Selective depletion of AMH-expressing granulosa cells in vivo impairs follicular development and fertility in female mice
Selective depletion of AMH-expressing granulosa cells impairs follicular development and fertility in female mice, but recovery is possible after treatment cessation.
Where it sits
this study against the rest of the hcg (human chorionic gonadotropin) corpusSummary and findings
This study examined the effects of selective depletion of AMH-expressing granulosa cells on follicular development and fertility in AMH-TRECK transgenic female mice. Following repeated diphtheria toxin injections, a reduced number of ovulated oocytes and a low proportion of mature oocytes were observed. Recovery of ovarian weight and follicular development occurred after cessation of treatment.
Abstract
In mammals, ovarian follicle development is a highly coordinated process that underlies female fertility. Granulosa cells expressing anti-Mullerian hormone (AMH) are widely used as a marker of growing follicles. However, the in vivo roles of granulosa cells in follicular development and female fertility remain unclear. Here, we analyzed AMH-toxin receptor-mediated cell knockout (AMH-TRECK) transgenic (Tg) mice on a NOG background, in which AMH-expressing granulosa cells are specifically depleted by diphtheria toxin (DT). We first found that, after a single DT injection into postnatal AMH-TRECK Tg females, AMH-expressing granulosa cells in primary and secondary follicles exhibited cleaved caspase-3 signals 1 day later and were depleted 4 days later. Second, after repeated DT injections weekly from 1 to 7 weeks of age in AMH-TRECK Tg females, antral follicles and corpora lutea were rarely observed, and the numbers of primordial, primary, and secondary follicles were decreased. Following PMSG and hCG stimulation, repeated DT-injected Tg females exhibited a reduced number of ovulated oocytes with a low proportion of mature oocytes, resulting in reduced IVF rates and fertility. Further, after a cessation of repeated DT treatment, ovarian weight and follicular development recovered: the numbers of primary, secondary, and antral follicles were recovered, whereas the primordial follicle pool remains reduced. We conclude that selective depletion of AMH-expressing granulosa cells in vivo impairs follicular development and fertility. Our model enables assessment of the in vivo effects of granulosa cell depletion and may provide a useful platform for future transplantation-based studies to understand complex follicular dynamics.