Ovarian granulosa cell survival and proliferation requires the gonad-selective TFIID subunit TAF4b

Abstract

Oocyte development in the mammalian ovary requires productive interactions with somatic granulosa cells of the ovarian follicle. Proliferating granulosa cells support the progression of follicular growth and maturation, multiplying dramatically as it unfolds. The cell cycle recruitment of granulosa cells is regulated at least in part by hormones such as follicle-stimulating hormone (FSH) and estrogen. Follicles recruited into the growth phase following formation of multiple layers of granulosa cells have two major fates: either to continue proliferation followed by differentiation, or to die by programmed cell death, or atresia. While many of the signaling pathways orchestrating ovarian follicle development are known, the downstream transcriptional regulators that integrate such signals in the mammalian ovary remain to be defined. Recent experiments in diverse organisms have revealed multiple instances of gonad-selective components of the basal transcriptional machinery. One such protein, TAF4b, is a gonadal-enriched coactivator subunit of the TFIID complex required for normal female fertility in the mouse. To determine the etiology of female infertility of the TAF4b-deficient mice, we have determined multiple functions of TAF4b during postnatal ovarian follicle development. Here we demonstrate that the TAF4b protein is expressed in the granulosa cell compartment of the mammalian ovarian follicle. Furthermore, TAF4b-deficient mouse ovaries contain reduced numbers of primordial as well as growing follicles and a concomitant increased proportion of apoptotic follicles in comparison to wild type counterparts. Importantly, TAF4b-null follicles are largely resistant to induction of proliferation in response to multiple hormonal stimuli including estrogen and FSH and demonstrate compromised granulosa cell survival. Together, these data suggest that TAF4b integrates a program of granulosa cell gene expression required for normal ovarian follicle survival and proliferation in response to diverse ovarian signaling events.

The developmental origins of the mammalian ovarian reserve

“…One of the best-characterized selective subunits of the general transcriptional complex TFIID is TBP-associated factor 4b (TAF4b), a paralog of TAF4, originally identified in a human B-cell line and found to be primarily enriched in the mouse ovary and testis (Freiman et al, 2001). Taf4b-deficient female mice are viable but infertile and suffer from many hallmarks of premature ovarian failure, including follicle depletion, persistent estrous and high serum levels of the gonadotropin follicle stimulating hormone (FSH) (Falender et al, 2005;Freiman et al, 2001;Lovasco et al, 2010;Voronina et al, 2007). Recent work has demonstrated that Taf4b-deficient ovaries experience dramatic germ cell loss by apoptosis immediately after birth, the time at which the ovarian reserve is established (Grive et al, 2014).…”

“…Impaired cyst breakdown; loss of primordial follicles (Lechowska et al, 2011;Rajkovic et al, 2004;Suzumori et al, 2002) TBP-associated Factor 4b (Taf4b) Impaired cyst breakdown; loss of primordial follicles (Falender et al, 2005;Freiman et al, 2001;Grive et al, 2014;Lovasco et al, 2010;Voronina et al, 2007) …”

MOV10L1 in piRNA processing and gene silencing of retrotransposons during spermatogenesis

“…To date, not any correlation studies can explain that the Mov10l1 K/K mice is still fertile. In female mice, TAF4B is a gonad-enriched subunit of the TFIID complex required for fertility (Voronina et al 2007). Lovasco et al reported the development of premature reproductive senescence in young Taf4b-null female mice.…”

Novel Serum Biomarkers Detected by Protein Array in Polycystic Ovary Syndrome with Low Progesterone Level

“…The inhibition of granulosa cells proliferation leads to the impairment of follicle development, as well as follicular atresia and even ovulation disorder [13]. Furthermore, this process is also accompanied by changes in many molecules, like cytokines, growth factors and adhesion molecules.…”