Premature ovarian failure patient‐specific induced pluripotent stem (iPS) cells show compromised potential to develop to germ cells and granulosa cells

Abstract

Premature ovarian failure (POF), also called primary ovarian insufficiency (POI), is a common endocrine disorder in females, accounting for 1–2% in women during the reproductive ages. Patients with the disease experience spontaneous menopause before the age of 40 years, and frequently encounter significant difficulties and pains in overcoming the problems of infertility and menopausal syndrome. However, the mechanisms underlying POF are difficult to study due to the lack of a suitable disease model. Recently pluripotent stem cells, including human embryonic stem (ES) cells and human induced pluripotent stem (iPS) cells, are becoming useful cell sources to study and dissect the molecular mechanisms underlying in vitro differentiation into specialized cell types. We and other researchers have previously shown that pluripotent stem cells including human ES cells and iPS cells are capable of developing into germ cells and granulosa cells. In this study, we derived POF patient‐specific iPS cell lines from three patients and two controls using skin fibroblasts or PBMCs and induced them to early female germ cells expressing germ cell markers VASA and GDF9 and meiosis marker SCP3, and also to granulosa‐like cells expressing FOXL2, FSHR, AMHR2, AMH and CYP19A1 (aromatase). We observed that the differentiated POF‐patient iPS cells showed differential expression levels of the granulosa cell markers and VASA, when compared to NTU1 human embryonic stem cells. The data demonstrated that iPS cells can be produced from POF patients and control subjects, and these cells can be induced in vitro to early germ cells and granulosa cells, but significantly with compromised potential when compared to other pluripotent stem cells. The POF patient‐specific iPS cells derived in this study thus represent a very useful disease model for further studies to test the disease mechanisms and to test drugs that may be useful for treating POF.Support or Funding InformationNational Science Council of the Republic of China (NSC) and National Taiwan University Hospital (NTUH), Taiwan