Sara A Mohamed1,2, Shahinaz M Shalaby1,3, Mohamed Abdelaziz1,2, Soumia Brakta1, William D Hill4, Nahed Ismail5, Ayman Al-Hendy1. 1. 1 Division of Translation Research, Department of Obstetrics and Gynecology, Medical College of Georgia Augusta University, Augusta, GA, USA. 2. 2 Department of Obstetrics and Gynecology, Mansoura Faculty of Medicine, Mansoura University Hospital, Mansoura, Egypt. 3. 3 Department of Pharmacology, Tanta Faculty of Medicine, Tanta, Egypt. 4. 4 Department of Cellular Biology and Anatomy, Medical College of Georgia, Augusta University, Augusta, GA, USA. 5. 5 Division of Clinical Microbiology, Department of Pathology, University of Pittsburgh Medical Center, Pittsburgh, PA, USA.
Abstract
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.
INTRODUCTION: Chemotherapy is the most commonly used modality to treat humancancers; 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 failuremouse 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 failuremouse model.
Authors: Alexander Rühle; Ramon Lopez Perez; Bingwen Zou; Anca-Ligia Grosu; Peter E Huber; Nils H Nicolay Journal: Stem Cell Rev Rep Date: 2019-06 Impact factor: 5.739