Oocyte Quality Control: Causes, Mechanisms, and Consequences.

Abstract

Oocyte quality and number are key determinants of reproductive life span and success. These variables are shaped in part by the elimination of oocytes that experience problems during the early stages of meiosis. Meiotic prophase-I marks an extended period of genome vulnerability in which epigenetic reprogramming unleashes retroelements and hundreds of DNA double-strand breaks (DSBs) are inflicted to initiate the programmed recombination required for accurate chromosome segregation at the first meiotic division. Expression of LINE-1 retroelements perturbs several aspects of meiotic prophase and is associated with oocyte death during the early stages of meiotic prophase I. Defects in chromosome synapsis and recombination also trigger oocyte loss, but typically at a later stage, as cells transition into quiescence and form primordial follicles. Interrelated pathways that signal defects in DSB repair and chromosome synapsis mediate this late oocyte attrition. Here, I review our current understanding of early and late oocyte attrition based on studies in mouse and describe how these processes appear to be both distinct and overlapping and how they help balance the quality and size of oocyte reserves to maximize fecundity.