Differences in serum levels of CB-153 and p,p'-DDE, and reproductive parameters between men living south and north in Norway.

Arctic is contaminated with persistent organochlorine pollutants (POPs), and exposure to these compounds may differ between south and north in Norway. POPs may have negative impact on male reproductive characteristics. We compared serum levels of the CB-153 and p,p'-DDE in men who were born and had lived most of their lifetime south and north (close to or above the Arctic Circle) in Norway. We found no geographical differences in levels of CB-153 (south: 50 ng/g lipid (mean), north: 59 ng/g lipid; p=0.27) or sperm parameters. However, the levels of p,p'-DDE were higher in south than in north (81 ng/g lipid (mean) vs. 66 ng/g lipid; p=0.02), as were the levels of total and free testosterone. The FSH levels were lowest in south. A strong relationship between the CB-153 and the SHBG levels was observed. The regional differences observed for p,p'-DDE, testosterone and FSH were not reflected in the semen quality.

Association of maternal serum concentrations of 2,2', 4,4'5,5'-hexachlorobiphenyl (CB-153) and 1,1-dichloro-2,2-bis (p-chlorophenyl)-ethylene (p,p'-DDE) levels with birth weight, gestational age and preterm births in Inuit and European populations.

BACKGROUND: Epidemiological studies on the association between maternal exposure to persistent organic pollutants (POPs) and fetal growth alteration report inconsistent findings which weights in favor of additional studies. METHODS: Blood samples were collected from interviewed pregnant women in Greenland (572), Kharkiv (611) and Warsaw (258) and were analyzed for CB-153 and p,p'-DDE by gas chromatography-mass spectrometry. Data on birth weight, gestational age and preterm birth were obtained for 1322 singleton live births. We examined the association between natural log-transformed serum POPs concentration and birth weight and gestational age using multiple linear regression and the association with prematurity using logistic regression controlling for potential confounding factors. RESULTS: The median serum concentrations of CB-153 and p,p'-DDE were for Inuit mothers 105.6 and 298.9, for Kharkiv mothers 27.0 and 645.4 and for Warsaw mothers 10.7 and 365.2 ng/g lipids, respectively. Increase in CB-153 concentration by one unit on the log scale in Inuit mothers serum was associated with significant decrease in infant birth weight of -59 g and gestational age by -0.2 week. Decreases observed in the cohorts in Kharkiv (-10 g and -0.1 week) and in Warsaw (-49 g and -0.2 week) were not statistically significant. Increase in p,p'-DDE concentration by one unit on the log scale was associated with a statistically significant decrease in infant birth weight of -39.4 g and -104.3 g and shortening of gestational age of -0.2 week and -0.6 week in the Inuit and Warsaw cohorts, respectively. In the Kharkiv cohort decrease in birth weight (-30.5 g) was not significant, however a shortening of gestational age of -0.2 week per increase in p,p'-DDE concentration by one unit on the log scale was of the borderline significance. There was no significant association between CB-153 and p,p'-DDE concentrations and risk of preterm birth however, in all cohorts the odds ratio was above 1. CONCLUSIONS: In utero exposure to POPs may reduce birth weight and gestational age of newborns however, new insights as to why results vary across studies were not apparent.

Intra-individual variations and temporal trends in dioxin levels in human blood 1987-2002.

OBJECTIVES: In Sweden, an important source for exposure to persistent organochlorine pollutants, such as PCDD and PCDF, is through intake of fatty fish from the Baltic Sea off the Eastern coast of Sweden. The present study assesses temporal trends for human levels of PCDD/F between 1987 and 2002 among 26 men from Sweden. In addition, we investigate the impact of potential determinants (age, relative change in BMI and fish consumption) on the relatively change in individual PCDD/F congener levels between 1987 and 2002. METHODS: In 1987, nine of the men did not eat fatty fish from the Baltic Sea, eight had a moderate intake, and nine were high consumers. For the same individuals, blood samples were collected in 1987 as well as in 2002, and the concentrations of seven PCDD and 10 PCDF congeners were analyzed at the same laboratory. RESULTS: The WHO-TEQ levels for PCDD/F did not significantly change over the 15-year period. There were, however, some specific congeners that significantly had changed over time. None of the investigated determinants were associated with the change over time for the specific PCDD/F congeners. CONCLUSION: The present study may be of importance for risk assessment and setting standards for food contamination with PCDD/F, especially regarding intake of fatty fish from the Baltic Sea.

Rapid decline of persistent organochlorine pollutants in serum among young Swedish males.

