Asymmetric division is a fundamental means of generating cell diversity and may involve extrinsic or intrinsic factors. Here we review observations on symmetric and asymmetric expression of estrogen receptor alpha (ERA) and beta (ERB) during regeneration of trophoblast cells in human placenta and possibly other estrogen-responsive cell types. This is a type of differentiation from committed progenitor cells. Asymmetric segregation of ERA in dividing villous cytotrophoblast cells, accompanied by appearance of ERB in differentiating daughter cells and resulting syncytiotrophoblast, suggests a unique role of estrogen receptors in asymmetric division of estrogen responsive cells. We also review observations on asymmetric division of ovarian surface epithelium (OSE) stem cells resulting in formation of germ cells differentiating into oocytes in fetal and adult human ovaries. Besides germ cells, the OSE stem cells also give rise to primitive ovarian granulosa (follicular) cells, which are required for the formation of new primary follicles and preservation and differentiation of oocytes. This dual potential of OSE stem cells (germ or granulosa cells) is a type of differentiation from uncommitted and possibly totipotent adult stem cells. A possible role of immune system related cells (monocyte-derived cells and T lymphocytes-cellular signaling) and hormones in the stimulation of OSE differentiation toward germ cells by asymmetric division, and in the continuation of ovarian follicular renewal during prime reproductive period in human females is also reviewed. Follicular renewal ceases after prime reproductive period, possibly due to the diminution of cellular signaling required for asymmetric division of OSE stem cells into the germ cells. The primary follicles persisting in premenopausal ovaries appear to accumulate genetic alterations, a cause of exponentially growing chromosomal abnormalities in the progeny of mothers between 38 years of age and menopause.