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Lentivirus-Mediated bcl-2 Gene Therapy Improves Function and Structure of Chemotherapy-Damaged Ovaries in Wistar Rats

Authors


Correspondence

Yuanli He, Department of Obstetrics and Gynecology, Zhujiang Hospital, Southern Medical University, Guangzhou, Guangdong 510282, P. R. China.

E-mail: hyl@gdvnet.com

Abstract

Objective

This study aimed to explore the roles and mechanisms of lentivirus-mediated bcl-2 gene therapy in repairing the function and structure of chemotherapy-damaged ovaries in rats.

Method of Study

The lentivirus vector carrying the bcl-2 gene (pGC-FU -EGFP-bcl-2) was constructed and condensed at a high titer. Wistar rats were divided into seven groups based on the treatment they were given: no treatment [the normal control (NC) group]; intraperitoneal injection of cyclophosphamide (the CTX group); bilateral ovarian injection of pGC-FU-EGFP-bcl-2 (the bcl-2 group) or empty vector pGC-FU-EGFP (the enhanced green fluorescent protein (EGFP) group); bilateral ovarian injection of normal saline (the NS + CTX group), pGC-FU-EGFP (the EGFP + CTX group), or pGC-FU-EGFP-bcl-2 (the bcl-2 + CTX group) followed by intraperitoneal injection of CTX. At 15, 30, 45, and 60 days after injection, the rats were killed, serum levels of estradiol (E2) and follicle-stimulating hormone (FSH) were detected by radioimmunoassay; ovarian structure and follicles were observed under a microscope, the apoptosis of granulosa cells was detected by terminal deoxynucleotidyide transferase-mediated biotin–dUTP biotin nick-end labeling, and the expression of Bcl-2 in the ovaries was detected by Western blotting.

Results

After the injection of pGC-FU-EGFP-bcl-2, the serum level of E2 was elevated, whereas that of FSH was dropped, follicles were increased, the CTX-induced apoptosis of granulosa cells was inhibited, and the expression of Bcl-2 was up-regulated.

Conclusion

The lentivirus-mediated bcl-2 gene therapy can improve ovarian function and structure damaged by chemotherapy and, therefore, might be a potential method to treat CTX-induced pre-mature ovarian failure.

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