Uterine Cells Improved Ovarian Function in a Murine Model of Ovarian Insufficiency
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Uterine Cells Improved Ovarian Function in a Murine Model of Ovarian Insufficiency
Reproductive Sciences 1-7 ª The Author(s) 2019 Article reuse guidelines: sagepub.com/journals-permissions DOI: 10.1177/1933719119875818 journals.sagepub.com/home/rsx
Andres Reig, MD1, Ramanaiah Mamillapalli, PhD1, Alexis Coolidge, BA1, Joshua Johnson, PhD1, and Hugh S. Taylor, MD1
Abstract Primary ovarian insufficiency (POI) is defined as ovarian dysfunction in women younger than 40 years. It affects 1% of the women in this age-group and can occur iatrogenically after chemotherapy. Stem cells have been used in attempt to restore ovarian function in POI. In particular, endometrial mesenchymal stem cells (eMSCs) are easily obtainable in humans and have shown great potential for regenerative medicine. Here, we studied the potential for uterine cell (UC) suspensions containing eMSCs to improve ovarian function in a murine model of chemotherapy-induced POI. Green fluorescent protein (GFP)-labeled UC or phosphate-buffered solution (PBS) was delivered intravenously after chemotherapy. There was a significant increase in oocytes production and serum anti-Mu¨llerian hormone concentrations after 6 weeks, as well as a 19% higher body mass in UC-treated mice. Similarly, we observed an increased number of pups in mice treated with UC than in mice treated with PBS. None of the oocytes or pups incorporated GFP, suggesting that there was no contribution of these stem cells to the oocyte pool. We conclude that treatment with UC indirectly improved ovarian function in mice with chemotherapy-induced POI. Furthermore, our study suggests that endometrial stem cell therapy may be beneficial to young women who undergo ovotoxic chemotherapy. Keywords primary ovarian insufficiency (POI), uterine cells, endometrial mesenchymal stem cells (eMSCs), ovary, oocytes, AMH, pregnancy, ovarian function, chemotherapy
Introduction Chemotherapy has become a very effective treatment option for women with cancers and autoimmune diseases; while the number and life span of survivors has increased, some of the long-term adverse effects of these therapies has also become evident. Primary ovarian insufficiency (POI)—defined as a loss of ovarian function before the age of 40 years—is a problem affecting up to 1% of women in that age range as a result of chemotherapy, as well as autoimmune, congenital, or endocrine disorders.1 The consequences of POI are similar to those of menopause, including osteoporosis, hot flashes, sexual dysfunction, and infertility.2 In order to address the problem of infertility caused by radiation and chemotherapy, several methods have been developed that protect the ovaries or mitigate the damaging effect of radiation or chemotherapy, including oophoropexy, the use of gonadotropin-releasing hormone (GnRH) agonists, as well as cryopreservation of oocytes embryos or ovarian tissue.3,4 The use of GnRH agonists, which initially showed promise in the preservation of ovarian function, has been demonstrated to be much less effective than originally thoug
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