JAK signaling regulates germline cyst breakdown and primordial follicle formation in mice

Abstract

In female mammals, primordial follicles consist of two types of cells, namely, oocytes and pregranulosa cells that surround the oocytes. The size of the primordial follicle pool determines the reproductive ability of female mammals. However, the underlying mechanisms controlling primordial follicle assembly remain unclear. In this study, we show that oocyte-derived Janus kinase (JAK) signaling is vital for germline cyst breakdown and primordial follicle formation in vitro. JAK2 and JAK3 activity is increased while germline cysts are breaking down. Inhibition of either JAK2 or JAK3 prevents germline cyst breakdown and primordial follicle formation. We further show that specific suppression of JAK2 delays germ cell loss through the downregulation of p53, but has no influence on pregranulosa cell proliferation. Alternatively, specific inhibition of JAK3 decreases pregranulosa cell proliferation by downregulating Notch2 signaling, implying that JAK3 acts on pregranulosa cells by controlling the extracellular secretion of oocyte-derived factors. In summary, our results indicate that JAK signaling contributes to germline cyst breakdown and primordial follicle formation by regulating oocyte loss and pregranulosa cell proliferation in the fetal mouse ovary. Our findings contribute to a better understanding of the molecular mechanism of mammalian folliculogenesis.