Defective Gonadotropin-Dependent Ovarian Folliculogenesis and Granulosa Cell Gene Expression in Inhibin-Deficient Mice

Department of Pathology and Immunology, Baylor College of Medicine, One Baylor Plaza, Houston, Texas 77030, USA.
Endocrinology (Impact Factor: 4.5). 10/2010; 151(10):4994-5006. DOI: 10.1210/en.2010-0428
Source: PubMed


Inhibin-α knockout (Inha-/-) female mice develop sex cord-stromal ovarian cancer with complete penetrance and previous studies demonstrate that the pituitary gonadotropins (FSH and LH) are influential modifiers of granulosa cell tumor development and progression in inhibin-deficient females. Recent studies have demonstrated that Inha-/- ovarian follicles develop precociously to the early antral stage in prepubertal mice without any increase in serum FSH. These studies suggest that in the absence of inhibins, granulosa cells differentiate abnormally and thus at sexual maturity may undergo an abnormal response to gonadotropin signaling contributing to tumor development. To test this hypothesis, we stimulated immature wild-type and Inha-/- female mice with gonadotropin analogs prior to tumor formation and subsequently examined gonadotropin-induced ovarian follicle development as well as preovulatory and human chorionic gonadotropin-induced gene expression changes in granulosa cells. We find that at 3 wk of age, inhibin-deficient ovaries do not show further antral development or undergo cumulus expansion. In addition, there are widespread alterations in the transcriptome of gonadotropin-treated Inha-/- granulosa cells, with significant changes in genes involved in extracellular matrix and cell-cell communication. These data indicate the gonadotropins initiate an improper program of cell differentiation prior to tumor formation in the absence of inhibins.

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Available from: Stephanie Pangas, Apr 17, 2014
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    • "Genes belonging to TGFB superfamily are important regulators; they are called also “checkpoints of oocyte maturation potential" [23]. INHA and INHB are members of TGFB superfamily and it is suggested that they regulate important stages of oocyte maturation in vivo and in vitro [24–26]. However, the influence of several factors, for example, the follicular size and/or in vitro cultivation, on INHA and INHB mRNA expression profile or encoded proteins distribution within the porcine oocytes, is still not entirely known. "
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