title: Gene-environment interactions in male reproductive health: special reference to the aryl hydrocarbon receptor signaling pathway.
abstract: Over the last few decades, there have been numerous reports of adverse effects on the reproductive health of wildlife and laboratory animals caused by exposure to endocrine disrupting chemicals (EDCs). The increasing trends in human male reproductive disorders and the mounting evidence for causative environmental factors have therefore sparked growing interest in the health threat posed to humans by EDCs, which are substances in our food, environment and consumer items that interfere with hormone action, biosynthesis or metabolism, resulting in disrupted tissue homeostasis or reproductive function. The mechanisms of EDCs involve a wide array of actions and pathways. Examples include the estrogenic, androgenic, thyroid and retinoid pathways, in which the EDCs may act directly as agonists or antagonists, or indirectly via other nuclear receptors. Dioxins and dioxin-like EDCs exert their biological and toxicological actions through activation of the aryl hydrocarbon-receptor, which besides inducing transcription of detoxifying enzymes also regulates transcriptional activity of other nuclear receptors. There is increasing evidence that genetic predispositions may modify the susceptibility to adverse effects of toxic chemicals. In this review, potential consequences of hereditary predisposition and EDCs are discussed, with a special focus on the currently available publications on interactions between dioxin and androgen signaling.
authors.affiliation: Department of Clinical Sciences, Molecular Genetic Reproductive Medicine, Lund University, Malmö, Sweden.
authors.forename: Leon J S
authors.initials: LJ
authors.lastname: Brokken
authors.forename: Yvonne Lundberg
authors.initials: YL
authors.lastname: Giwercman
mesh_terms: D000818:Animals; D004147:Dioxins / Q000633:toxicity; D052244:Endocrine Disruptors / Q000633:toxicity*; D004785:Environmental Pollutants / Q000633:toxicity; D059647:Gene-Environment Interaction; D020022:Genetic Predisposition to Disease; D006801:Humans; D008297:Male; D011944:Receptors, Androgen / Q000187:drug effects / Q000235:genetics; D018336:Receptors, Aryl Hydrocarbon / Q000187:drug effects* / Q000235:genetics; D060728:Reproductive Health; D015398:Signal Transduction / Q000187:drug effects; D012907:Smoking / Q000009:adverse effects / Q000235:genetics
chemical_list: D004147:Dioxins; D052244:Endocrine Disruptors; D004785:Environmental Pollutants; D011944:Receptors, Androgen; D018336:Receptors, Aryl Hydrocarbon