The MODULATION OF GENES AND PROTEIN LOCALIZATION FOR ESTROGEN AND PROGESTERONE RECEPTORS IN CYCLOPHOSPHAMIDE-EFFECTED OVARY BY TOCOTRIENOLS SUPPLEMENTATION
Modulation of Genes and Protein Localization for Estrogen and Progesterone Receptors in Cyclophosphamide-effected Ovary by Tocotrienols Supplementation
Objective: The objective of the study was to investigate the role of tocotrienols (T3) in alteration and regulation of estrogen receptor (ER) and progesterone receptor (PR) genes and proteins expression that was hoped to explain the involvement of ER and PR signaling pathway as biomarker in maintaining fertility during chemotherapy treatment.
Methods: Fifty female ICR mice (10–12) weeks were equally divided into five groups: CPA, CPA and T3, normal saline, T3 only, and corn oil only. The treatment was given for 4 weeks and followed by super ovulation protocol application. Both ovaries were removed, RNA extraction and real-time quantitative polymerase chain reaction (PCR) were performed using the super green probe real-time PCR. Concentration of the forward, reverse primers involvement ER, PR, glyceraldehyde-ᴣ-phosphate dehydrogenase and α-actin genes. Histological processing was performed to apply IHC reactions using peroxidase for mouse biotinylated primary antibody.
Result: It was founded that significant downregulation of ERα gene was evident in the coadministration of CPA with T3 compared to CPA group (p<0.01). Meanwhile, highly significant expression of ERα gene in CPA-exposed ovary compared to the control group, which was by 5.9-fold (p<0.01). Moreover, the study revealed that CPA+ T3 is significantly reduced the protein localization of ER, PR in the ovary of CPA−exposed mice (p<0.05).
Conclusion: The results indicated that coadministration of T3 with CPA confers protection against altered genes and protein expression in ovaries. T3 may consider as a promising candidate for ovarian preservation due to chemotherapy-associated ER, PR genes, and protein overexpression.
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