Interactions between polymorphisms in the aryl hydrocarbon receptor signalling pathway and exposure to persistent organochlorine pollutants affect human semen quality

Brokken, Leon J. S.; Lundberg, Peter; Spanò, Marcello; Manicardi, Gian Carlo; Struciński, Paweł; Góralczyk, Katarzyna; Zviezdai, Valentyna; Jönsson, Bo; Bonde, JP; Toft, Gunnar; Giwercman, Yvonne Lundberg; Giwercman, Aleksander

doi:10.1016/j.reprotox.2014.07.073

Cited by 18 publications

(8 citation statements)

References 71 publications

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“…Another study found that both the CAG and the GGN repeat length polymorphisms in exon 1 of the AR gene modified the association between EDCs and the proportion of Y bearing sperm, and this association was more pronounced if the men also had a common SNP (rs2292596) in AHRR that made it less able to repress AHR [ 83 ]. Common variants that mediate the stability of the AHR gene and the repressing function of the AHRR gene also mediate the association between EDCs, including PCBs, and reproductive function [ 84 ]. Differences in genes related to steroid-hormone and xenobiotic pathways may explain why many health outcomes only associate with exposure to EDCs in some populations, and the difficulty that studies have in finding an association between the exposure dose and health outcomes [ 85 , 86 ].…”

Section: Genetics Of Pbb Exposurementioning

confidence: 99%

Intergenerational Effects of Endocrine-Disrupting Compounds: A Review of the Michigan Polybrominated Biphenyl Registry

et al. 2018

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Endocrine-disrupting compounds (EDCs) are a broad class of chemicals present in many residential products that can disrupt hormone signaling and cause health problems in humans. Multigenerational cohorts, like the Michigan polybrominated biphenyl registry, are ideal for studying the effects of intergenerational exposure. Registry participants report hormone-related health problems, particularly in those exposed before puberty or those in the second generation exposed through placental transfer or breastfeeding. However, more research is needed to determine how EDCs cause health problems and the mechanisms underlying intergenerational exposure. Utilizing existing data in this registry, along with genetic and epigenetic approaches, could provide insight to how EDCs cause human disease and help to determine the risk to exposed populations and future generations.

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Section: Genetics Of Pbb Exposurementioning

confidence: 99%

Intergenerational Effects of Endocrine-Disrupting Compounds: A Review of the Michigan Polybrominated Biphenyl Registry

et al. 2018

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“…Humans are more resistant to dioxins than many other animals, including laboratory rodents [24]. Traditionally, it is considered that the frequency of polymorphisms within AhR is low in humans resulting in small variations in susceptibility to DLCs across populations [24]; however, a recent study of a Greenland population reported that AhR variants significantly modify association between serum levels of DLCs and sperm characteristics, including chromatin integrity measured by TUNEL assay and concentration of zinc in seminal plasma [25]. …”

Section: Introductionmentioning

confidence: 99%

Spermatogenesis disruption by dioxins: Epigenetic reprograming and windows of susceptibility

Pilsner

Parker

Sergeyev

et al. 2017

Reproductive Toxicology

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Dioxins are a group of highly persistent chemicals that are generated as by-products of industrial and natural processes. Reduction in sperm counts is among the most sensitive endpoints of dioxin toxicity. The exact mechanism by which dioxins reduce sperm counts is not known. Recent data implicate the role of epididymal factors rather than disruption of spermatogenesis. Studies reviewed here demonstrate that dioxins induce the transfer of environmental conditions to the next generation via male germline following exposures during the window of epigenetic reprogramming of primordial germ cells. Increased incidence of birth defects in offspring of male veterans exposed to dioxin containing, Agent Orange, suggest that dioxins may induce epigenomic changes in male germ cells of adults during spermatogenesis. This is supported by recent animal data that show that environmental conditions can cause epigenetic dysregulation in sperm in the context of specific windows of epigenetic reprogramming during spermatogenesis.

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“…The effect of AhR signalling could be stimulatory or inhibitory, depending on other factors such as the level of dioxin exposure, the period of sensitivity and/or development of the target cells, and the actual level of key regulatory molecules, including the androgenoestrogen balance [46]. Moreover, polymorphisms in genes involved in AhR signalling have also been associated with impaired semen quality [55].…”

Section: Discussionmentioning

confidence: 99%

Relationship between serum dioxin-like polychlorinated biphenyls and post-testicular maturation in human sperm

Paul

Moltó

García

et al. 2017

Reproductive Toxicology

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The relationship between dioxin-like polychlorinated biphenyl (DL-PCB) levels in serum and semen parameters were investigated. Our case-control included two groups of patients. Total concentrations of PCBs were significantly higher in the low semen quality (n=24) than in the normal semen quality (n=26) group. A significant negative correlation was found between PCB 126 and viability in men with low semen quality, while PCBs 77 and 81 were positively correlated with morphology, and PCB 118, mono-ortho and total DL-PCBs were positively correlated with volume. In the normal semen quality group, PCB 189 and 118 were negatively correlated with sperm motility and volume, respectively. In addition, positive significant correlations were found between PCB 77, 23 and total non-ortho PCBs with regard to morphology. Our findings suggest that sperm motility, viability, volume and morphology are parameters sensitive to alteration by exposure to DL-PCBs, although PCB effects on spermatogenesis were not of clinical significance.

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Interactions between polymorphisms in the aryl hydrocarbon receptor signalling pathway and exposure to persistent organochlorine pollutants affect human semen quality

Cited by 18 publications

References 71 publications

Intergenerational Effects of Endocrine-Disrupting Compounds: A Review of the Michigan Polybrominated Biphenyl Registry

Intergenerational Effects of Endocrine-Disrupting Compounds: A Review of the Michigan Polybrominated Biphenyl Registry

Spermatogenesis disruption by dioxins: Epigenetic reprograming and windows of susceptibility

Relationship between serum dioxin-like polychlorinated biphenyls and post-testicular maturation in human sperm

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