DES establishes altered epigenetic marks capable of transgenerational inheritance
2011 Study Abstract
Exposures to endocrine disrupting chemicals such as the model toxicant diethylstilbestrol (DES) and the omnipresent bisphenol A (BPA) are of particular concern in the context of development.
In utero exposure of mice to DES has been shown to result in the hypermethylation of the developmentally critical (specifically to uterine organogenesis) Hoxa10 gene.
Although not a genotoxic agent, epidemiologic evidence from individuals exposed to DES during the first 3 months in utero indicates an increase in vaginal clear cell carcinoma incidence and reproductive disorders as adults.
In addition, grandchildren of DES exposed women reported higher incidences of rare reproductive disorders; whether this reflects detection bias or possibly implicates a role for epigenetic transgenerational inheritance remains to be clarified.
Ruden et al. drawing similarities between DES and Hsp90 has proposed a mechanism through which DES establishes altered epigenetic marks capable of transgenerational inheritance, wherein DES plays a role in modifying H3K4 methylation by increasing the activity of the H3K4 methyltransferase SMYD3, thereby altering epigenetic control of various genes.
- Full study (free access) : Epigenomics in Environmental Health, Journal of andrology, Frontiers in Genetics, NCBI PubMed PMC3268636, 2011.
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