Umbilical Cord Mesenchymal Stem Cell Transplantation Prevents Chemotherapy-Induced Ovarian Failure via the NGF/TrkA Pathway in Rats

• Published in: BioMed research international 2019-01, Vol.2019 (2019), p.1-9
• Main Authors: Chen, Haohao, Wang, Wenqian, Zou, Libo, Zhang, Ning, Jiang, Jinzhan, Fu, Xiaoyan, Zheng, Qun, Ding, Mingxing
• Format: Article
• Language: English
• Subjects: Animals; Anti-Mullerian Hormone - blood; Antineoplastic Agents - adverse effects; Apoptosis; Apoptosis - drug effects; Biomedical research; Bone marrow; Cancer; Caspase; Caspase 3 - blood; Caspase-3; Chemotherapy; Cyclophosphamide; Cyclophosphamide - adverse effects; Embryos; Endocrinology; Enzyme-linked immunosorbent assay; Estrogens; Estrogens - blood; Failure; Female; Fertility; Flow cytometry; Follicle Stimulating Hormone - blood; Follicle-stimulating hormone; Folliculogenesis; Gonadotropin-Releasing Hormone - blood; Gonadotropins; Granulosa cells; Growth factors; Hormones; Humans; Immunoglobulins; Injection; Mesenchymal Stem Cell Transplantation - methods; Mesenchymal Stem Cells; Mesenchyme; Nerve growth factor; Nerve Growth Factor - blood; Nerve Growth Factor - metabolism; Ovary - pathology; Pituitary (anterior); Pregnancy; Primary Ovarian Insufficiency - chemically induced; Primary Ovarian Insufficiency - therapy; Proteins; Rats; Rats, Sprague-Dawley; Receptors, FSH - blood; Reproductive status; Rodents; Scientific equipment and supplies industry; Secretion; Senescence; Signal transduction; Stem cell transplantation; Stem cells; Transplantation; TrkA protein; Umbilical cord; Umbilical Cord - transplantation; Western blotting
• ISSN: 2314-6133; 2314-6141
• DOI: 10.1155/2019/6539294

Chemotherapy leads to a loss of fertility and reproductive endocrine function, thereby increasing the risk of premature ovarian failure (POF). Studies have suggested that the transplantation of mesenchymal stem cells could inhibit apoptosis in ovarian granulosa cells and improve follicular development. In the present study, the effects of human umbilical cord mesenchymal stem cell (UCMSC) transplantation on ovarian function after ovarian damage caused by chemotherapy and the mechanism underlying these effects were investigated. POF model rats were obtained by the intraperitoneal injection of cyclophosphamide, and cultured UCMSCs were transplanted by tail vein injection. Serum estrogen, follicle-stimulating hormone, gonadotropin releasing hormone, and anti-Mullerian hormone levels were detected by ELISA. Folliculogenesis was evaluated by histopathological examination. The expression levels of nerve growth factor (NGF), high affinity nerve growth factor receptor (TrkA), follicle-stimulating hormone receptor (FSHR), and caspase-3 were evaluated by western blotting and RT-qPCR. The natural reproductive capacity was assessed by pregnant rate and numbers of embryos. The results indicated that UCMSC transplantation recovered disturbed hormone secretion and folliculogenesis in POF rats. NGF and TrkA levels increased, while FSHR and caspase-3 decreased. The pregnancy rate of POF rats was improved. Therefore, UCMSCs could reduce ovarian failure due to premature senescence caused by chemotherapy, and the NGF/TrkA signaling pathway was involved in the amelioration of POF.