TAF4b promotes mouse primordial follicle assembly and oocyte survival.
Primary ovarian insufficiency (POI) affects 1% of women under the age of 40 and is associated with premature ovarian follicle depletion. TAF4b deficiency in adult female mouse models results in hallmarks of POI including stereotyped gonadotropin alterations indicative of early menopause, poor oocyte quality, and infertility. However, the precise developmental mechanisms underlying these adult deficits remain unknown. Here we show that TAF4b is required for the initial establishment of the primordial follicle reserve at birth. Ovaries derived from TAF4b-deficient mice at birth exhibit delayed germ cell cyst breakdown and a significant increase in Activated Caspase 3 staining compared to control ovaries. Culturing neonatal TAF4b-deficient ovaries with the pan-caspase inhibitor ZVAD-FMK suppresses the excessive loss of these oocytes around the time of birth. These data reveal a novel TAF4b function in orchestrating the correct timing of germ cell cyst breakdown and establishment of the primordial follicle reserve during a critical window of development.
Brown University, MCB Graduate Program, Providence, RI, USA.
Kathryn J
KJ
Grive
Brown University, MCB Department, Providence, RI, USA.
Kimberly A
KA
Seymour
Brown University, MCB Department, Providence, RI, USA.
Rajvi
R
Mehta
Brown University, MCB Department, Providence, RI, USA. Electronic address: Richard_Freiman@Brown.edu.
Richard N
RN
Freiman
D000590:Amino Acid Chloromethyl Ketones / Q000494:pharmacology; D000818:Animals; D017209:Apoptosis / Q000187:drug effects; D053148:Caspase 3 / Q000096:biosynthesis / Q000235:genetics; D061945:Caspase Inhibitors / Q000494:pharmacology; D002470:Cell Survival; D047108:Embryonic Development; D004789:Enzyme Activation; D004958:Estradiol / Q000494:pharmacology*; D005260:Female; D051379:Mice; D018345:Mice, Knockout; D009865:Oocytes / Q000166:cytology* / Q000502:physiology; D009866:Oogenesis / Q000235:genetics / Q000502:physiology*; D006080:Ovarian Follicle / Q000196:embryology* / Q000502:physiology; D016649:Primary Ovarian Insufficiency / Q000201:enzymology; D035381:TATA-Binding Protein Associated Factors / Q000235:genetics / Q000378:metabolism*; D035362:Transcription Factor TFIID / Q000235:genetics / Q000378:metabolism*
D000590:Amino Acid Chloromethyl Ketones; D061945:Caspase Inhibitors; D035381:TATA-Binding Protein Associated Factors; C491103:Taf4b protein, mouse; D035362:Transcription Factor TFIID; C096713:benzyloxycarbonylvalyl-alanyl-aspartyl fluoromethyl ketone; D004958:Estradiol; D053148:Caspase 3
Aging; Oocyte survival; Ovary; Primary ovarian insufficiency; Primordial follicle; TFIID