Prospects of Primary Ovarian Insufficiency Patient-Specific Pluripotent Stem Cells for Disease Modeling and Clinical Impacts

Background: Primary ovarian insufficiency (POI) or premature ovarian failure (POF) is defined by spontaneous amenorrhea with elevated serum gonadotropin levels and reduced estradiol level. POI frequently leads to reduced fertility and a number of clinical symptoms or signs related to premature menopause. The etiologies of POI include genetic or chromosomal defects, autoimmune factors, environmental factors, and idiopathic causes. However, the pathogenesis of POI is difficult to study due to a lack of suitable disease models. Recent evidence suggests that pluripotent stem cells (PSCs), including embryonic stem (ES) cells and induced pluripotent stem (iPS) cells, can be induced into germ cells and granulosa cells. Specifically, mouse PSCs can be directed to functional sperm and oocytes that lead to viable and fertile offspring. However, in humans, only early germ cells have been derived, including female primordial germ cells and immature haploid male germ cells with meiotic potential. Some evidence also suggests defective differentiation potential into germ cells and granulosa cells from POI patient-specific iPS cells (by reprogramming somatic cells from POI patients).

Objective and Results: This report reviews current studies, advances, and future prospects in the derivation of POI patient-specific iPS cells, the efficiency of differentiating iPS cells into functional and mature germ cells and granulosa cells, and the potential to use the entire process as a disease model to screen drugs, toxicants and toxins.

Conclusion: It is concluded that current data have provided good evidence to support the use of POI patient-specific iPS cells to model human POI and potentially other reproductive disorders.