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J Cell Sci. 2016 Jun 1;129(11):2202-12. doi: 10.1242/jcs.184267. Epub 2016 Apr 15.

ADAM10-Notch signaling governs the recruitment of ovarian pregranulosa cells and controls folliculogenesis in mice.

Author information

1
State Key Laboratory of Agrobiotechnology, College of Biological Science, China Agricultural University, Beijing 100193, China.
2
National Institute of Biological Sciences, Beijing 102206, China.
3
State Key Laboratory of Reproductive Biology, Institute of Zoology, Chinese Academy of Sciences, Beijing 100101, China.
4
State Key Laboratory of Agrobiotechnology, College of Biological Science, China Agricultural University, Beijing 100193, China glxiachina@sohu.com huazhang@cau.edu.cn.

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.

KEYWORDS:

ADAM10; FOXL2; LGR5; Notch signaling; Pregranulosa cell recruitment; Primordial follicle formation

PMID:
27084580
DOI:
10.1242/jcs.184267
[Indexed for MEDLINE]
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