Abstract
Significance This study improves our understanding of the role of Müllerian inhibiting substance (MIS/AMH) in antagonizing primordial follicle activation. By applying scRNA-seq methods to neonatal mouse ovaries, we revealed transcriptional signatures associated with MIS treatment in ovarian cell types present during the first wave of folliculogenesis and follicle development. We showed that MIS inhibits pregranulosa cell differentiation and the proliferation of ovarian surface epithelium and stromal cells. MIS also uncoupled granulosa and germ cell maturation, leading to abnormal development of activated follicles. These findings identify markers and pathways related to primordial follicle quiescence that could be targeted in contraception, preservation of ovarian reserve during aging or chemotherapy, or synchronization of preantral follicle growth for IVF.
Highlights
Müllerian inhibiting substance (MIS/anti-Müllerian hormone (AMH)), produced by granulosa cells of growing follicles, is an important regulator of folliculogenesis and follicle development
Following germ-cyst breakdown, expression was maintained in ovarian surface epithelium (OSE), and granulosa cells of primordial, primary, and early secondary follicles at PND6, a pattern that was retained in the adult with the addition of large antral follicles (SI Appendix, Fig. S1D)
Female mammalian gonads are endowed with an allotment of follicles during the perinatal period, which is expended over the reproductive life span
Summary
Müllerian inhibiting substance (MIS/AMH), produced by granulosa cells of growing follicles, is an important regulator of folliculogenesis and follicle development. | | | Müllerian inhibiting substance ovarian reserve ovary | granulosa cells scRNA-seq ovulation of an oocyte, a process that continues iteratively until menopause [7]. Individual follicles are formed as a result of the breakdown of germ cell-containing cysts, and the invasion of somatic pregranulosa cells that envelop individual oocytes to form a single layer of flattened granulosa cells that characterize the primordial follicle. The timing of this process differs among mammals, occurring during fetal development in humans, at around 18 wk postfertilization [2], or immediately after birth in rodents [3], between postnatal day 1 (PND1) and PND3. While most activated follicles succumb to atresia, in a small subset, the process culminates, after puberty, with the release or
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