Abstract
DNA damage in oocytes can cause infertility and birth defects. DNA double-strand breaks (DSBs) are highly deleterious and can substantially impair genome integrity. Homologous recombination (HR)-mediated DNA DSB repair plays dominant roles in safeguarding oocyte quantity and quality. However, little is known regarding the key players of the HR repair pathway in oocytes. Here, we identified oocyte-specific gene Ooep as a novel key component of the HR repair pathway in mouse oocytes. OOEP was required for efficient ataxia telangiectasia mutated (ATM) kinase activation and Rad51 recombinase (RAD51) focal accumulation at DNA DSBs. Ooep null oocytes were defective in DNA DSB repair and prone to apoptosis upon exogenous DNA damage insults. Moreover, Ooep null oocytes exhibited delayed meiotic maturation. Therefore, OOEP played roles in preserving oocyte quantity and quality by maintaining genome stability. Ooep expression decreased with the advance of maternal age, suggesting its involvement in maternal aging.
Highlights
During the long period of meiotic arrest, oocytes are exposed to endogenous and exogenous genotoxic insults and tend to accumulate DNA damage
Ooep participates in DNA double-strand break repair in mouse oocytes Upon DNA damage, histone H2AX is phosphorylated at Ser139 (γ-H2AX) and recruited to the damaged sites to form visible foci under confocal microscopy (Rogakou et al, 1998). γ-H2AX foci formation is generally considered as a marker of DNA damage
We investigated the influence of OOEP loss on the kinetics of germinal vesicle breakdown (GVBD) and the first polar body extrusion (PBE) during oocyte in vitro maturation
Summary
During the long period of meiotic arrest, oocytes are exposed to endogenous and exogenous genotoxic insults and tend to accumulate DNA damage. DNA damage can occur as single-stranded breaks (SSBs) or double-strand breaks (DSBs), the latter of which are highly deleterious and can substantially impair genomic integrity and cell viability. Two major pathways are involved in DNA DSB repair, non-homologous end joining (NHEJ)- and homologous recombination (HR)-mediated repair. HR-based DNA DSB repair in oocytes plays a key role in regulating female reproductive performance. This repair has been intensively studied in somatic cells, with many players identified (Adamson et al, 2012); little information is available regarding the components of the HR repair pathway in oocytes. Identifying essential participants will shed light on understanding oocyte and ovarian aging
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