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bioRxiv · 10.1101/656645

Evading non-essential fetal oocyte attrition maximizes the ovarian reserve

Tharp, M. E.·Malki, S.·Bortvin, A.
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Abstract

Female reproductive success depends on the size and quality of a finite ovarian reserve. Paradoxically, mammals such as mice and humans eliminate up to 80% of the initial oocyte pool during development through the enigmatic process of fetal oocyte attrition (FOA). Here we report that the combined inhibition of retrotransposon L1 reverse transcriptase and the Chk2-dependent DNA damage checkpoint prevents FOA, thus preserving the entire fetal oocyte population. Remarkably, reverse transcriptase inhibitor AZT-treated Chk2 mutant oocytes initially accumulate, but subsequently resolve L1-instigated genotoxic threats and differentiate, resulting in a maximized functional ovarian reserve. We conclude that FOA is a consequence of genotoxic stress that acts to preserve oocyte genome integrity, and is not an obligatory developmental program for oogenesis.

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Tharp, M. E., Malki, S., Bortvin, A.. 2019-06-03. Evading non-essential fetal oocyte attrition maximizes the ovarian reserve. https://doi.org/10.1101/656645

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