To investigate a possible time trend in serum concentrations of persistent organochlorine pollutants (POPs), representative samples of the young (median age 18 years) Swedish male population were investigated in the years 2000 and 2004. Due to their low age, these men were assumed not to have reached steady state of body burdens of POPs, why their serum concentrations were considered to represent ongoing dietary exposure. Serum concentrations of 2,2',4,4',5,5'-hexachlorobiphenyl (CB-153) and 1,1-dichloro-2,2-bis(4-chlorophenyl)-ethylene (p,p'-DDE), two biomarkers of exposure to POPs, were available for 274 and 223 men, respectively, in 2000 and for 200 men in 2004. The percentage of men with CB-153 or p,p'-DDE below the limit of detection (LOD) was significantly higher in 2004 than in 2000 (30% vs. none, p < 0.001 for CB-153 and 65% vs. 6%, p < 0.001 for p,p'-DDE). Moreover, the median serum concentration of CB-153 decreased from 66 ng g(-1) lipid to 19 ng g(-1), corresponding to a yearly decrease of about 26%. The analogous analysis was not done for p,p'-DDE since the median serum concentration in 2004 was below the LOD.

Association between tobacco exposure and reproductive parameters in adolescent males.

Cigarette smoking is quite prevalent in the general population but our knowledge of its effect on male reproductive function is still very limited. Therefore, we investigated the impact of tobacco exposure on reproductive characteristics in young males. Military conscripts, 217 non-smokers and 85 smokers, with a median age of 18 years were enrolled. Physical examination and semen analysis, including measurement of accessory sex gland markers and reproductive hormone levels, were performed. Lifestyle-associated factors, including maternal smoking during pregnancy and snuffing, were recorded. Non-smokers had 49% higher total sperm number than smokers (95% CI 4.5-112%, p = 0.01). In addition, sperm concentration was 37% higher among non-smokers (95% CI -4% to 95%, p = 0.08). Serum levels of follicle-stimulating hormone (FSH) were 17% higher among non-smokers (95% CI 3-33%, p = 0.02), whereas no significant differences between smokers and non-smokers were found for inhibin B, testosterone, sex hormone binding globulin, luteinizing hormone and oestradiol. Those who smoked >10 cigarettes per day exhibited 37% lower (95% CI 10-69%, p = 0.005) FSH levels than those who smoked less. Maternal smoking during pregnancy had a negative impact on epididymal and seminal vesicle marker secretion. Smoking seems to impair sperm production and epididymal as well as accessory sex gland function and could be one of the factors contributing to regional differences in sperm parameters.

Fracture incidence in GH-deficient patients on complete hormone replacement including GH.

UNLABELLED: Fracture risk in GHD patients is not definitely established. Studying fracture incidence in 832 patients on GH therapy and 2581 matched population controls, we recorded a doubled fracture risk in CO GHD women, but a significantly lower fracture risk in AO GHD men. INTRODUCTION: The objective of this study was to evaluate fracture incidence in patients with confirmed growth hormone deficiency (GHD) on replacement therapy (including growth hormone [GH]) compared with population controls, while also taking potential confounders and effect modifiers into account. MATERIALS AND METHODS: Eight hundred thirty-two patients with GHD and 2581 matched population controls answered a questionnaire about fractures and other background information. Incidence rate ratio (IRR) and 95% CI for first fracture were estimated. The median time on GH therapy for childhood onset (CO) GHD men and women was 15 and 12 yr, respectively, and 6 and 5 yr for adult onset (AO) GHD men and women, respectively. RESULTS: A more than doubled risk (IRR, 2.29; 95% CI, 1.23-4.28) for nonosteoporotic fractures was recorded in women with CO GHD, whereas no risk increase was observed among CO GHD men (IRR, 0.61) and AO GHD women (IRR, 1.08). A significantly decreased incidence of fractures (IRR, 0.54; 95% CI, 0.34-0.86) was recorded in AO GHD men. CONCLUSIONS: Increased fracture risk in CO GHD women can most likely be explained by interaction between oral estrogen and the GH-IGF-I axis. The adequate substitution rate of testosterone (90%) and GH (94%) may have resulted in significantly lower fracture risk in AO GHD men.

Nonfatal stroke, cardiac disease, and diabetes mellitus in hypopituitary patients on hormone replacement including growth hormone.

CONTEXT: The impact of long-term GH replacement on cerebrovascular and cardiovascular diseases and diabetes mellitus in hypopituitary patients is unknown. OBJECTIVE: The incidence of nonfatal stroke and cardiac events, and prevalence of type 2 diabetes mellitus (T2D) and cardioprotective medication were compared between cohorts of GH-deficient (GHD) patients and population controls. DESIGN AND PARTICIPANTS: The incidence of nonfatal stroke and cardiac events was estimated retrospectively from questionnaires in 750 GHD patients and 2314 matched population controls. A prevalence of T2D and cardioprotective medication was recorded at the distribution of questionnaires. Time since first pituitary deficiency to start of GH therapy was 4 and 2 yr, and time on GH therapy was 6 yr for GHD women and men, respectively. RESULTS: Lifelong incidence of nonfatal stroke was tripled in GHD women and doubled in GHD men, but a decline was seen in both genders during periods after first pituitary hormone deficiency and GHD, during which most patients had GH therapy. The lifelong incidence of nonfatal cardiac events declined in GHD men during first pituitary hormone deficiency and GHD periods. GHD women had a higher prevalence of T2D and lipid-lowering medication, whereas GHD men had a higher prevalence of antihypertensive medication. CONCLUSIONS: The declined risks of nonfatal stroke in both genders and of nonfatal cardiac events in GHD men during periods on GH replacement may be caused by prescription of cardioprotective drugs and 6-yr GH replacement. GHD women had an increased prevalence of T2D, partly attributed to higher body mass index and lower physical activity.

