scholarly journals Insights into the Protective Mechanisms of Tamoxifen in Radiotherapy-Induced Ovarian Follicular Loss: Impact on Insulin-Like Growth Factor 1

Endocrinology ◽  
2013 ◽  
Vol 154 (10) ◽  
pp. 3888-3899 ◽  
Author(s):  
Yasmen F. Mahran ◽  
Ebtehal El-Demerdash ◽  
Ahmed S. Nada ◽  
Azza A. Ali ◽  
Ashraf B. Abdel-Naim
Keyword(s):  
Oxidative Stress ◽  
Proliferating Cell Nuclear Antigen ◽  
Follicular Development ◽  
Ovarian Failure ◽  
Radioprotective Effect ◽  
Whole Body ◽  
Nuclear Antigen ◽  
Γ Irradiation ◽  
Protective Mechanisms ◽  
Proliferating Cell

Radiotherapy is one of the most common and effective cancer treatments. However, it has a profound impact on ovarian function, leading to premature ovarian failure. With the hope of preserving fertility in cancer survivors, the need for an effective radioprotective therapy is evident. The present study investigated the mechanism of the potential radioprotective effect of tamoxifen (TAM) on γ-irradiation-induced ovarian failure on experimental rats and the impact of the IGF-1 in the underlying protective mechanisms. Female Sprague Dawley rats were either exposed to single whole-body irradiation (3.2 Gy; lethal dose [LD20]) and/or treated with TAM (1 mg/kg). γ-Irradiation caused an array of ovarian dysfunction that was evident by assessment of hormonal changes, follicular development, proliferation marker (proliferating cell nuclear antigen), and oxidative stress as well as apoptotic markers. In addition, IGF-1/IGF-1 receptor axis expression was assessed using real-time RT-PCR and immunolocalization techniques. Furthermore, fertility assessment was performed. TAM significantly enhanced follicular development and restored the anti-Mullerian hormone level. Moreover, it ameliorated the deleterious effects of irradiation on oxidative stress, proliferating cell nuclear antigen expression, and apoptosis. Interestingly, TAM was shown to enhance the ovarian IGF-1 but not IGF-1 receptor, a property that contributed significantly to its radioprotective mechanisms. Finally, TAM regained the fertility that was lost after irradiation. In conclusion, TAM showed a radioprotective effect and saved the ovarian reserve and fertility through increasing anti-Mullerian hormone and the local IGF-1 level and counteracting the oxidative stress-mediated apoptosis.

scholarly journals Carvacrol and Thymol Modulate the Cross-Talk between TNF-α and IGF-1 Signaling in Radiotherapy-Induced Ovarian Failure

2019 ◽  
Vol 2019 ◽  
pp. 1-10
Author(s):  
Yasmen F. Mahran ◽  
Amira M. Badr ◽  
Alhanouf Aldosari ◽  
Raghad Bin-Zaid ◽  
Hind N. Alotaibi
Keyword(s):  
Oxidative Stress ◽  
Cross Talk ◽  
Ovarian Failure ◽  
Radioprotective Effect ◽  
Whole Body ◽  
Nuclear Antigen ◽  
Hormonal Changes ◽  
Tnf Α ◽  
Ovarian Damage ◽  
The Cross

Premature ovarian failure (POF) is a common cause of infertility in premenopausal women who are unavoidably exposed to cytotoxic therapy. Radiotherapy is one of the most effective cytotoxic treatments. However, the radiosensitivity of ovarian tissues limits its therapeutic outcome and results in the depletion of the primordial follicle and loss of fertility. Therefore, the need for an effective radioprotective therapy is evident especially when none of the current clinically used modalities for radioprotection succeeds efficiently. The present study investigated the potential radioprotective effect of carvacrol (CAR) (80 mg) or thymol (80 mg) on gamma- (γ-) irradiation-induced ovarian damage as well as their role in the cross-talk between IGF-1 and TNF-α signaling and antioxidative activity. In immature female Wister rats, a single dose of whole-body irradiation (3.2 Gy, L D 20 ) produced considerable ovarian damage, which was evident by histopathological findings and hormonal changes. Interestingly, pretreatment with CAR or thymol significantly enhanced the follicular development and restored the anti-Mullerian hormone (AMH), E2, and FSH levels. Both essential oils improved the irradiation-mediated oxidative stress and reduction in proliferating cell nuclear antigen (PCNA) expression. Moreover, irradiated rats exhibited an inverse relationship between IGF-1 and TNF-α levels two days post irradiation, which was further inverted by the pretreatment with CAR and thymol and ought to contribute in their radioprotective mechanisms. In conclusion, CAR and thymol showed a radioprotective effect and rescued the ovarian reserve mainly through counteracting oxidative stress and the dysregulated cross-talk between IGF-1 and TNF-α.

scholarly journals 202.Estrogen actions on follicle formation and early follicle development

2004 ◽  
Vol 16 (9) ◽  
pp. 202
Author(s):  
K. L. Britt ◽  
P. K. Saunders ◽  
S. J. McPherson ◽  
M. L. Misso ◽  
E. R. Simpson ◽  
...  
Keyword(s):  
Mrna Expression ◽  
Proliferating Cell Nuclear Antigen ◽  
Leydig Cells ◽  
Follicular Development ◽  
Primordial Follicle ◽  
Nuclear Antigen ◽  
Proliferative Index ◽  
Mouse Ovary ◽  
Primordial Follicles ◽  
Proliferating Cell

Estradiol 17 beta (E2) effects late follicular development whilst primordial follicle formation and early activation are thought to be independent of E2. To test this hypothesis we compared numbers of primordial and primary follicles in wildtype and E2 deficient ArKO mice, and the immunohistochemical staining or mRNA expression of Mullerian inhibiting substance (MIS), Wilms tumour 1 (WT-1), and growth differentiation factor (GDF9), known to effect early follicular differentiation. Proliferating cell nuclear antigen (PCNA) staining was a marker of proliferative index. The effects of E2 replacement for 3 wk in 7 wk old ArKO and wildtype mice on these parameters were also tested. We used unbiased, assumption-free stereological methods for quantification of early follicular numbers in the mouse ovary (1). ArKO mice had reduced numbers of primordial and primary follicles compared to wildtype (63%, p<0.001 and 60%, p=0.062 of Wt respectively). This reduction was not corrected by E2 treatment, suggesting that E2 effects the initial formation or activation of primordial follicles. There was a significant increase in the diameters of the oocytes in primordial follicles of ArKO mice compared to wildtype. There were no differences in the immunostaining of MIS, WT-1 and PCNA in primordial and primary follicles between wildtype and ArKO mice. The only difference was as a consequence of Sertoli and Leydig cells in ovaries of ArKO mice. GDF9 mRNA expression was markedly increased in ArKO ovaries. E2 treatment restored the ovarian follicular morphology, and consequently the immunostaining patterns, but had no effect on early follicle numbers. In conclusion, E2 has a role in controlling the size of the oocyte and primordial follicle pools in mice. Supported by NH&MRC RegKey #241000 and 198705. (1) Britt and Myers (2004) Reproduction 127,:569–580.

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