Mitigation of premature ovarian failure by over-expression of lentivirus vector-mediated Wilms tumor-suppressor gene
Purpose: To investigate the effect of WT1(Wilms tumor-suppressor gene) overexpression on premature ovarian failure (POF)-mediated ovarian dysfunction.
Methods: Three mice groups were used: control group (untreated mice), POF group (mice sterilized by intravenous injection of cyclophosphamide and busulfan), and POF-LV(lentiviral vector)GFP(green fluorescent protein)WT1 group (POF mice given intra-ovarian microinjection of LVGFPWT1, a WT1overexpressing lentiviral vector, one week after sterilization). Real time-PCR was employed to analyze in vitro WT1 overexpression levels. Overall ovarian function was measured by hormonal assay, H & E staining, and immuno-histochemical techniques.
Results: Overexpression of WT1 in mice models of POF alleviated ovarian granulosa cell (GC) damage, increased ovary weight, and significantly increased follicular number (p < 0.05). Radioimmunoassays revealed reduction in plasma estradiol (E2) and follicle-stimulating hormone (FSH, p < 0.05). However, results from immune-histochemical assays showed reduced Bax expression levels, and increased expression of Bcl-2 in WTI-overexpression mice, relative to POF mice.
Conclusion: Overexpression of WT1 may stimulate repair of ovarian tissue while improving endocrine function by inhibiting ovarian cell apoptosis signaling pathway in POF mice.
Keywords: Premature ovarian failure, Wilms tumor suppressor gene, Chemotherapy, Apoptosis, Estradiol