Role of SDF-1/CXCR4 and cytokines in the development of ovary injury in chemotherapy drug induced premature ovarian failure mice.

Abstract

OBJECTIVE:

To explore the mechanism of chemotherapy drug induced ovarian injury in premature ovarian failure (POF) mice.

METHODS:

C57BL/6 mice were treated with Cyclophosphamide and Busulfan by intraperitoneal injection. One week after treatment, the estrous cycles, folliculogenesis, ovarian endocrine function and ovarian histopathological changes were evaluated the ovarian function. The serum levels of cytokines, follicle stimulating hormone (FSH) and estradiol (E2) were measured by enzyme-linked immunosorbent assay (ELISA). The protein levels of SDF-1/CXCR4 and FSHR in ovary were evaluated by immunohistochemistry and Western blot analysis. The ovarian cells apoptosis was measured by TUNEL Assay.

RESULTS:

The ovaries from POF mice show the evidence of reduced ovarian function such as irregular estrous cycles, stromal hyperplasia, decreased follicle numbers, atresia follicles and less granular cell layer as well as corpora luteum. The lower levels of E2 and higher levels of FSH in serum characterize the ovarian injury; a great number of granular apoptotic cells were observed in the POF mice; the serum concentrations of pro-inflammatory cytokines of IL-6, IL-8 and TNF-α level were increased but anti-inflammatory cytokine of IL-10 was decreased. SDF-1/CXCR4 and FSHR expressed in ovaries were detected in the cytoplasm of preantral and antral follicles; the expression of SDF-1/CXCR4 was increased and FSHR was decreased in POF mice.

CONCLUSION:

Our data suggest that the inflammatory regulation, SDF-1/CXCR4 and cellular apoptosis in ovarian tissues are involved in the development of ovarian injury of POF. These data provide useful information to develop new therapeutic approach to treat POF disorders in the future.

• Authors: Qianqian Luo, Na Yin, Lianshuang Zhang, Wendan Yuan, Wei Zhao, Xiying Luan, Hongqin Zhang
• Journal: Life sciences (Life Sci) Vol. 179 Pg. 103-109 (Jun 15 2017) ISSN: 1879-0631 [Electronic] Netherlands
• PMID: 28478265 (Publication Type: Journal Article)
• Copyright: Copyright © 2017 Elsevier Inc. All rights reserved.

Chemical References

• Antineoplastic Agents, Alkylating
• CXCR4 protein, mouse
• Chemokine CXCL12
• Cxcl12 protein, mouse
• Cytokines
• Receptors, CXCR4
• Estradiol
• Cyclophosphamide
• Follicle Stimulating Hormone
• Busulfan

Topics

• Animals
• Antineoplastic Agents, Alkylating (administration & dosage, toxicity)
• Apoptosis (drug effects)
• Blotting, Western
• Busulfan (administration & dosage, toxicity)
• Chemokine CXCL12 (metabolism)
• Cyclophosphamide (administration & dosage, toxicity)
• Cytokines (blood)
• Enzyme-Linked Immunosorbent Assay
• Estradiol (blood)
• Female
• Follicle Stimulating Hormone (blood)
• In Situ Nick-End Labeling
• Mice
• Mice, Inbred C57BL
• Ovarian Follicle (drug effects)
• Primary Ovarian Insufficiency (chemically induced, pathology)
• Receptors, CXCR4 (metabolism)