Oogenesis from Human Somatic Stem Cells and a Role of Immune Adaptation in Premature Ovarian Failure

The central thesis is that, while embryonic oocytes originate from extra-ovarian sources, those generated during fetal period and in postnatal life are derived from the ovarian surface epithelium (OSE). With the assistance of immune system-related cells, primitive granulosa and germ cells appear to originate from OSE stem cells in the fetal and adult human gonads. Fetal primary follicles are formed during the second trimester of intrauterine life, prior to the end of immune adaptation, possibly in order to be recognized as self and renewed later. With the onset of menarche, a periodical follicular renewal emerges to replace aging primary follicles and ensure that fresh eggs are always available during the prime reproductive period. The periodical follicular renewal ceases between 35-40 years of age, and the remaining primary follicles are utilized during the premenopausal period until exhausted. However, the persisting oocytes accumulate genetic alterations and may become unsuitable for ovulation and fertilization. Premature ovarian failure (POF) may result from premature termination of follicular renewal during adulthood, possibly due to the alteration of fetal follicular development during immune adaptation (idiopathic POF), or due to the alteration of the adult immune system by cytostatic chemotherapy. Factors responsible for the diminution of follicular renewal may be responsible for the aging of other tissues and the whole body in general. However, our recent research shows that OSE stem cells may produce new eggs in vitro, even when derived from ovaries lacking primary follicles. Consequently, their in vitro fertilization (IVF) and subsequent utilization of embryos for intrauterine implantation may represent a novel IVF approach for providing genetically related children to women with ovarian infertility, which is worthy of consideration and further exploration.