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

Sara A. Mohamed, Shahinaz M. Shalaby, Mohamed Abdelaziz, Soumia Brakta, William D Hill, Nahed Ismail, Ayman Al-Hendy

Research output: Contribution to journalArticle

13 Citations (Scopus)

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.

Original languageEnglish (US)
Pages (from-to)51-63
Number of pages13
JournalReproductive Sciences
Volume25
Issue number1
DOIs
StatePublished - Jan 1 2018

Fingerprint

Mesenchymal Stromal Cells
Infertility
Drug Therapy
Bone Marrow
Hormones
Breeding
Ovary
Serum
Immunohistochemistry
FSH Receptors
Weights and Measures
Pregnancy
Vaginal Smears
Estrous Cycle
Follicle Stimulating Hormone
Hematoxylin
Eosine Yellowish-(YS)
Inbred C57BL Mouse
Uterus
Estrogens

Keywords

  • chemotherapy
  • infertility
  • ovarian failure
  • stem cells

ASJC Scopus subject areas

  • Obstetrics and Gynecology

Cite this

Human Mesenchymal Stem Cells Partially Reverse Infertility in Chemotherapy-Induced Ovarian Failure. / Mohamed, Sara A.; Shalaby, Shahinaz M.; Abdelaziz, Mohamed; Brakta, Soumia; Hill, William D; Ismail, Nahed; Al-Hendy, Ayman.

In: Reproductive Sciences, Vol. 25, No. 1, 01.01.2018, p. 51-63.

Research output: Contribution to journalArticle

Mohamed, Sara A. ; Shalaby, Shahinaz M. ; Abdelaziz, Mohamed ; Brakta, Soumia ; Hill, William D ; Ismail, Nahed ; Al-Hendy, Ayman. / Human Mesenchymal Stem Cells Partially Reverse Infertility in Chemotherapy-Induced Ovarian Failure. In: Reproductive Sciences. 2018 ; Vol. 25, No. 1. pp. 51-63.
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AU - Hill, William D

AU - Ismail, Nahed

AU - Al-Hendy, Ayman

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N2 - 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.

AB - 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.

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