Fertility & Research Centre, School of Women's & Children's Health, University of New South Wales Sydney, NSW, Australia.
Biol Reprod. 2022 Feb 22;106(2):243-252. doi: 10.1093/biolre/ioab176.
Oocytes are maintained in a state of meiotic arrest following the first meiotic division until ovulation is triggered. Within the antral follicle, meiotic arrest is actively suppressed in a process facilitated by the cyclic nucleotides cGMP and cAMP. If removed from this inhibitory follicular environment and cultured in vitro, mammalian oocytes undergo spontaneous meiotic resumption in the absence of the usual stimulatory follicular stimuli, leading to asynchronicity with oocyte cytoplasmic maturation and lower developmental competence. For more than 50 years, pharmacological agents have been used to attenuate oocyte germinal vesicle (GV) breakdown in vitro. Agents that increase intra-oocyte cAMP or prevent its degradation have been predominantly used; however, agents such as kinase and protein synthesis inhibitors have also been trialed. Twenty years of research demonstrates that maintaining GV arrest for a period before in vitro maturation (IVM) improves oocyte developmental competence, and is likely attributed to maintenance of bidirectional communication with cumulus cells leading to improved oocyte metabolic function. However, outcomes are influenced by various factors including the mode of action of the modulators, dose, treatment duration, species, and the degree of hormonal priming of the oocyte donor. Cyclic GMP and/or cAMP modulation in a prematuration step (called pre-IVM) prior to IVM has shown the greatest consistency in improving oocyte developmental competence, whereas kinase and protein synthesis inhibitors have proven less effective at improving IVM outcomes. Such pre-IVM approaches have shown potential to alter current use of artificial reproductive technologies in medical and veterinary practice.
卵母细胞在第一次减数分裂后处于减数分裂阻滞状态，直到排卵被触发。在窦卵泡内，减数分裂阻滞在由环核苷酸 cGMP 和 cAMP 介导的过程中被主动抑制。如果将其从抑制性卵泡环境中取出并在体外培养，哺乳动物卵母细胞会在没有通常的卵泡刺激物的情况下自发恢复减数分裂，导致与卵母细胞细胞质成熟的不同步和较低的发育能力。五十多年来，人们一直使用药理学制剂来减弱卵母细胞生发泡（GV）在体外的破裂。主要使用增加卵内 cAMP 或防止其降解的制剂；然而，也已经尝试了激酶和蛋白质合成抑制剂等制剂。二十年的研究表明，在体外成熟（IVM）之前维持 GV 阻滞一段时间可以提高卵母细胞的发育能力，这可能归因于与卵丘细胞保持双向通讯，从而改善卵母细胞的代谢功能。然而，结果受到多种因素的影响，包括调节剂的作用方式、剂量、治疗持续时间、物种以及卵母细胞供体的激素预刺激程度。在 IVM 之前的预成熟阶段（称为预-IVM）中对 cGMP 和/或 cAMP 进行调节，在提高卵母细胞发育能力方面显示出最大的一致性，而激酶和蛋白质合成抑制剂在改善 IVM 结果方面效果较差。这种预-IVM 方法有可能改变当前在医学和兽医实践中对人工生殖技术的使用。
