Transcriptional Integration of Meiotic Prophase I Progression and Early Oocyte Differentiation

Female reproductive senescence results from the regulated depletion of a finite pool of oocytes called the ovarian reserve. This pool of oocytes is initially established during fetal development, but the oocytes that comprise it must remain quiescent for decades until they are activated during maturation in adulthood. In order for developmentally competent oocytes to populate the ovarian reserve they must successfully initiate both meiosis and oogenesis. As the factors that regulate the timing and fidelity of these early events remain elusive, we assessed the precise function and timing of the transcriptional regulator TAF4b during meiotic prophase I progression in mouse fetal oocytes. Compared to matched controls, E14.5 Taf4b-deficient oocytes enter meiosis I in a timely manner however, their subsequent progression through the pachytene-to-diplotene transition of meiotic prophase I is compromised. Moreover, this disruption of meiotic progression is associated with the reduced ability of Taf4b-deficient oocytes to repair double-strand DNA breaks. Transcriptional profiling of Taf4b-deficient oocytes reveals that between E16.5 and E18.5 these oocytes fail to coordinate the reduction of meiotic gene expression and the induction of oocyte differentiation genes. These studies reveal that TAF4b promotes the formation of the ovarian reserve in part by orchestrating the timely transition to meiosis I arrest and oocyte differentiation, which are often perceived as separate events.