DOI: 10.1101/471698Nov 16, 2018Paper

ATR function is indispensable to allow proper mammalian follicle development.

BioRxiv : the Preprint Server for Biology
Sarai PachecoI Roig

Abstract

Mammalian female fertility relies on the proper development of follicles. Right after birth in mouse, oocytes associate with somatic ovarian cells to form follicles. These follicles grow during adult lifetime to produce viable gametes. In this study, we analyzed the role of the ATM and rad3-related (ATR) kinase in mouse oogenesis and folliculogenesis using a hypomorphic mutation of the Atr gene (Murga et al., 2009). Female mice homozygote for this allele have been reported to be sterile. Our data show that female meiotic prophase is not grossly altered when ATR levels are reduced. However, follicle development is majorly compromised since Atr mutant ovaries present a decrease of growing follicles. Comprehensive analysis of follicular cell death and proliferation suggest that wild-type levels of ATR are required to achieve optimal follicular development. Altogether, these findings suggest that reduced ATR expression causes sterility due to defects in follicular progression rather than in meiotic recombination. We discuss the implication of these findings for the use of ATR inhibitors as anti-cancer drugs and its possible side effects on female fertility.

Related Concepts

Alleles
Antineoplastic Agents
Ataxia Telangiectasia
Birth
Cell Death
Tracheoesophageal Fistula, Esophageal Atresia and Stenosis
Fertility
Laboratory mice
Oocytes
Oogenesis

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