卵母细胞第一次减数分裂的阻滞和恢复

The first meiotic arrest and resumption in oocytes

哺乳动物卵母细胞第一次减数分裂阻滞期间,来自卵母细胞的Gs-GPR-ADCY诱导环磷酸腺苷(cyclic adenosine monophosphate,cAMP)的生成,升高卵母细胞内cAMP的水平。颗粒细胞中的C型利钠肽(natriuretic peptides C,NPPC)和肌苷-5’-磷酸脱氢酶(inosine-5′-monophosphate dehydrogenase,IMPDH)调节卵丘颗粒细胞中环磷酸鸟苷(cyclic guanosinc monophosphate,cGMP)的生成,cGMP进入卵母细胞抑制cAMP-磷酸二酯酶(cAMP-phosphodiesterase,cAMP-PDE)活性,升高cAMP浓度,并使细胞质成熟促进因子(maturation promoting factor,MPF)处于非活化态,最终诱导了减数分裂阻滞在双线期。促黄体素(luteinizing hormone,LH)峰的出现一方面降低了壁颗粒细胞中NPPC的水平,另一方面激活了卵丘颗粒细胞丝裂原活化蛋白激酶3/1(mitogen-activated protein kinase3/1,MAPK3/1),两者均降低了卵母细胞中cGMP的浓度,促进cAMP水解,使得MPF处于活化态,最终诱导了减数分裂恢复。该综述将探讨这两种环核苷酸如何通过阻断或启动减数分裂过程来调节卵母细胞成熟,并对未来的研究提供一定的见解。

During the first meiotic arrest of mammalian oocytes,the Gs-GPR-ADCY from oocytes stimulates the generation of cyclic adenosine monophosphate(cAMP)and increases cAMP in oocytes.Natriuretic peptide precursor type C(NPPC)and inosine-5’-monophosphate dehydrogenase(IMPDH)produced by granulosa cells stimulate the generation of cyclic guanosinc monophosphate(cGMP),which diffuses into oocytes,inhibits cAMPphosphodiesidase(cAMP-PDE)activity and maintains maturation promoting factor(MPF)as inactive.This inactivation results in the oocytes stop at the diplotene stage.The surge of luteinizing hormone(LH)decreases NPPC levels in mural granulosa cells and activates mitogen-activated protein kinase 3/1(MAPK3/1)in cumulus granulosa cells.Both of them decrease intra-oocyte cGMP level,then result in hydrolyzation of cAMP.The reduction of cAMP ultimately activates oocyte MPF for the successful resumption of the meiosis.This review will discuss how these two cyclic nucleotides regulate oocyte maturation by blocking or initiating meiotic processes,and provide an insight into future research.