Fibroblast growth factor 17 and bone morphogenetic protein 15 enhance cumulus expansion and improve quality of in vitro –produced embryos in cattle

Abstract

Bone morphogenetic protein 15 (BMP15) and members of the fibroblast growth factor (FGF) family are expressed by the oocyte and are involved in the control of cumulus cell function. We tested the hypothesis that FGF17, alone or combined with BMP15 in the maturation medium, enhances cumulus expansion, meiosis progression, embryonic development, and expression of mRNA encoding key genes regulating expansion (prostaglandin-endoperoxide synthase 2 [PTGS2], hyaluronan synthase 2 [HAS2], tumor necrosis factor-stimulated gene 6 [TNFAIP6], and pentraxin 3 [PTX3]) and markers of oocyte developmental competence (phosphofructokinase [PFKP], gremlin [GREM1], versican [VCAN], and the genomic progesterone receptor [nPR]) in cumulus cells. Fibroblast growth factor 17 and BMP15 increased the percentage of fully expanded cumulus-oocyte complexes (COCs), but there was no additive effect when both were combined. Neither FGF17 nor BMP15 altered the percentage of oocytes reaching meiosis II at the end of COC culture or cleavage and blastocyst rates after IVF. However, embryo quality, as assessed by the number of cells in the inner cell mass, was improved by the combination of FGF17 with BMP15. Fibroblast growth factor 17 alone did not alter gene expression in cumulus cells at the end of IVM, whereas BMP15 increased PTGS2 and PTX3 mRNA levels. The combination of FGF17 and BMP15 increased nPR mRNA abundance in cumulus cells but did not change the expression of other markers of developmental competence. This study provides novel evidence that FGF17 enhances cumulus expansion in bovine COCs submitted to IVM and that the supplementation of the IVM medium with FGF17 and BMP15 may improve embryo quality.

Mechanisms of fibroblast growth factor signaling in the ovarian follicle

“…FGF17 protein was readily detected in oocytes and granulosa cells; addition of recombinant FGF17 to granulosa cells in vitro inhibited oestradiol and progesterone secretion (Machado et al 2009). Similarly to FGF8, the restricted pattern of expression of FGF17 to the oocyte led to studies of a potential action in cumulus oocyte communication; addition of FGF17 increased the proportion of bovine COCs that fully expanded, but this did not improve the developmental competence of the oocyte (Machado et al 2015).…”

What is the impact of serum and follicular fluid BMP-15 and AMH levels in ICSI-ET cycle outcomes?

“…Researchers observed the enhancing effect of culture medium enriched with BMP-15 on embryo quality in animal studies [10].…”

Follicular environment and oocyte maturation: roles of local peptides and steroids

“…Therefore, additional studies dissecting the influence of species, COC developmental stage and culture conditions are needed for a clearer understanding of the roles of OSF in the regulation of glucose metabolism in the COC. Like FGF10, FGF17 was shown to enhance expansion of bovine COCs during IVM (Machado et al, 2015). However, FGF17 did not alter the expression of PTGS2, or any of the genes in the ovulatory cascade investigated [ADAM10, ADAM17, AREG, EREG, PTX3, TNFAIP6, VERS (versican) and HAS2].…”

“…BMP15 and FGF8 were shown to cooperate to increase the expression and activity of glycolytic enzymes phosphofructokinase (PFKP) and lactate dehydrogenase (LDHA) in cumulus cells from COCs arrested at the germinal vesicle (GV) stage in mice (Sugiura et al, 2007). On the other hand, in bovine COCs undergoing IVM, the combination of BMP15 with FGF17, a member of the FGF8 superfamily also expressed by the bovine oocyte and capable of activating the same receptors that FGF8, did not alter PFKP mRNA levels in cumulus cells (Zhang et al, 2006;Machado et al, 2009Machado et al, , 2015. Therefore, additional studies dissecting the influence of species, COC developmental stage and culture conditions are needed for a clearer understanding of the roles of OSF in the regulation of glucose metabolism in the COC.…”