Insights into Primary Ovarian Insufficiency through Genetically Engineered Mouse Models

ABSTRACT

Primary ovarian insufficiency (POI), also known as premature ovarian failure, is a form of hypergonadotropic hypogonadism that causes infertility in ~1% of women <40 years of age. POI has important health consequences for affected patients; however, the mechanisms that cause ovarian dysfunction are poorly understood. Elucidating these mechanisms is paramount to developing better testing and treatment strategies for affected girls and women. For obvious reasons, studies looking directly at the human ovary are extremely limited. Recently, numerous genetically engineered mouse models have been developed to investigate the molecular mechanisms that may be involved in the pathogenesis of POI. Two potential mechanisms may be involved in the development of POI: (1) abnormalities in primordial follicle activation and (2) increased rates of apoptosis of oocytes. Each of these mechanisms may lead to early depletion of ovarian follicular reserve, and thus be a contributing factor in POI. This review addresses current knowledge of molecular mechanisms controlling primordial follicle activation and oocyte apoptosis, as evidenced from various genetic mouse models. Translation of these data into clinically effective treatments or even prevention strategies may improve fertility and quality of life for women with this form of reproductive dysfunction.

KEYWORDS

Primary ovarian insufficiency - premature ovarian failure - primordial follicle activation - apoptosis - mouse model

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1 Current affiliation: Washington Hospital Center, Department of Endocrinology, Washington, D.C.