March 6, 2012

Epigenetic alterations by pollutants heritable across generations

We are just learning how epigenetic alterations do not just affect the individual but can be as inheritable as DNA, at least for some generations, blurring the distinctions between heredability and environment. A new study found that all tested chemical pollutants caused inheritable epigenetic alterations:


Abstract


Environmental factors during fetal development can induce a permanent epigenetic change in the germ line (sperm) that then transmits epigenetic transgenerational inheritance of adult-onset disease in the absence of any subsequent exposure. The epigenetic transgenerational actions of various environmental compounds and relevant mixtures were investigated with the use of a pesticide mixture (permethrin and insect repellant DEET), a plastic mixture (bisphenol A and phthalates), dioxin (TCDD) and a hydrocarbon mixture (jet fuel, JP8). After transient exposure of F0 gestating female rats during the period of embryonic gonadal sex determination, the subsequent F1–F3 generations were obtained in the absence of any environmental exposure. The effects on the F1, F2 and F3 generations pubertal onset and gonadal function were assessed. The plastics, dioxin and jet fuel were found to promote early-onset female puberty transgenerationally (F3 generation). Spermatogenic cell apoptosis was affected transgenerationally. Ovarian primordial follicle pool size was significantly decreased with all treatments transgenerationally. Differential DNA methylation of the F3 generation sperm promoter epigenome was examined. Differential DNA methylation regions (DMR) were identified in the sperm of all exposure lineage males and found to be consistent within a specific exposure lineage, but different between the exposures. Several genomic features of the DMR, such as low density CpG content, were identified. Exposure-specific epigenetic biomarkers were identified that may allow for the assessment of ancestral environmental exposures associated with adult onset disease.

The most strongly demonstrated transgenerational effect is the early onset of puberty in females. Oddly enough it seems caused by the father's sperm.

According to SD:
The field opens new ground in the study of how diseases develop. While toxicologists generally focus on animals exposed to a compound, Skinner's work further demonstrates that diseases can also stem from older, ancestral exposures that are then mediated through epigenetic changes in sperm.

See also: category 'Epigenetics' in this and my old blog

3 comments:

  1. "Environmental factors during fetal development can induce a permanent epigenetic change in the germ line (sperm)"

    That seems to be contradictory to the claims in the article.

    "The most strongly demonstrated transgenerational effect is the early onset of puberty in females. Oddly enough it seems caused by the father's sperm".

    On the contrary, in spite of the opening lines of the abstract, the original damage does not seem to be transmitted from affected males. It looks to be transmitted from the originally affected females. It is subsequent generations that suffer sperm problems, presumably passed on epigenetically from their mothers. Quote:

    "After transient exposure of F0 gestating female rats during the period of embryonic gonadal sex determination, the subsequent F1–F3 generations were obtained in the absence of any environmental exposure".

    So the original exposure was to the female line, not the male. And the effects in the following generations may also be transmitted through the female line rather than through the sperm.

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  2. I almost quoted this in the entry:

    "The mechanism involved in these transgenerational phenotypes is the reprogramming of the germ line (sperm) during male sex determination [1], [3]. This altered sperm epigenome appears to be permanently reprogrammed and escapes the DNA methylation programming at fertilization to allow transgenerational transmission of the altered sperm epigenome, that then promotes all tissues developed from that sperm to have altered cell and tissue transcriptomes that can promote transgenerational disease [1]".

    ReplyDelete
  3. Thanks for that clarification.

    ReplyDelete

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