Introduction: The condition of primary ovarian insufficiency (POI) affects 1% of women worldwide under the age of 40, and is associated with premature ovarian follicle depletion. TAF4b is a gonadal-enriched TFIID subunit that promotes healthy ovarian aging and fertility. Female TAF4b-deficient mice experience POI hallmarks including infertility, poor oocyte quality, and dramatic gene expression changes. Understanding TAF4bs role in promoting healthy ovarian aging is critical for future treatments of POI.
Methods: Immunofluorescence Mouse ovarian sections were fixed with 4% formaldehyde and stained with antibodies against Tra98 and DDX4. They were then incubated with fluorescently-conjugated secondary antibodies for visualization. Neonatal Ovary Culture Wild-type and TAF4b-deficient mouse ovaries were harvested from embryonic-day 18.5 embryos for organ culture until postnatal-day 2. One ovary per mouse was cultured in control media, while the other was cultured in media treated containing ZVAD-fmk or β-estradiol, prior to sectioning and staining.
Results and Discussion: Here we present that TAF4b-deficient ovaries suffer accelerated primordial follicle depletion immediately after birth. This depletion is due to caspase-dependent apoptosis and coincides with delayed cyst nest breakdown. Additionally, germ cell loss in these ovaries can be reduced by culturing embryonic ovaries in the presence of 50 uM pan-caspase inhibitor ZVADFMK or 10 nm β-estradiol, further implicating apoptosis as a primary mechanism for germ cell loss. Furthermore, TAF4b-deficient ovaries experience dramatic ovarian epigenetic deregulation as well as gene expression alterations in meiosis and kinetochore assembly genes, all of which may underlie the observed meiotic defects. This research will help refine our understanding of TAF4bs role in normal ovarian aging.
02 Sep 2014 - 04 Sep 2014