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Accelerated Ovarian Aging in the Absence of the Transcription Regulator TAF4B in Mice. Lovasco LA et al. The mammalian ovary is unique in that its reproductive lifespan is limited by oocyte quantity and quality. Oocytes are recruited from a finite pool of primordial follicles that are usually exhausted from the ovary during mid-adult life. If regulation of this pool is perturbed, the reproductive capacity of the ovary is compromised. TAF4B is a gonadal-enriched subunit of the TFIID complex required for female fertility in mice. Previous characterization of TAF4B-deficient ovaries revealed several reproductive deficits that collectively result in infertility. However, the etiology of such fertility defects remains unknown. By assaying estrous cycle, ovarian pathology and gene expression changes in young Taf4b-null female mice, we show that TAF4B-deficient females exhibit premature reproductive senescence. The rapid decline of ovarian function in Taf4b-null mice begins in early postnatal life and follicle depletion is completed by sixteen weeks. To uncover differences in gene expression that may underlie accelerated ovarian aging, we compared genome-wide expression profiles of three week old, pre-pubescent Taf4b-null and wildtype ovaries. At three weeks of age, decreased gene expression in Taf4b-null ovaries is similar to those seen in aged ovaries revealing several molecular signatures of premature reproductive senescence, including reduced Smc1b. One significantly reduced transcript in the young TAF4B-null ovary codes for MOV10L1, a putative germline-specific RNA helicase that is related to the Drosophila RNA interference protein armitage. We show here that Mov10l1 is expressed in mouse oocytes and that its expression is sensitive to TAF4B level, linking TAF4B to the post-transcriptional control of ovarian gene expression.
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