During gametogenesis, DNA undergoes demethylation and remethylation in order to erase previous imprints and reestablish sex-specific imprints. It was thought that this cycle would also remove epigenetic marks related to environmental exposures, disease state and others. Recent studies suggest that epigenetic marks can be inherited and serve as a kind of memory of environmental factors. For instance, male fetal rats exposed to agricultural pesticides showed reduced sperm production when adult. Although there was no change in DNA-sequence, the decreased sperm productivity could be observed in the three subsequent generations notwithstanding no longer pesticide exposure (Kaiser, 2005). Epigenetic modifications are inherited via mitosis but are, other than mutations, potentially reversible.

First evidence for epigenetic inheritance in human individuals originate from epidemiologic studies. In Sweden, scientists studied the correlation between excessive food uptake during the prepubertal growth phase and increased risk for the offspring to develop cardiovascular diseases or diabetes, respectively. Actually, mortality rate for diabetes was significantly increased in case of excessive feeding of parental grandfathers during their phase of slow growth, i.e. between the age between 8 and 12 (Kaati et al. 2002). Between 1947 and 1971 more than 1 million US-American women were treated with diethylstilbesterol (DES, oral oestrogen) to prevent abortion, which caused abnormalities of uterus, cervix, and vagina in their progeny. Furthermore, an increased risk to come down with rare cancers of cervix and vagina -like clear-cell carcinoma- was observed (Li et al., 2003). An explanation for this transgenerational effect of DES could be vertical inheritance of DNA-methylation patterns of genes involved in uterine carcinogenesis.

The observations that an environmental toxin (e.g. endocrine disruptor) can have an inheritable epigenetic effect on the germ-line significantly impacts our understanding of the potential hazards of these compounds to human health, as well as all other mammalian species. Elucidation of epigenetic mechanisms, their causations and elicitors will hopefully help us get insight into the interactions between environmental agents and the genome/epigenome. Aims are the estimation of complex influences of bio hazardous substances on human health and the design of preventive and therapeutic strategies. Since both, embryonic development and health and reproduction of adults are concerned population genetic studies appear necessary.

For further information
Inherited epigenetic variation - revisiting soft inheritance (by Richards)
Epigenetic transgenerational actions of endocrine disruptors (by Anway and Skinner)
Genomic Imprinting: Parental differentiation of the genome (by Keith Killian)
Mechanisms of hormonal carcinogenesis (by Hilakivi-Clarke)