Human Mesenchymal Stem Cells Partially Reverse Infertility in Chemotherapy-Induced Ovarian Failure

• Published in: Reproductive sciences (Thousand Oaks, Calif.) Calif.), 2018-01, Vol.25 (1), p.51-63
• Main Authors: Mohamed, Sara A., Shalaby, Shahinaz M., Abdelaziz, Mohamed, Brakta, Soumia, Hill, William D., Ismail, Nahed, Al-Hendy, Ayman
• Format: Article
• Language: English
• Subjects: Animals; Antineoplastic Agents - adverse effects; Bone Marrow Cells; Busulfan - adverse effects; Cyclophosphamide - adverse effects; Embryology; Female; Humans; Medicine & Public Health; Mesenchymal Stem Cell Transplantation; Mice; Obstetrics/Perinatology/Midwifery; Original; Original Article; Primary Ovarian Insufficiency - chemically induced; Primary Ovarian Insufficiency - therapy; Reproductive Medicine; Treatment Outcome
• ISSN: 1933-7191; 1933-7205
• DOI: 10.1177/1933719117699705

Introduction: Chemotherapy is the most commonly used modality to treat human cancers; however, in many cases it causes irreversible ovarian failure. In this work, we plan to evaluate the restorative function of human bone marrow mesenchymal stem cells (BMSCs) in a chemotherapy-induced ovarian failure mouse model. Methods: Acclimatized 4 to 6 week-old female mice (C57BL/6) were assigned randomly to a vehicle-treated control group (group 1), chemotherapy-treated group followed by vehicle alone (group 2), or chemotherapy-treated group followed by stem cell intraovarian injection (group 3). Outcomes were evaluated using immunohistochemistry (IHC), serum hormonal assays, and estrous cycle monitoring and breeding potential. Results: Post BMSCs administration, group 3 promptly showed detectable vaginal smears with estrogenic changes. Increase in total body weight, ovarian weight, and weight of estrogen-responsive organs (uterus and liver) was observed at 2 weeks and continued to end of the experiment. Hematoxylin and Eosin histological evaluation of the ovaries demonstrated a higher mean follicle count in group 3 than in group 2. Group 3 had lower follicle-stimulating hormone (FSH) levels (P = .03) and higher anti-Müllerian hormone serum (AMH) levels (P = .0005) than group 2. The IHC analysis demonstrated higher expression of AMH, FSH receptor, inhibin A, and inhibin B in growing follicles of group 3 versus group 2. Tracking studies demonstrated that human BMSCs evenly repopulated the growing follicles in treated ovaries. Importantly, breeding data showed significant increases in the pregnancies numbers, 2 pregnancies in group 1 and 12 in group 3 (P = .02). Conclusions: Intraovarian administered BMSCs are able to restore ovarian hormone production and reactivate folliculogenesis in chemotherapy-induced ovarian failure mouse model.