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成熟促进因子的失稳介导人绒毛膜促性腺激素诱导大鼠卵母细胞减数分裂恢复。

Maturation promoting factor destabilization mediates human chorionic gonadotropin induced meiotic resumption in rat oocytes.

作者信息

Tiwari Meenakshi, Chaube Shail K

机构信息

Cell Physiology Laboratory, Department of Zoology, Institute of Science, Banaras Hindu University, Varanasi, 221005, U.P., India.

出版信息

Dev Growth Differ. 2017 Sep;59(7):603-614. doi: 10.1111/dgd.12387. Epub 2017 Aug 16.

Abstract

Human chorionic gonadotropin (hCG) mimics the action of luteinizing hormone (LH) and triggers meiotic maturation and ovulation in mammals. The mechanism by which hCG triggers meiotic resumption in mammalian oocytes remains poorly understood. We aimed to find out the impact of hCG surge on morphological changes, adenosine 3',5'-cyclic monophosphate (cAMP), guanosine 3',5'-cyclic monophosphate (cGMP), cell division cycle 25B (Cdc25B), Wee1, early mitotic inhibitor 2 (Emi2), anaphase-promoting complex/cyclosome (APC/C), meiotic arrest deficient protein 2 (MAD2), phosphorylation status of cyclin-dependent kinase 1 (Cdk1), its activity and cyclin B1 expression levels during meiotic resumption from diplotene as well as metaphase-II (M-II) arrest in cumulus oocyte complexes (COCs). Our data suggest that hCG surge increased cyclic nucleotides level in encircling granulosa cells but decreased their level in oocyte. The reduced intraoocyte cyclic nucleotides level is associated with the decrease of Cdc25B, Thr161 phosphorylated Cdk1 and Emi2 expression levels. On the other hand, hCG surge increased Wee1, Thr14/Tyr15 phosphorylated Cdk1, APC/C as well as MAD2 expression levels. The elevated APC/C activity reduced cyclin B1 level. The changes in phosphorylation status of Cdk1 and reduced cyclin B1 level might have resulted in maturation promoting factor (MPF) destabilization. The destabilized MPF finally triggered resumption of meiosis from diplotene as well as M-II arrest in rat oocytes.

摘要

人绒毛膜促性腺激素(hCG)模拟促黄体生成素(LH)的作用,并触发哺乳动物的减数分裂成熟和排卵。hCG触发哺乳动物卵母细胞减数分裂恢复的机制仍知之甚少。我们旨在研究hCG激增对卵丘卵母细胞复合体(COC)从双线期以及中期II(M-II)阻滞恢复减数分裂过程中形态变化、3',5'-环磷酸腺苷(cAMP)、3',5'-环磷酸鸟苷(cGMP)、细胞分裂周期25B(Cdc25B)、Wee1、早期有丝分裂抑制剂2(Emi2)、后期促进复合体/环体(APC/C)、减数分裂阻滞缺陷蛋白2(MAD2)、细胞周期蛋白依赖性激酶1(Cdk1)的磷酸化状态、其活性和细胞周期蛋白B1表达水平的影响。我们的数据表明,hCG激增会增加包围颗粒细胞中的环核苷酸水平,但会降低卵母细胞中的环核苷酸水平。卵母细胞内环核苷酸水平的降低与Cdc25B、苏氨酸16(Thr16)磷酸化的Cdk1和Emi2表达水平的降低有关。另一方面,hCG激增会增加Wee1、苏氨酸14/酪氨酸15(Thr14/Tyr15)磷酸化的Cdk1、APC/C以及MAD2的表达水平。升高的APC/C活性会降低细胞周期蛋白B1的水平。Cdk1磷酸化状态的变化和细胞周期蛋白B1水平的降低可能导致成熟促进因子(MPF)不稳定。不稳定的MPF最终触发大鼠卵母细胞从双线期以及M-II阻滞恢复减数分裂。

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