Human eggs can develop from ovarian surface cells in vitro

Research has shown for the first time that human eggs may develop directly from cultured ovarian surface epithelium (OSE) cells derived from adult human ovaries. Oocytes derived from the culture of OSE cells developed in vitro into mature eggs suitable for fertilization and development into an embryo. These findings, published today in the Open Access journal Reproductive Biology and Endocrinology, offer important new strategies for use in in vitro fertilization and stem cell research, and cast doubt on the established dogma on the fetal origin of eggs in adult human ovaries.

It is now well established that fetal mammalian eggs originate from somatic stem cells. More recent research of adult human ovaries has shown that oocytes and granulosa cells (the layer of small cells that form the wall of the ovarian follicle) may originate from OSE cells and assemble together to form new primary follicles – the structures that grow and rupture during ovulation to release mature eggs. However, definitive proof that new oocytes may develop in adult human females will be if they can be found to differentiate in vitro from OSE cells derived from adult human ovaries.

For the first time, Antonin Bukovsky and colleagues from the Department of Obstetrics and Gynecology of the University of Tennessee, United States, have shown that human eggs and granulosa cells) can develop from cultured OSE cells. By scraping cells from the surface of adult ovaries and growing them for 5 to 6 days in the presence of an estrogen-containing medium (phenol red) to stimulate their growth, the team was able to produce new human oocytes in vitro.

The oocytes cultured in this way are viable and went on to successfully complete the first meiotic division to become mature human eggs – capable of being fertilized and developing into an embryo. These in vitro findings support earlier in vivo studies by Bukovsky and colleagues that OSE cells are bipotent; capable of differentiating along two developmental pathways and becoming either egg or granulosa cells. The authors speculate that this bipotent differentiation may represent a sophisticated mechanism created during the evolution of female reproduction, and not seen in ovaries of female prosimians (ancestral primates) or mice carrying germline stem cells.

The ability to produce mature human eggs from adult ovaries in vitro has several potential applications in human reproduction. The technique of harvesting cells from the ovarian surface is relatively easy, can be accomplished by a laparoscopy technique, and yields more cells for use for in vitro fertilization. The ability to develop human eggs from OSE cells may help women with reduced fertility and premature menopause, who lack follicles in their ovaries, to have a better chance of conceiving through in vitro fertilization. Eventually, frozen OSE cells from younger females may be preserved for later production of fresh eggs. This may prevent the occurrence of fetal genetic alterations, which are often associated with an advanced maternal age. In addition, a colonization of premenopausal ovaries with younger oocyte and granulosa stem cells may establish a new cohort of primary follicles. This may result in a 10- to 12-year delay of the onset of natural menopause. Also, these ovarian stem cells could be used to generate several cell types used in stem cell research, and fertilized eggs produced in this way could produce cells capable of giving rise to embryonic stem cells for use in research and therapeutic applications.