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Bone morphogenetic protein 15 (BMP15) and growth differentiation factor 9 (GDF9) are members of the transforming growth factor beta (TGF-β) superfamily. Through autocrine and paracrine mechanisms, these two factors can regulate cell differentiation, proliferation, and other functions in the ovary locally. Furthermore, GDF9 and BMP15 play vital roles in follicular growth, atresia, ovulation, fertilization, reproduction, and maintenance. Numerous studies have demonstrated a synergy between BMP15 and GDF9. Studies in humans and mice have indicated that the synergy between BMP15 and GDF9 is primarily mediated by the bone morphogenetic protein type II receptor (BMPR2). The BMP15/GDF9 heterodimer needs to bind to the BMPR2-ALK4/5/7-ALK6 receptor complex to activate the SMAD2/3 signaling pathway. However, it is not clear which genes mediate and regulate the effects of the BMP15/GDF9 proteins on bovine cumulus cells (CCs).

Regulatory Role of miRNA-375 in Expression of BMP15/GDF9 Receptors and its Effect on Proliferation and Apoptosis of Bovine Cumulus Cells