Effects of psychological stress in histone acetylation (537.2)

Recently, epigenetic factors, including histone modifications, and environmental factors have shown to play an active role in endometriosis. We have recently shown that the levels of histone de‐acetylates (HDACs) are higher and that histone acetylation marks are decreased in endometriosis lesions. Also, stress contribute to the development of higher number of lesions and inflammatory parameters are exacerbated. Psychological stress has shown to cause changes in the epigenome. We sought to test the hypothesis that in endometriotic tissue from rats exposed to stress, histone acetylation is modulated, which would impact gene expression and lead to higher severity of symptoms. This randomized controlled study consists of two groups of rats, both with surgically induced endometriosis: the experimental group, which was exposed to a 10‐day swim stress protocol and a control group, which was not exposed to stress. On day 60, all rats were sacrificed and examined for the presence of endometriotic vesicles, which were processed for protein extraction and western blot analysis for HDACs, and for acetylated H3K9 and H4K8, as well as the housekeeping gene GAPDH. Densitometry and statistical analyses were performed to the bands. We have standardized the conditions for Western blot analysis of HDAC2 (57kD), H3K9ac and H3K8ac (~20Kd). Our preliminary results identified a specific HDAC2 band, which is expressed at the highest level by a rat exposed to stress, characterized by higher number of lesions and worse inflammatory parameters. Next, we will conduct Western Blot for HDACs and histone marks in both groups and will evaluate possible correlations between protein levels and inflammatory parameters in this rat model. These studies may produce evidence in support of a possible role of stress in modulation of epigenetic markers in endometriosis. Due to the fact that HDACs can be targeted using inhibitors, which can become potential new therapies, these results have a high translational potential. Grant Funding Source : Supported by: NIH Grant #R25GM096955 and (NCCAM) #3 NC1R15AT006373.