title: Lentivirus-mediated bcl-2 gene therapy improves function and structure of chemotherapy-damaged ovaries in wistar rats.
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.
  
  
  METHODS
  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.
  
  
  CONCLUSIONS
  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.
authors: Department of Obstetrics and Gynecology, Zhujiang Hospital, Southern Medical University, Guangzhou, Guangdong, P. R. China.
authors: Xuefeng
authors: X
authors: Wang
authors: Yuanli
authors: Y
authors: He
authors: Mubiao
authors: M
authors: Liu
authors: Xiafei
authors: X
authors: Fu
mesh_terms: D000818:Animals; D003001:Cloning, Molecular; D003520:Cyclophosphamide / Q000008:administration & dosage / Q000009:adverse effects; D064420:Drug-Related Side Effects and Adverse Reactions; D004958:Estradiol / Q000097:blood; D005260:Female; D005640:Follicle Stimulating Hormone / Q000097:blood; D015316:Genetic Therapy / Q000379:methods*; D005822:Genetic Vectors / Q000235:genetics; D016086:Lentivirus; D010049:Ovarian Diseases / Q000139:chemically induced / Q000235:genetics / Q000473:pathology / Q000628:therapy*; D010053:Ovary / Q000187:drug effects / Q000473:pathology*; D019253:Proto-Oncogene Proteins c-bcl-2 / Q000008:administration & dosage* / Q000235:genetics / Q000378:metabolism; D051381:Rats; D017208:Rats, Wistar
chemical_list: D019253:Proto-Oncogene Proteins c-bcl-2; D004958:Estradiol; D003520:Cyclophosphamide; D005640:Follicle Stimulating Hormone