The effect of hepatocyte growth factor on the initial stages of mouse follicle development

Interactions between theca and granulosa cells of the follicle are critical for the coordination of ovarian follicle development. The cell–cell interactions are mediated through the local production and actions of a variety of factors. The current study is designed to investigate the expression of Hgf and its receptor, c‐Met, in the mouse ovary during in vivo folliculogenesis. We found that Hgf and c‐Met mRNAs were already expressed in 2‐day‐old ovaries, and that, while c‐Met levels remained constant until 22‐day‐old, Hgf levels slightly but not significantly increased with age. The expression of Hgf mRNA in theca/interstitial cells was higher than in granulosa cells in 22‐day‐old ovaries. Immunohistochemistry analysis confirmed the expression pattern demonstrated by RT‐PCR. We investigated the role of hepatocyte growth factor (HGF) at the beginning of mouse folliculogenesis and its possible interaction with kit ligand (KL). Interestingly, both KL and HGF were able to increase the expression of each other, creating a positive feedback loop. In the presence of HGF, we observed an increase of granulosa cell proliferation and an increase in the number of pre‐antral and early antral follicles in ovary organ cultures. We also observed a significant increase in the diameters of follicles in individual follicle cultures. Moreover, HGF stimulated the expression of the FSH receptors, both in the whole ovary and in isolated pre‐antral follicle cultures. Based on the data presented, we concluded that HGF exerts multiple levels of control over follicular cell functions, which collectively enable the progression of follicular development. J. Cell. Physiol. 226: 520–529, 2011. © 2010 Wiley‐Liss, Inc.