Interference with the C-terminal structure of MARF1 causes defective oocyte meiotic division and female infertility in mice

Abstract

Meiosis-arrest female 1 (MARF1) is a recently identified key oogenic regulator essential for the maintenance of female fertility and genome integrity in mice. However, the detailed functions and the underlying mechanisms of MARF1 remain elusive. Here, in an attempt to create a mouse model expressing fluorescent protein-tagged MARF1 to facilitate further exploration of the roles of MARF1 in oocytes, we produced a Marf1-eGFP knockin (KI) mouse line in which the C-terminal structure and function of MARF1 were interfered by its fusing eGFP peptide. Using these Marf1-eGFP-KI mice, we revealed, unexpectedly, the functions of MARF1 in the control of oocyte meiotic division. We found that the Marf1-eGFP-KI females ovulated mature oocytes with severe meiotic and developmental defects, and thus were infertile. Moreover, meiotic reinitiation was delayed while meiotic completion was accelerated in the KI-oocytes, which was coincident with the increased incidence of oocyte aneuploidy. Therefore, MARF1 is indispensable for maintaining the fidelity of homolog segregation during oocyte maturation, and this function relies on its C-terminal domains.

Keywords

MARF1 / meiosis / oocyte aneuploidy / female infertility / knock in / CRISPER/Cas9

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Acknowledgments

This study was supported by National Basic Research Program (973) from Ministry of Science and Technology of the People’s Republic of China (grant numbers 2014CB943200, 2013CB945500); National Natural Science Foundation of China (grant numbers 31471351, 31271538); Natural Science Foundation of Jiangsu Province (grant number BK20140061) to YQ Su.

RIGHTS & PERMISSIONS

2018 2018 by the Journal of Biomedical Research.