TAF4b promotes mouse primordial follicle assembly and oocyte survival

• TAF4b-deficient ovaries contain normal germ cell densities late in embryogenesis.
• TAF4b-deficient mouse ovaries suffer accelerated oocyte depletion at birth.
• TAF4b is required or the proper timing of normal cyst breakdown in the mouse ovary.
• Excessive germ cell loss in TAF4b׳s absence is coincident with Caspase 3 activation.
• Apoptosis inhibition promotes germ cell retention in TAF4b-deficient ovaries.

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.