Accelerated ovarian aging in the absence of the transcription regulator TAF4B in mice.
The mammalian ovary is unique in that its reproductive life span 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 midadult life. If regulation of this pool is perturbed, the reproductive capacity of the ovary is compromised. TAF4B is a gonad-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 female mice 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 16 wk of age. To uncover differences in gene expression that may underlie accelerated ovarian aging, we compared genome-wide expression profiles of 3-wk-old, prepubescent Taf4b-null and wild-type ovaries. At 3 wk of age, decreased gene expression in Taf4b-null ovaries is similar to that 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 posttranscriptional control of ovarian gene expression.
Lovasco
Lindsay A
LA
Department of Molecular and Cell Biology and Biochemistry, Brown University, Providence, Rhode Island 02903, USA.
Seymour
Kimberly A
KA
Zafra
Kathleen
K
O'Brien
Colin W
CW
Schorl
Christoph
C
Freiman
Richard N
RN
D048868:Adaptor Proteins, Signal Transducing / Q000378:metabolism; D000375:Aging / Q000502:physiology*; D000818:Animals; D018797:Cell Cycle Proteins / Q000378:metabolism; D015536:Down-Regulation; D030762:Estrous Cycle; D005260:Female; D038681:Follistatin / Q000378:metabolism; D000071161:Forkhead Box Protein O1; D051858:Forkhead Transcription Factors / Q000378:metabolism; D020869:Gene Expression Profiling; D018398:Homeodomain Proteins / Q000378:metabolism; D007247:Infertility, Female / Q000503:physiopathology; D064246:Mad2 Proteins; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D009687:Nuclear Proteins / Q000378:metabolism; D009865:Oocytes / Q000502:physiology; D010048:Ovarian Cysts / Q000473:pathology; D010053:Ovary / Q000473:pathology / Q000502:physiology*; D051059:PTEN Phosphohydrolase / Q000378:metabolism; D010902:Pituitary Gland / Q000378:metabolism; D051057:Proto-Oncogene Proteins c-akt / Q000378:metabolism; D020365:RNA Helicases / Q000378:metabolism*; D035381:TATA-Binding Protein Associated Factors / Q000378:metabolism*; D035362:Transcription Factor TFIID / Q000378:metabolism*
D048868:Adaptor Proteins, Signal Transducing; D018797:Cell Cycle Proteins; D038681:Follistatin; D000071161:Forkhead Box Protein O1; D051858:Forkhead Transcription Factors; C467200:Foxo1 protein, mouse; D018398:Homeodomain Proteins; D064246:Mad2 Proteins; C577698:Mad2l1 protein, mouse; D009687:Nuclear Proteins; C438001:Smc1l2 protein, mouse; D035381:TATA-Binding Protein Associated Factors; C491103:Taf4b protein, mouse; D035362:Transcription Factor TFIID; D051057:Proto-Oncogene Proteins c-akt; D051059:PTEN Phosphohydrolase; C477006:Mov10l1 protein, mouse; D020365:RNA Helicases
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