Bone morphogenetic protein 15 and fibroblast growth factor 10 enhance cumulus expansion, glucose uptake, and expression of genes in the ovulatory cascade during in vitro maturation of bovine cumulus–oocyte complexes

Abstract

Oocyte-secreted factors (OSFs) regulate differentiation of cumulus cells and are of pivotal relevance for fertility. Bone morphogenetic protein 15 (BMP15) and fibroblast growth factor 10 (FGF10) are OSFs and enhance oocyte competence by unknown mechanisms. We tested the hypothesis that BMP15 and FGF10, alone or combined in the maturation medium, enhance cumulus expansion and expression of genes in the preovulatory cascade and regulate glucose metabolism favouring hyaluronic acid production in bovine cumulus–oocyte complexes (COCs). BMP15 or FGF10 increased the percentage of fully expanded COCs, but the combination did not further stimulate it. BMP15 increased cumulus cell levels of mRNA encoding a disintegrin and metalloprotease 10 (ADAM10), ADAM17, amphiregulin (AREG), and epiregulin (EREG) at 12 h of culture and of prostaglandin (PG)-endoperoxide synthase 2 (PTGS2), pentraxin 3 (PTX3) and tumor necrosis factor alpha-induced protein 6 (TNFAIP6 (TSG6)) at 22 h of culture. FGF10 did not alter the expression of epidermal growth factor-like factors but enhanced the mRNA expression of PTGS2 at 4 h, PTX3 at 12 h, and TNFAIP6 at 22 h. FGF10 and BMP15 stimulated glucose consumption by cumulus cells but did not affect lactate production or levels of mRNA encoding glycolytic enzymes phosphofructokinase and lactate dehydrogenase A. Each growth factor increased mRNA encoding glucosamine:fructose-6-PO4 transaminases, key enzymes in the hexosamine pathway leading to hyaluronic acid production, and BMP15 also stimulated hyaluronan synthase 2 (HAS2) mRNA expression. This study provides evidence that BMP15 and FGF10 stimulate expansion of in vitro-matured bovine COCs by driving glucose metabolism toward hyaluronic acid production and controlling the expression of genes in the ovulatory cascade, the first acting upon ADAM10, ADAM17, AREG, and EREG and the second on downstream genes, particularly PTGS2.

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

“…Moreover, BMP15 can significantly inhibit apoptosis and promote proliferation in CCs. BMP15 also induces particular gene expression in CCs, such as HAS2, PTX3, and PTGS2, and thereby facilitates CC expansion, optimizes the microenvironment of oocytes, and promotes oocyte maturation and ovulation [30][31][32][33]. GDF9, which has similar functions as BMP15, can inhibit LH/CG receptor and KIT ligand expression in CCs, induce CC expansion-associated gene expression, and facilitate oocyte maturation and ovulation [34][35][36].…”

Maternal control of oocyte quality in cattle “a review”

“…BMP-15 is able to modulate steriodogenesis of granulosa cells (Chang et al, 2013), control the expression of genes implicated in cumulus metabolism (Caixeta et al, 2013) and expansion (Li et al, 2009), and to increase oocyte developmental competence (Hussein et al, 2006). Similarly, GDF-9 enhances cumulus expansion (Gui and Joyce, 2005) and increases oocyte developmental competence (Hussein et al, 2006;Yeo et al, 2008).…”

The role of TGF superfamily gene expression in the regulation of folliculogenesis and oogenesis in mammals: a review

“…However, it is well known that normal mammalian oocyte maturation and development require somatic cumulus cell expansion (CCE) (Jain et al 2012;Barberi et al 2013;Caixeta et al 2013;Gharibi et al 2013;Mito et al 2013). This process is regulated by, among others, paracrine signalling of oocyte-cumulus cell secreted growth factors (Su et al 2009;Romaguera et al 2010;Hussein et al 2011).…”