ESPE Abstracts (2015) 84 P-1-136

Turner & Puberty

The Eap1 Promoter is Differentially Methylated at the Onset of Puberty in Normal Weight and Obese Female Rats

Hanna Moellerb & Sabine Hegera,b


aChildren’s Hospital Bult, Hannover, Germany; bInstitute of Clinical Biochemistry, Hannover Medical School, Hannover, Germany

Background: Mammalian puberty is initiated by the pulsatile release of gonadotropin-releasing hormone (GnRH) from hypothalamic neurons. Enhanced at puberty (Eap) 1 is a transcription factor within this regulatory network integrating exogenous and endogenous informations, e.g. weight. Recent studies indicate an epigenetic regulation of the pubertal process.

Objective and hypotheses: This study investigates if overweight modifies epigenetic marks in the Eap1 promoter resulting in an altered function.

Method: Female rats were raised in small (n=3) and normal litters (n=12). Weight, vaginal opening (VO) and estrous cycle were recorded. At different developmental time points methylation and expression profiles were analysed.

Results: Rats growing up in small litters are significantly heavier than control rats. Furthermore obese rats show an earlier VO by one day and are significantly heavier at VO (151g±2.3 vs 131g±1.8, P<0.001). Within the first CpG island of the Eap1 promoter region (−4028bp to −3703bp upstream TSS) the methylation level differs significantly between prepubertal and pubertal phases (11%±0.6 vs 26%±1.0, P<0.001, n=6). In obese rats the methylation level at the beginning of puberty is significantly blunted compared to normal weight rats (16%±1.5 vs 26%±1.0, P<0.001). The expression level of Eap1 increases at PND 30 in normal weight and obese rats.

Conclusion: These results show differences in the methylation level between pre- and pubertal phases influenced by endogenous factors, like weight. This might explain why moderate obesity advances pubertal onset. Further studies utilising luciferase promoter assays in CpG free vectors will proof the functional relevance.

Funding information: This work was supported by the German Research Council (HE3151/4-2).

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