Abstract
Dioxins are ubiquitous and persistent environmental contaminants whose background levels are still reason for concern. There is mounting evidence from both epidemiological and experimental studies that paternal exposure to the most potent congener of dioxins, 2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD), can lower the male/female ratio of offspring. Moreover, in laboratory rodents and zebrafish, TCDD exposure of parent animals has been reported to result in reduced reproductive performance along with other adverse effects in subsequent generations, foremost through the paternal but also via the maternal germline. These impacts have been accompanied by epigenetic alterations in placenta and/or sperm cells, including changes in methylation patterns of imprinted genes. Here, we review recent key studies in this field with an attempt to provide an up-to-date picture of the present state of knowledge to the reader. These studies provide biological plausibility for the potential of dioxin exposure at a critical time-window to induce epigenetic alterations across multiple generations and the significance of aryl hydrocarbon receptor (AHR) in mediating these effects. Currently available data do not allow to accurately estimate the human health implications of these findings, although epidemiological evidence on lowered male/female ratio suggests that this effect may take place at realistic human exposure levels.
Highlights
It is a well-known fact that maternal lifestyle and exposure to environmental factors during pregnancy are important for the health of the offspring
Among the genes induced by TCDD are at least two whose products act as suppressors of aryl hydrocarbon receptor (AHR) activity, forming a feedback loop: AHR repressor (AHRR) and TCDD-inducible poly-ADPribose transferase (TiPARP) [46,47,48]
A great majority of the biological effects of TCDD and other dioxins scrutinized to date have proven to be mediated through the canonical signaling route, the AHR has other modes of action
Summary
It is a well-known fact that maternal lifestyle and exposure to environmental factors during pregnancy are important for the health of the offspring. As potent and persistent environmental dioxins are are stilldata raising concerns adverse effects on human health [6]. Dioxin-induced alterations have been shown be transferred to generations predominantly via male germline after exposures during susceptibility windows of epigenetic predominantly male germline duringworthwhile susceptibility windows of epigenetic reprogrammingvia of primordial germafter cells exposures [7]. Flaws [8] summarized themale transgenerational effects of a whole range of different types Brehm of endocrine disrupting chemicals on and female reproduction. Whole range of different types of endocrine disrupting chemicals on male and female reproduction The purpose of this mini review is to of focus on available data on paternally and maternally mediated multiand transgenerational effects dioxins.
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