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Reprod Sci. 2018 Jan;25(1):51-63. doi: 10.1177/1933719117699705. Epub 2017 May 1.

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

Author information

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.

KEYWORDS:

chemotherapy; infertility; ovarian failure; stem cells

Comment in

PMID:
28460567
PMCID:
PMC6344979
DOI:
10.1177/1933719117699705
[Indexed for MEDLINE]
Free PMC Article

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