Endocrine Abstracts

Background: Follicles imaturation, as the hallmark of polycystic ovarian syndrome caused by prenatal androgen exposure, is suspected to be effected through expression changes of related genes. The aim of this study was to evaluate gene expression and promoter methylation of GATA6 and Follistatin (FST), two factors involved in follicle maturation, in adult female rats prenatally exposed to androgen excess by comparing them with non-treated rats.

Material and methods: Eight pregnant Wistar rats in the experimental group were treated by subcutaneous injection of 5 mg free testosterone on day 20 of pregnancy, while controls (n=8) received 500 ml of solvent. DNAs and RNAs were extracted from ovarian theca cells of adult female off-springs of PNA (n=24) and controls (n=24). Relative expression and promoter methylation levels were measured using Cyber-green Real-Time PCR and bisulfite sequence PCR (BSP) methods, respectively.

Results: Compared to the control group, the relative expression of GATA6 and FST genes in the treated group was 2.08 fold (95% CI: 1.62–2.55; P<0.0001) for GATA6 and 0.85 fold (95% CI: 0.73–0.97; P=0.058) for FST. Along with decrease in the methylation percentage of 11 CpG sites of GATA6 promoter in the PNA group in comparison with controls, the methylation of −480 position, was significantly decreased by 6.72±4.66 and 41.69±15.78 percent for PNA and the controls, respectively (P=0.03). No significant difference was seen in methylation of FST promoter although the percentage of 17 CpG sites increases slightly in PNAs.

Conclusions: These results reveal that manifestation of PCOS-like phenotype following prenatal exposure to excess androgen is associated with alteration in the expression and promoter methylation of the particular CpG sites of follicle maturation involved genes.

Keywords: GATA6, FST, Gene Expression, Promoter Methylation, Prenatal androgenisation