Poster Presentation ESA-SRB 2023 in conjunction with ENSA

Exposure to diethylstilbestrol causes transgenerational effects on female fertility and reproductive development through altering DNA methylation (#367)

Rachael Rogers 1 , Deidre M Mattiske 1 , Andrew J Pask 1
  1. The University of Melbourne, Melbourne, Victoria, Australia

Endocrine disrupting chemicals (EDCs) are pervasive toxins in our environment that can block and/or interfere with normal hormonal signalling and action within the body. We are continuously exposed to EDCs in our everyday lives as they are present in plastics, pharmaceuticals, herbicides, and pesticides. Numerous studies have demonstrated the detrimental effects of EDCs on fertility and reproductive development. However, the most alarming impact of EDCs is their ability to cause effects that persist for multiple generations. Previously, we showed that prenatal exposure to the potent estrogenic EDC, diethylstilbestrol (DES), causes transgenerational reproductive effects in mice. Specifically, we observed that female descendants went through puberty significantly earlier, had a significantly smaller anogenital distance and experienced reduced fertility up until the third, unexposed generation. To determine the mechanisms by which DES is able to cause these transgenerational effects, we conducted whole genome methylation analysis on oocytes collected from control and F1 – F3 DES exposed mice. The methylation percentage was compared between these groups, and we found that global methylation was significantly higher in DES F2 and F3 generations compared the F1 generation. This indicates that DES is able to alter the epigenome by disrupting normal DNA methylation, which may then result in the observed transgenerational phenotype. These data provide insights into the mechanisms through which EDCs are able to elicit their long-lasting, transgenerational effects.