ABSTRACT
Lipophilic persistent organic pollutants (POPs) are ubiquitous in the environment and suspected to interfere with hormone activities and reproduction. In previous studies we demonstrated that POP exposure can affect sperm DNA integrity and differences between Inuits and Europeans in sperm DNA integrity and xenobiotic activity were observed. The aim of this study was to investigate possible relations between human sperm chromatin integrity and the xenobiotic serum activity of lipophilic POPs assessed as effects on the estrogen (ER), androgen (AR), and/or aryl hydrocarbon (AhR) receptors. Human sperm chromatin integrity was assessed as DNA fragmentation index (%DFI) and high DNA stainability (%HDS) using the flow cytometric sperm chromatin structure assay (SCSA). Xenobiotic receptor activities were determined using chemically activated luciferase gene expression (CALUX) assay. The study included 53 Greenlandic Inuits and 247 Europeans (Sweden, Warsaw (Poland) and Kharkiv (Ukraine)). A heterogeneous pattern of correlations was found. For Inuits, ER and AhR activities and %DFI were inversely correlated, whereas a positive correlation between AR activity and %DFI was found for Europeans. In contrast, no correlation between receptor activities and %HDS was observed for Inuits but for Europeans positive and negative correlations were observed between ER and AR activities and %HDS, respectively. We suggest that the different patterns of xenobiotic serum activities, in combination with diet associated factors and/or genetics, might be connected to the observed differences in sperm chromatin integrity between the Inuits and Europeans.
Subject(s)
Chromatin/metabolism , Environmental Pollutants/blood , Inuit , Spermatozoa/metabolism , White People , Xenobiotics/blood , Chromatin/chemistry , Chromatin/drug effects , Cohort Studies , DNA Fragmentation/drug effects , Environmental Exposure , Environmental Pollutants/toxicity , Humans , Inuit/genetics , Male , Receptors, Androgen/genetics , Receptors, Androgen/metabolism , Receptors, Aryl Hydrocarbon/genetics , Receptors, Aryl Hydrocarbon/metabolism , Receptors, Estrogen/genetics , Receptors, Estrogen/metabolism , Reproducibility of Results , Spermatozoa/chemistry , Spermatozoa/drug effects , White People/genetics , Xenobiotics/toxicityABSTRACT
Persistent organic pollutants (POPs) can interfere with hormone activities and are suspected as endocrine disrupters involved in disorders, e.g. reproductive disorders. We investigated the possible relation between the actual integrated serum xenoestrogenic, xenoandrogenic and aryl hydrocarbon receptor (AhR) activities, and the sperm DNA damage and sperm apoptotic markers of 262 adult males (54 Inuits from Greenland, 69 from Warsaw (Poland), 81 from Sweden, and 58 from Kharkiv (Ukraine)) exposed to different levels of POPs. Xenobiotic-induced receptor activities were determined by receptor-mediated luciferase reporter gene expression. Sperm DNA damage was measured using terminal deoxynucleotidyl transferase-driven dUTP nick labeling assay (TUNEL) and pro- (Fas) and anti-apoptotic (Bcl-xL) markers were determined by immune methods. Different features of xenobiotic-induced receptor activity in serum and sperm DNA fragmentation and apoptotic markers existed between the Inuits and the European Caucasians. Negative correlations between xenobiotic-induced receptor activities and DNA damage were found for Inuits having relatively lower xenoestrogenic, lower dioxin-like activity, and lower sperm DNA damage, but higher xenoandrogenic activity. In contrast, in the European groups, xenobiotic-induced receptor activities were found to be positively correlated with the DNA damage. Further research must elucidate whether altered receptor activities in concerted action with genetic and/or nutrient factors may have protecting effect on sperm DNA damage of the Inuit population.
Subject(s)
Endocrine Disruptors/toxicity , Environmental Pollutants/toxicity , Inuit , Spermatozoa/drug effects , White People , Adult , Apoptosis , Cells, Cultured , Comet Assay , DNA Damage , Dioxins/toxicity , Dose-Response Relationship, Drug , Environmental Exposure , Gene Expression , Greenland , Humans , In Situ Nick-End Labeling , Luciferases/genetics , Male , Poland , Receptors, Androgen/blood , Receptors, Aryl Hydrocarbon/blood , Receptors, Estrogen/blood , Spermatozoa/metabolism , Spermatozoa/pathology , Sweden , Ukraine , XenobioticsABSTRACT
Organochlorines are widespread pollutants in humans. Concern about adverse reproductive effects of these compounds arises from accidental exposure of humans and experimental studies. Recently, this issue has been addressed by a number of studies of exposed populations and hospital-based case-referent studies. These studies indicate that high concentrations of persistent organochlorines may adversely affect semen quality and cause testicular cancer in males, induce menstrual cycle abnormalities and spontaneous abortions in females, and cause prolonged waiting time pregnancy, reduced birth weight, skewed sex ratio, and altered age of sexual development. However, most effects have been demonstrated at exposure levels above the present day exposure level in European and North American populations. Due to inherent methodological problems in several of the available studies, additional research is needed to fully elucidate the possible adverse effects of organochlorines on human reproductive health.
