Recombinant Human BMP-15 Protein

Bone morphogenetic protein 15 (BMP-15), also known as GDF-9B, is a TGF-beta superfamily ligand that is expressed by oocytes throughout folliculogenesis, and plays an important role in oocyte development (1). BMP-15 promotes the FSH‑independent proliferation of ovarian granulosa cells (GC) and induces GC glycolysis and cholesterol synthesis (2‑4). It also induces GC production of stem cell factor which, in turn, negatively regulates BMP-15 expression in oocytes (5). BMP-15 blocks the FSH‑induced GC expression of FSH R and multiple steroidogenic molecules (6). BMP-15 is synthesized with a 249 amino acid (aa) N-terminal propeptide (7). The propeptide is cleaved intracellularly from the 50 kDa proBMP-15 but remains associated with mature BMP-15 (8). Mature BMP-15 exists in 16 kDa and 17 kDa forms which are distinguishable by the presence of O-linked glycosylation on the 17 kDa form (8). Mature BMP-15 is phosphorylated, a modification which is required for the stimulation of GC proliferation (9). BMP-15 exerts its effects through interactions with BMPR‑IB/ALK6 and BMPR‑II (9-11). Mature BMP-15 forms 34 kDa noncovalently-linked homodimers and 37 kDa heterodimers with mature GDF-9 (12). Both of these oocyte-expressed factors lack the cysteine that mediates disulfide-linked dimerization in most TGF-beta superfamily ligands (1). Although heterodimerization with GDF-9 may limit the secretion of active BMP‑15, these two factors synergize in promoting oocyte survival and folliculogenesis (12, 13). Mature human BMP-15 shares 70%, 68%, and 78% aa sequence identity with mouse, rat, and sheep BMP-15, respectively. It shares 27%-38% aa sequence with other BMPs.