Premature ovarian failure/Primary ovarian insufficiency occurs due to idiopathic causes or following chemotherapy or radiation, and results in the inability of a woman to have her own genetic offspring. Currently, donor eggs from younger women are the only option for these women, given a lack of pharmacologic or surgical treatments to restore ovarian function. Recently, several new stem cell advances have occurred which could be used in future strategies to treat women with premature ovarian aging. Until recently, it was thought that female ovarian germline stem cells (aka ovarian stem cells, oogonial stem cells, OSCs, egg precursor cells, or EggPCs) did not exist. However, these cells have now been isolated in both a murine and human models using magnetic beads and FACS with antibodies against the germ line marker Ddx4 (aka Mouse Vasa Homologue), cultured ex vivo with mitotic expansion, and transplanted in murine and human xenograft models. Adult OSCs were able to enter into meiosis after transplantation back into a donor ovary, where they gave rise to offspring in mice, raising the possibility of therapeutic potential. The goal of this project is to translate technical advances in stem cell research into ways to help women with reproductive disorders. The overall goal of lab is to rapidly translate these reproductive stem cell breakthroughs to clinical trials. However, significant differences in reproductive physiology exist between rodents and primates (e.g. menstrual cycles and hemachorial placentation), which make it critical to perform proof of concept studies in non human primate (NHP) to determine the viability of this approach for future human therapy. As the incidence of infertility rises and women continue to delay reproduction, more fertility preservation options are needed. If this OSC approach is established, all women could bank ovarian stem cells at young ages for later use. This approach would mitigate age related risks of delayed reproduction and provide fertility preservation for unforeseen future idiopathic or iatrogenic premature ovarian failure.
| Hill, Micah J; Levens, Eric D; Wolff, Erin F (2014) Methotrexate for assisted reproductive technology (ART) ectopic pregnancy. Fertil Steril 101:e11 |
