Abstract

Premature ovarian failure (POF) is one of the most common causes of infertility in women. In our present study, we established cyclophosphamide- (CTX-) induced POF rat model and elucidated its effect on ovarian function. We detected the serum estrogen, follicle stimulating hormone, and anti-Müllerian hormone of mice models by ELISA and evaluated their folliculogenesis by histopathology examination. Our study revealed that CTX administration could severely disturb hormone secretion and influence folliculogenesis in rat. This study also detected ovarian cells apoptosis by deoxy-UTP-digoxigenin nick end labeling (TUNEL) and demonstrated marked ovarian cells apoptosis in rat models following CTX administration. In order to explore the potential of human umbilical cord mesenchymal stem cells (UCMSCs) in POF treatment, the above indexes were used to evaluate ovarian function. We found that human UCMSCs transplantation recovered disturbed hormone secretion and folliculogenesis in POF rat, in addition to reduced ovarian cell apoptosis. We also tracked transplanted UCMSCs in ovaries by fluorescence in situ hybridization (FISH). The results manifested that the transplanted human UCMSCs could reside in ovarian tissues and could survive for a comparatively long time without obvious proliferation. Our present study provides new insights into the great clinical potential of human UCMSCs in POF treatment.

Highlights

  • Premature ovarian failure (POF) is a heterogeneous disorder, which is defined as the cessation of ovarian function, along with elevated follicle stimulating hormone (FSH) and decreased estrogen (E2) levels in women below 40 years [1]

  • The results indicated a high expression of CD90/CD29/CD73/CD105 (>95%) for the isolated human umbilical cord mesenchymal stem cells (UCMSCs) (Figures 1(a), 1(b), 1(c), and 1(e))

  • Our results indicated a significant increase in secondary follicles in UCMSCs trans

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Summary

Introduction

Premature ovarian failure (POF) is a heterogeneous disorder, which is defined as the cessation of ovarian function, along with elevated follicle stimulating hormone (FSH) and decreased estrogen (E2) levels in women below 40 years [1]. Ovarian atrophy, reduced follicle stores, menstrual irregularities, and ovarian dysfunction are the most important characteristics of POF. It has become an important cause of infertility. Stem cell transplantation has become a promising tool in rescuing damaged ovarian function. We established chemotherapy induced POF rat models, which represent a reliable and physiological model for studying the role of CTX in murine ovarian function. The cells were resuspended in 0.5 mL PBS to obtain a final concentration of 2 × 105 cells and were analyzed by FACSCalibur Flow Cytometer (BD FACSCalibur)

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