Maintenance of metaphase-II (M-II) arrest in ovum is required to present itself as a right gamete for successful fertilization in mammals. Surprisingly, instability of meiotic cell cycle results in spontaneous exit from M-II arrest, chromosomal scattering and incomplete extrusion of second polar body (PB-II) without forming pronuclei so called abortive spontaneous ovum activation (SOA). It remains unclear what causes meiotic instability in freshly ovulated ovum that results in abortive SOA. We propose the involvement of various signal molecules such as reactive oxygen species (ROS), cyclic 3′,5′ adenosine monophosphate (cAMP) and calcium (Ca²⁺) in the induction of meiotic instability and thereby abortive SOA. These signal molecules through their downstream pathways modulate phosphorylation status and activity of cyclin dependent kinase (cdk1) as well as cyclin B1 level. Changes in phosphorylation status of cdk1 and its activity, dissociation and degradation of cyclin B1 destabilize maturation promoting factor (MPF). The premature MPF destabilization and defects in other cell cycle regulators possibly cause meiotic instability in ovum soon after ovulation. The meiotic instability results in a pathological condition of abortive SOA and deteriorates ovum quality. These ova are unfit for fertilization and limit reproductive outcome in several mammalian species including human. Therefore, global attention is required to identify the underlying causes in greater details in order to address the problem of meiotic instability in ova of several mammalian species icluding human. Moreover, these activated ova may be used to create parthenogenetic embryonic stem cell lines in vitro for the use in regenerative medicine.

Graphical abstract

维持卵子中的中期 II (M-II) 停滞是哺乳动物成功受精的正确配子所必需的。令人惊讶的是，减数分裂细胞周期的不稳定性导致自发退出 M-II 停滞、染色体散射和第二极体 (PB-II) 的不完全挤出，而不形成所谓的原核自发性卵子激活 (SOA)。目前尚不清楚是什么原因导致新鲜排卵的卵子减数分裂不稳定，从而导致 SOA 流产。我们建议参与各种信号分子，例如活性氧 (ROS)、环状 3',5' 腺苷一磷酸 (cAMP) 和钙 (Ca ²⁺) 诱导减数分裂不稳定性，从而导致 SOA 失败。这些信号分子通过其下游途径调节磷酸化状态和细胞周期蛋白依赖性激酶 (cdk1) 的活性以及细胞周期蛋白 B1 水平。cdk1 磷酸化状态的变化及其活性、细胞周期蛋白 B1 的解离和降解使成熟促进因子 (MPF) 不稳定。过早的 MPF 不稳定和其他细胞周期调节剂的缺陷可能导致排卵后不久卵子的减数分裂不稳定。减数分裂不稳定性导致流产 SOA 的病理状态并恶化卵子质量。这些卵子不适合受精，并限制了包括人类在内的几种哺乳动物的生殖结果。所以，需要全球关注以更详细地确定根本原因，以解决包括人类在内的几种哺乳动物的卵子减数分裂不稳定的问题。此外，这些活化的卵子可用于在体外产生孤雌胚胎干细胞系，用于再生医学。

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