Abstract
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
Highlights
Chemotherapy-induced premature ovarian failure (POF) and infertility are areas of immense interest to clinicians
Chemotherapy-induced POF and infertility are areas of immense interest to clinicians. This is due to rising incidence of malignant tumors and chemotherapy-induced POF, as well as increasing population of relatively young patients with malignant ovarian tumors [1,2]
A 90 % lentiviral infection efficiency was successfully effected in granulosa cell (GC) by LV-GFP-WT1 treatment, as confirmed by quantification of GFP expression 72 h after transfection (Figure 2 A)
Summary
Chemotherapy-induced POF and infertility are areas of immense interest to clinicians. This is due to rising incidence of malignant tumors and chemotherapy-induced POF, as well as increasing population of relatively young patients with malignant ovarian tumors [1,2]. Apart from POF and infertility, chemotherapy is accompanied by complications such as anorexia, amenorrhea, cardiovascular diseases and osteoporosis, all of which severely impact the life quality of young cancer survivors [3]. Fertilityenhancing treatments are available for POF patients. These include in vitro fertilization and hormonal therapy [4]. There are limited options for patients with chemotherapyinduced POF.
Sign-in/Register to view highlights & summary Talk to us
Join us for a 30 min session where you can share your feedback and ask us any queries you have
Schedule a callDisclaimer: All third-party content on this website/platform is and will remain the property of their respective owners and is provided on "as is" basis without any warranties, express or implied. Use of third-party content does not indicate any affiliation, sponsorship with or endorsement by them. Any references to third-party content is to identify the corresponding services and shall be considered fair use under The CopyrightLaw.
