Autophagy is a cell survival program for female germ cells in the murine ovary

Abstract

It is estimated that infertility affects 15-20% of couples and can arise from female or male reproductive defects. Mouse models have ascribed roles to over 100 genes in the maintenance of female fertility. Although previous models have determined roles for apoptosis in male and female fertility, we find that compromised autophagy within the perinatal ovary, through the loss of Becn1 or Atg7, results in the premature loss of female germ cells. Becn1 C/K ovaries have a 56% reduction of germ cells compared with control ovaries at post-natal day 1, whereas Atg7 K/K ovaries lack discernable germ cells at this stage. Thus autophagy appears to be a cell survival mechanism to maintain the endowment of female germ cells prior to establishing primordial follicle pools in the ovary.

Altering Autophagy: Mouse Models of Human Disease

“…An expression profile of Becn1 mRNA revealed significantly higher expression in primordial follicles than in other stages. Immunohistochemistry for BECN1 confirmed this result and consistent staining of granulose cells, theca cells and oocyte cytoplasm was seen in all follicular stages examined [63]. Interestingly, when Becn1 or Atg7 is ablated specifically in the female germline (MMTV-CreA; Becn1 fl/fl ) or globally (Atg7 -/-), fewer primordial follicles were present in the perinatal ovary.…”

Follicular assembly: mechanisms of action

“…Lysosomal amplification has been observed in oocytes at the time of primordial follicle formation, suggesting that autophagy may occur in newborn ovaries (Rodrigues et al 2009). Newborn female mice with targeted disruption of two different genes (Atg7 and Becn1) encoding proteins involved in autophagy have a greater decrease in oocyte number than wild-type mice supporting a role for autophagy in the regulation of oocyte survival (Gawriluk et al 2011).…”

PI3K/PTEN/Akt and TSC/mTOR signaling pathways, ovarian dysfunction, and infertility: an update

“…The ovary may rely on alternative pathways for cell survival and cell death apart from apoptosis. Autophagy has been demonstrated to be an important regulator of germ cell survival before formation of the primordial follicular pool in murine ovaries (Gawriluk et al 2011).…”