Open AccessSingle-cell sequencing reveals suppressive transcriptional programs regulated by MIS/AMH in neonatal ovaries
Author(s) -
Marie-Charlotte Meinsohn,
Hatice D. Saatcioglu,
Lina Wei,
Yang Li,
Heiko Horn,
Maëva Chauvin,
Mariko Kano,
Ngoc Minh Nguyen,
Nicholas Nagykery,
A Kashiwagi,
Wesley Samore,
Dan Wang,
Esther Oliva,
Guangping Gao,
Mary E. Morris,
Patricia K. Donahoe,
David Pépin
Publication year - 2021
Publication title -
proceedings of the national academy of sciences of the united states of america
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 5.011
H-Index - 771
eISSN - 1091-6490
pISSN - 0027-8424
DOI - 10.1073/pnas.2100920118
Subject(s) - folliculogenesis , follicle , biology , microbiology and biotechnology , ovarian follicle , cell growth , regulator , stromal cell , oocyte , ovulation , granulosa cell , medicine , ovary , germ cell , andrology , cell , endocrinology , embryogenesis , embryo , gene , cancer research , hormone , genetics
Müllerian inhibiting substance (MIS/AMH), produced by granulosa cells of growing follicles, is an important regulator of folliculogenesis and follicle development. Treatment with exogenous MIS in mice suppresses follicle development and prevents ovulation. To investigate the mechanisms by which MIS inhibits follicle development, we performed single-cell RNA sequencing of whole neonatal ovaries treated with MIS at birth and analyzed at postnatal day 6, coinciding with the first wave of follicle growth. We identified distinct transcriptional signatures associated with MIS responses in the ovarian cell types. MIS treatment inhibited proliferation in granulosa, surface epithelial, and stromal cell types of the ovary and elicited a unique signature of quiescence in granulosa cells. In addition to decreasing the number of growing preantral follicles, we found that MIS treatment uncoupled the maturation of germ cells and granulosa cells. In conclusion, MIS suppressed neonatal follicle development by inhibiting proliferation, imposing a quiescent cell state, and preventing granulosa cell differentiation.