Tropical Journal of Pharmaceutical Research

Original Research Article | OPEN ACCESS

Mitigation of premature ovarian failure by over-expression of lentivirus vector-mediated Wilms tumor-suppressor gene

Juan Wang, Le Bo, Wendan Xu, Xuekai Li, Bin Jiang, Caiping Mao

Reproductive Medicine Center, The First Affiliated Hospital of Soochow University, Suzhou, China;

For correspondence:- Caiping Mao Email: mp1161@163.com Tel:+8651267780720

Accepted: 27 August 2018 Published: 30 September 2018

Citation: Wang J, Bo L, Xu W, Li X, Jiang B, Mao C. Mitigation of premature ovarian failure by over-expression of lentivirus vector-mediated Wilms tumor-suppressor gene. Trop J Pharm Res 2018; 17(9):1745-1751 doi: 10.4314/tjpr.v17i9.9

© 2018 The authors.
This is an Open Access article that uses a funding model which does not charge readers or their institutions for access and distributed under the terms of the Creative Commons Attribution License (http://creativecommons.org/licenses/by/4.0) and the Budapest Open Access Initiative (http://www.budapestopenaccessinitiative.org/read), which permit unrestricted use, distribution, and reproduction in any medium, provided the original work is properly credited..

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)R09;GFP(green fluorescent protein)R09;WT1 group (POF mice given intra-ovarian microinjection of LVR09;GFPR09;WT1, a WT1R09;overexpressing 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). Radio-immunoassays 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