4.3 Article

Meiotic Instability Generates a Pathological Condition in Mammalian Ovum

Journal

STEM CELL REVIEWS AND REPORTS
Volume 17, Issue 3, Pages 777-784

Publisher

SPRINGER
DOI: 10.1007/s12015-020-10072-z

Keywords

ROS; Calcium; MPF destabilization; Meiotic instability, abortive SOA; Mammals

Funding

  1. Department of Biotechnology, Ministry of Science and Technology, Government of India [BT/PR4225/AAQ/1/492/2011]

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Meiotic instability leads to abortive spontaneous ovum activation (SOA), affecting egg quality and fertilization outcomes. Signal molecules such as ROS, cAMP, and Ca2+ are involved in the induction of meiotic instability. Global attention is needed to identify and address meiotic instability in ova, with potential use of activated ova in regenerative medicine.
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.

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