ADAM10-Notch signaling governs the recruitment of ovarian pregranulosa cells and controls folliculogenesis in mice.
abstract: Ovarian follicles are the basic functional units of female reproduction in the mammalian ovary. We show here that the protein a disintegrin and metalloproteinase domain 10 (ADAM10), a cell surface sheddase, plays an indispensable role in controlling primordial follicle formation by regulating the recruitment of follicle supporting cells in mice. We demonstrate that suppressing ADAM10 in vitro or deletion of Adam10 in vivo disrupts germline cyst breakdown and primordial follicle formation. Using a cell lineage tracing approach, we show that ADAM10 governs the recruitment of ovarian follicle cells by regulating the differentiation and proliferation of LGR5-positive follicle supporting progenitor cells. By detecting the development of FOXL2-positive pregranulosa cells, we found that inhibiting ADAM10 reduced the number of FOXL2-positive cells in perinatal ovaries. Furthermore, inhibiting ADAM10 suppressed the activation of Notch signaling, and blocking Notch signaling also disrupted the recruitment of follicle progenitor cells. Taken together, these results show that ADAM10-Notch signaling in ovarian somatic cells governs the primordial follicle formation by controlling the development of ovarian pregranulosa cells. The proper recruitment of ovarian follicle supporting cells is essential for establishment of the ovarian reserve in mice.
authors.affiliation: State Key Laboratory of Agrobiotechnology, College of Biological Science, China Agricultural University, Beijing 100193, China.
authors.forename: Lizhao
authors.initials: L
authors.lastname: Feng
authors.affiliation: National Institute of Biological Sciences, Beijing 102206, China.
authors.forename: Yijing
authors.initials: Y
authors.lastname: Wang
authors.affiliation: State Key Laboratory of Agrobiotechnology, College of Biological Science, China Agricultural University, Beijing 100193, China.
authors.forename: Han
authors.initials: H
authors.lastname: Cai
authors.affiliation: State Key Laboratory of Agrobiotechnology, College of Biological Science, China Agricultural University, Beijing 100193, China.
authors.forename: Guanghong
authors.initials: G
authors.lastname: Sun
authors.affiliation: State Key Laboratory of Agrobiotechnology, College of Biological Science, China Agricultural University, Beijing 100193, China.
authors.forename: Wanbao
authors.initials: W
authors.lastname: Niu
authors.affiliation: State Key Laboratory of Agrobiotechnology, College of Biological Science, China Agricultural University, Beijing 100193, China.
authors.forename: Qiliang
authors.initials: Q
authors.lastname: Xin
authors.affiliation: State Key Laboratory of Reproductive Biology, Institute of Zoology, Chinese Academy of Sciences, Beijing 100101, China.
authors.forename: Xiaofang
authors.initials: X
authors.lastname: Tang
authors.affiliation: State Key Laboratory of Agrobiotechnology, College of Biological Science, China Agricultural University, Beijing 100193, China.
authors.forename: Jiawei
authors.initials: J
authors.lastname: Zhang
authors.affiliation: State Key Laboratory of Agrobiotechnology, College of Biological Science, China Agricultural University, Beijing 100193, China.
authors.forename: Chao
authors.initials: C
authors.lastname: Wang
authors.affiliation: State Key Laboratory of Agrobiotechnology, College of Biological Science, China Agricultural University, Beijing 100193, China glxiachina@sohu.com huazhang@cau.edu.cn.
authors.forename: Hua
authors.identifier: 0000-0002-4700-5971
authors.initials: H
authors.lastname: Zhang
authors.affiliation: State Key Laboratory of Agrobiotechnology, College of Biological Science, China Agricultural University, Beijing 100193, China glxiachina@sohu.com huazhang@cau.edu.cn.
authors.forename: Guoliang
authors.identifier: 0000-0003-3674-0142
authors.initials: G
authors.lastname: Xia
mesh_terms: D000072197:ADAM10 Protein / Q000378:metabolism*; D000818:Animals; D000831:Animals, Newborn; D002454:Cell Differentiation; D049109:Cell Proliferation; D005260:Female; D000074842:Forkhead Box Protein L2; D051858:Forkhead Transcription Factors / Q000378:metabolism; D005854:Germ Cells / Q000378:metabolism; D006107:Granulosa Cells / Q000166:cytology / Q000378:metabolism*; D051379:Mice; D038081:Organogenesis; D043562:Receptors, G-Protein-Coupled / Q000378:metabolism; D051880:Receptors, Notch / Q000378:metabolism*; D015398:Signal Transduction; D013234:Stem Cells / Q000166:cytology / Q000378:metabolism
chemical_list: D000074842:Forkhead Box Protein L2; D051858:Forkhead Transcription Factors; C498893:Foxl2 protein, mouse; C493597:Lgr5 protein, mouse; D043562:Receptors, G-Protein-Coupled; D051880:Receptors, Notch; D000072197:ADAM10 Protein
keywords: ADAM10; FOXL2; LGR5; Notch signaling; Pregranulosa cell recruitment; Primordial follicle formation