NTRK1 and NTRK2 receptors facilitate follicle assembly and early follicular development in the mouse ovary

Abstract

Recent studies have demonstrated that neurotrophins (NTs) and their NTRK tyrosine kinase receptors, thought to be exclusively required for the development of the nervous system, are also involved in controlling ovarian development. Here, we show that primordial follicle formation is decreased in the absence of nerve growth factor (NGF) or its receptor NTRK1, and in the absence of NTRK2, the receptor for neurotrophin-4 (NTF4) and brain-derived neurotrophic factor (BDNF). This deficiency is not due to premature oocyte loss, because the ovaries of Ntrk1 -/- and Ntrk2 -/- mice do not show an increased rate of oocyte death antedating the initiation of folliculogenesis. Moreover, exposure ofNGF-deficient ovaries toNGF rescues the defect in follicular assembly, if NTRK1 receptors are present, suggesting that the absence of NTs causes a delay, and not an irretrievable loss, of follicle formation. Both the number of secondary follicles and FSH-receptor (FSHR) expression are diminished in Ntrk1-