FGF2/FGFR signaling promotes cumulus-oocyte complex maturation in vitro
FGF2/FGFR signaling promotes cumulus-oocyte complex maturation in vitro
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FGF2/FGFR 信号传导促进卵丘-卵母细胞复合物体外成熟
DOI：
10.1530/rep-20-0264
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发表时间：
2021-02-01
期刊：
影响因子：
3.8
通讯作者：
Hua, Guo-Hua
中科院分区：
文献类型：
--
作者：
Du, Chao;Davis, John S.;Hua, Guo-Hua
成纤维细胞生长因子2（Fibroblast growth factor 2，FGF 2）是FGF家族的成员，与FGF受体（FGF receptor，FGFR）结合，启动多种体细胞的生物学功能。然而，关于FGF 2/FGFR在卵母细胞减数分裂中的作用知之甚少。在这项研究中，我们研究了小鼠卵丘-卵母细胞复合体（COCs）体外成熟（IVM）过程中FGF 2/FGFR的表达模式和功能。在四种FGFR中，Ffgr 1在COCs中含量最高。卵母细胞体外成熟过程中Fgf 2和Ffgr 1的转录水平升高。Fggr 1存在于卵母细胞和卵丘细胞中，而Fgf 2仅存在于卵丘细胞中。用选择性FGFR抑制剂SU 5402处理COCs阻断卵母细胞减数分裂进程并下调Brnp 15和Gdf 9的表达。与此相反，FGF 2的补充促进卵母细胞减数分裂进程和上调Bmp 15和Gdf 9的表达。用SU 5402抑制FGFR减少了卵丘扩张和Ptx 3、Has 2和Tnfaip 6的表达。用FGF 2处理增加Ptx 3和Has 2表达。抑制FGFR对裸露卵母细胞（DO）的减数分裂进程没有影响。然而，DO与COC的共培养或补充FGF 2促进了DO的减数分裂进程。抑制FGF 2/FGFR信号传导也下调Ffgr 1表达，而补充FGF 2上调Fgfr 1表达。此外，COCs中FGFR的抑制中断了c-Mos/MAPK通路和促成熟因子（MPF），分别通过下调卵母细胞c-mos和Ccnb 1转录物来表示。总之，本研究表明，卵丘细胞产生的FGF 2激活COCs内的FGF 2/FGFR自分泌/旁分泌回路，从而调节卵丘细胞的扩张和卵母细胞的减数分裂。这些发现揭示了COCs体外成熟过程中FGF 2/FGFR信号转导的新作用。
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 Brnp15 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 su ests 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.