Author:
Haddad Yasmin Hamdy,Said Riham S.,Kamel Rehab,Morsy Engy M. El,El-Demerdash Ebtehal
Abstract
AbstractRadiotherapy is a well-known cause of premature ovarian failure (POF). Therefore, we investigated the molecular influence of genistein (GEN) on the ovarian reserve of rats exposed to ϒ-radiation. Female Sprague Dawley rats were exposed to a 3.2 Gy γ-radiation to induce POF and/or treated with either GEN (5 mg/kg, i.p.) or Ethinyl estradiol (E2; 0.1 mg/kg, s.c.), once daily for 10 days. GEN was able to conserve primordial follicles stock and population of growing follicles accompanied with reduction in atretic follicles. GEN restored the circulating estradiol and anti-Müllerian hormone levels which were diminished after irradiation. GEN has potent antioxidant activity against radiation-mediated oxidative stress through upregulating endogenous glutathione levels and glutathione peroxidase activity. Mechanistically, GEN inhibited the intrinsic pathway of apoptosis by repressing Bax expression and augmenting Bcl-2 expression resulted in reduced Bax/Bcl-2 ratio with subsequent reduction in cytochrome c and caspase 3 expression. These promising effects of GEN are associated with improving granulosa cells proliferation. On the molecular basis, GEN reversed ovarian apoptosis through up-regulation of ER-β and FOXL-2 with downregulation of TGF-β expression, therefore inhibiting transition of primordial follicles to more growing follicles. GEN may constitute a novel therapeutic modality for safeguarding ovarian function of females’ cancer survivors.
Publisher
Springer Science and Business Media LLC
Reference78 articles.
1. Nair, C. K. K., Parida, D. K. & Nomura, T. Radioprotectors in radiotherapy. J. Radiat. Res.42, 21–37 (2001).
2. Nelson, L. M. Clinical practice. Primary ovarian insufficiency. N. Engl. J. Med.360, 606–614 (2009).
3. Alhumaidha, K. A., Saleh, D. O., El Fattah, M. A. A., El-Eraky, W. I. & Moawad, H. Cardiorenal protective effect of taurine against cyclophosphamide-induced toxicity in albino rats. Can. J. Physiol. Pharmacol.94, 131–139 (2016).
4. Kumar, M. et al. Chromosomal abnormalities and oxidative stress in women with premature ovarian failure (POF). Indian J. Med. Res.135, 92–97 (2012).
5. Fu, Z.-H. et al. Uncoupling protein 2 combats oxidative damage to human sperm. Zhonghua Nan Ke Xue16, 516–519 (2010).
Cited by
28 articles.
订阅此论文施引文献
订阅此论文施引文献,注册后可以免费订阅5篇论文的施引文献,订阅后可以查看论文全部施引文献