FGF2/FGFR signaling promotes cumulus–oocyte complex maturation in vitro

Abstract

Fibroblast growth factor 2 (FGF2), a member of FGF family, binds with FGF receptors (FGFR) to initiate biological functions in various somatic cells. However, little is known regarding the role of FGF2/FGFR on oocyte meiosis. In this study, we investigated expression patterns and functions of FGF2/FGFR during in vitro maturation (IVM) of mouse cumulus-oocyte complexes (COCs). Among four FGFRs, Ffgr1 was the most abundant in COCs. The transcripts for Fgf2 and Ffgr1 in COCs increased during IVM. Ffgr1 was present in oocytes and cumulus cells, while Fgf2 was present in only cumulus cells. Treatment of COCs with the selective FGFR inhibitor SU5402 blocked oocyte meiotic progression and downregulated expression of Bmp15 and Gdf9. In contrast, supplement of FGF2 promoted oocyte meiotic progression and upregulated Bmp15 and Gdf9 expression. Inhibition of FGFR with SU5402 reduced cumulus expansion and expressions of Ptx3, Has2 and Tnfaip6. Treatment with FGF2 increased Ptx3 and Has2 expression. Inhibition of FGFR had no effect on meiotic progression of denuded oocytes (DOs). However, co-culture of DOs with COCs or supplementation with FGF2 promoted meiotic progression of DOs. Inhibition of FGF2/FGFR signaling also downregulated Ffgr1 expression, while supplemental FGF2 upregulated Fgfr1 expression. Furthermore, inhibition of FGFR in COCs interrupted the c-Mos/MAPK pathway and maturation-promoting factor (MPF), as indicated by downregulation of oocyte c-mos and Ccnb1 transcripts, respectively. Overall, this study suggests that FGF2 produced by cumulus cells, activates a FGF2/FGFR autocrine/paracrine loop within COCs to regulate cumulus expansion and oocyte meiosis. These findings reveal a novel role for FGF2/FGFR signaling during in vitro maturation of COCs.

Effect of fibroblast growth factor signaling on cumulus expansion in mice in vitro

“…This suggests that FGF2 exerts suppressive effects on cumulus expansion in cattle. In contrast, in a recent murine study, it was reported that FGF2 promotes cumulus expansion in terms of the degree of expansion and expression of related genes (Du et al, 2021). In addition, the present findings suggest that FGF signals, other than FGF8, exert suppressive effects on the expression of cumulus expansion-related genes in mice.…”

Differential Transcript Profiles in Cumulus-Oocyte Complexes Originating from Pre-Ovulatory Follicles of Varied Physiological Maturity in Beef Cows

“…In cattle, inhibition of FGF signaling on the day of IVF inhibited blastocyst formation, whereas supplementation of FGF2 following IVF increased blastocyst formation [75]. In mice, FGF2 was reported to have an autocrine/paracrine action to promote cumulus expansion and oocyte meiotic maturation [76]. Although FGF 11 expression was more abundant in cumulus cells of large compared to small follicles, FGF 11 is not secreted and its biological function in the cumulus cell/oocyte complex is not currently known [63].…”

Alpha-lipoic acid supplementation restores the meiotic competency and fertilization capacity of porcine oocytes induced by arsenite

“…The cumulus expansion of the COCs and the proportion of PBE are two key indicators of the porcine oocytes developmental competence ( Lan et al, 2020 ; Du et al, 2021 ). Our results revealed that oocytes exhibited a lower proportion of PBE with impaired expansion of cumulus cells following arsenite treatment, indicating that arsenite impairs the oocyte meiotic maturation and developmental competence.…”