Endocrine Abstracts

Bone morphogenetic protein 8 (Bmp8) is important for postnatal gonad functions. Targeted depletion of either Bmp8a or Bmp8b has been shown to cause male infertility due to the degeneration of germ cells. However, no direct signaling pathway of BMP8 has been clarified in vitro due to the lack of functional BMP8 proteins. Of interest, we found that Bmp8 transcripts are not only abundant in the rat testis but also in the ovary. Therefore, we aimed to unveil the BMP8 downstream and characterize its functions in the ovary. Firstly, we generated recombinant BMP8 proteins and found that the bioactive BMP8 proteins mediate the BMP signaling by promoting the phosphorylation of Smad1/5/8. Overexpression of either ALK3 or AKL6 in cells enhances the BMP8 signaling, indicating they are the type 1 receptors of BMP8. In addition, shRNA knockdown experiments demonstrated that ACVR2A and BMPR2 can serve as the type 2 receptors for BMP8. Using a rat superovulation model, we found that Bmp8 transcripts can be upregulated by the LH signaling. Microdissection in combination with mRNA quantification indicated that Bmp8 is mainly located in the cumulus cell–oocyte complex. Treatment with recombinant BMP8 in vitro significantly induced expansion of the cumulus cell–oocyte complex isolated from preovulatory follicles. Taken together, these results suggest that BMP8 may promote female fertility by inducing cumulus cell expansion through the Smad1/5/8 pathway.