|BMP‑15/GDF‑9B in Mouse Ovary. BMP‑15/GDF‑9B was detected in immersion fixed frozen sections of mouse ovary using 10 µg/mL Rat Anti-Human BMP‑15/GDF‑9B Monoclonal Antibody (Catalog # MAB2925) overnight at 4 °C. Tissue was stained with the NorthernLights™ 557-conjugated Anti-Rat IgG Secondary Antibody (red; Catalog # NL013) and counterstained with DAPI (blue). View our protocol for Fluorescent IHC Staining of Frozen Tissue Sections.|
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.
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