Induction of Ovarian Primordial Follicle Assembly by Connective Tissue Growth Factor CTGF

Primordial follicle assembly is a process that occurs when oocyte nests break down to form individual primordial follicles. The size of this initial pool of primordial follicles in part determines the reproductive lifespan of the female. Connective tissue growth factor (CTGF) was identified as a potential regulatory candidate for this process in a previous microarray analysis of follicle development. The current study examines the effects of CTGF and associated transforming growth factor beta 1 (TGF beta-1) on follicle assembly. Ovaries were removed from newborn rat pups and placed in an organ culture system. The ovaries treated with CTGF for two days were found to have an increased proportion of assembled follicles. CTGF was found to regulate the ovarian transcriptome during primordial follicle assembly and an integrative network of genes was identified. TGF beta-1 had no effect on primordial follicle assembly and in combination with CTGF decreased oocyte number in the ovary after two days of culture. Over ten days of treatment only the combined treatment of CTGF and TGF beta-1 was found to cause an increase in the proportion of assembled follicles. Interestingly, treatment with TGF beta-1 alone resulted in fewer total oocytes in the ovary and decreased the primordial follicle pool size after ten days of culture. Observations indicate that CTGF alone or in combination with TGF beta-1 stimulates primordial follicle assembly and TGF beta-1 can decrease the primordial follicle pool size. These observations suggest the possibility of manipulating primordial follicle pool size and influencing female reproductive lifespan.