Abstract
EPIGENETIC TRANSGENERATIONAL ACTIONS OF ENDOCRINE DISRUPTORS ON REPRODUCTION AND DISEASE: THE GHOSTS IN YOUR GENES
Biology of reproduction, Vol.77(Suppl_1), pp.63-64
07/01/2007
Abstract
Transgenerational effects of environmental toxicants, such as endocrine disruptors, significantly amplify the impact and health hazards of these compounds. One of the most sensitive periods to endocrine disruptor exposure is during embryonic gonadal sex determination when the germ line is undergoing a remethylation process. The objective of the research was to investigate endocrine disruptor actions on testis development and male reproduction. The model endocrine disruptors tested were vinclozolin, which acts as an anti-androgenic compound, and methoxychlor, that has metabolites that are both weak estrogenic and anti-androgenic compounds. Previous studies have shown that methoxychlor and vinclozolin can effect embryonic testis development at the time of testis morphogenesis and that this causes an increase in germ cell apoptosis in the adult. Interestingly, observations demonstrate that this spermatogenic defect is transgenerational (F1, F2, F3 and F4 generations) and are hypothesized to be due to a permanent altered DNA methylation of the germ-line through an epigenetic action of the endocrine disruptor. Abnormal testis development and germ cell differentiation caused by endocrine disruptors was found to be in part due to inappropriate control of the testis transcriptome. The expression of over 200 genes were found to be altered in the embryonic testis and surprisingly this altered transcriptome was similar for all vinclozolin generation (F1–F3) males. In addition to detection of the male testis disorder, as the animals age transgenerational effects on numerous other disease states were observed including tumor development, prostate disease and kidney disease. Recent observations also suggest transgenerational effects on behaviors such as sexual selection are associated with evolutionary biology. Therefore, the transgenerational epigenetic mechanism appears to involve the actions of an environmental compound at the time of sex determination to alter the epigenetic (i.e DNA methylation) programming of the germ line that then alters the transcriptomes of developing organs to induce disease development transgenerationally in a heritable manner. The suggestion that environmental factors can reprogram the germ line to induce epigenetic transgenerational disease states is a new paradigm in disease etiology and evolution not previously considered.
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Details
- Title
- EPIGENETIC TRANSGENERATIONAL ACTIONS OF ENDOCRINE DISRUPTORS ON REPRODUCTION AND DISEASE: THE GHOSTS IN YOUR GENES
- Creators
- Michael Skinner - Washington State University
- Publication Details
- Biology of reproduction, Vol.77(Suppl_1), pp.63-64
- Academic Unit
- Biological Sciences, School of
- Identifiers
- 99901080823101842
- Language
- English
- Resource Type
- Abstract