Exposure to persistent organochlorine pollutants and type 2 diabetes mellitus.

Persistent organochlorine pollutants (POPs), such as polychlorinated biphenyls (PCBs), polychlorinated dibenzo-p-dioxins (PCDDs), dichloro diphenyl trichloroethane (DDT) and its major metabolite 1,1-dichloro-2,2-bis (p-chlorophenyl)-ethylene (p,p' -DDE) have been associated with type 2 diabetes mellitus (T2DM) in recent epidemiological studies. We have analysed 2,2',4,4',5,5' -hexachlorobiphenyl (CB-153) and p,p'-DDE in 544 serum-samples from Swedish women with a median age of 50 years. The participants were asked if they had diabetes and if so, what type of diabetes, years since diagnosis and what kind of treatment they had. Associations between exposure and T2DM were analysed by logistic regression. Moreover, trends of T2DM prevalence were tested with Jonckheere-Terpstrá test. Sixteen of the 544 women (3%) had diabetes, of which 15 were classified as T2DM. There was a significant association with T2DM for both CB-153 (an increase of 100 ng/g lipid corresponded to an odds ratio [OR] of 1. 6, 95% confidence interval [CI] 1. 0, 2. 7) and p,p9-DDE (OR 1. 3, 95%CI 1. 1, 1. 6). In addition, significant positive trends between quartiles of CB-153 and T2DM (P 5 0. 004) and p,p9-DDE and T2DM (P 5 0. 002) were observed. The study shows an association between POP serum concentrations and an increased prevalence of T2DM.

An increased micronucleus frequency in peripheral blood lymphocytes predicts the risk of cancer in humans.

The frequency of micronuclei (MN) in peripheral blood lymphocytes (PBL) is extensively used as a biomarker of chromosomal damage and genome stability in human populations. Much theoretical evidence has been accumulated supporting the causal role of MN induction in cancer development, although prospective cohort studies are needed to validate MN as a cancer risk biomarker. A total of 6718 subjects from of 10 countries, screened in 20 laboratories for MN frequency between 1980 and 2002 in ad hoc studies or routine cytogenetic surveillance, were selected from the database of the HUman MicroNucleus (HUMN) international collaborative project and followed up for cancer incidence or mortality. To standardize for the inter-laboratory variability subjects were classified according to the percentiles of MN distribution within each laboratory as low, medium or high frequency. A significant increase of all cancers incidence was found for subjects in the groups with medium (RR=1.84; 95% CI: 1.28-2.66) and high MN frequency (RR=1.53; 1.04-2.25). The same groups also showed a decreased cancer-free survival, i.e. P=0.001 and P=0.025, respectively. This association was present in all national cohorts and for all major cancer sites, especially urogenital (RR=2.80; 1.17-6.73) and gastro-intestinal cancers (RR=1.74; 1.01-4.71). The results from the present study provide preliminary evidence that MN frequency in PBL is a predictive biomarker of cancer risk within a population of healthy subjects. The current wide-spread use of the MN assay provides a valuable opportunity to apply this assay in the planning and validation of cancer surveillance and prevention programs.

Weight and height at 4 and 7 years of age in children born to mothers with a high intake of fish contaminated with persistent organochlorine pollutants.

In Sweden the main exposure route for persistent organochlorine pollutants (POP) is through consumption of fatty fish from the Baltic Sea (off the eastern coast). The present study aimed to investigate whether intrauterine exposure for POP may have negative impact on children's weight and height at 4 and 7 years of age, respectively. The study included 174 fishermen's wives from the Swedish east coast who had given birth to an infant with either low (n=55) or normal (n=119) birth weight, and 88 and 206 corresponding women from the Swedish west coast (where the fish is less polluted). Comparisons between the east and west coast cohorts were performed. In addition, blood samples were collected among the east coast women and the concentrations of 2,2',4,4',5,5'-hexachlorobiphenyl (CB-153) in plasma was analyzed and estimated for the year of childbirth. There were no significant differences between the east and west coast cohorts regarding weight and height at 4 and 7 years of age. There were, however, significant negative associations between the estimated plasma concentrations of CB-153 during year of childbirth and weight at 4 and 7 years of age, respectively, among the normal birth weight children. The study gives only very weak support for the hypothesized association.

Semen quality in relation to xenohormone and dioxin-like serum activity among Inuits and three European populations.

BACKGROUND: Semen quality in humans may be influenced by exposure to endocrine-disrupting compounds. OBJECTIVES: We analyzed associations between semen characteristics and serum xenoestrogen receptor (XER), xenoandrogen receptor (XAR), and aryl hydrocarbon receptor (AhR) transactivity. XER and XAR activity were measured in serum samples cleared for endogenous steroid hormones and AhR activity in raw lipophilic serum extracts free of proteins. RESULTS: All together, 319 men from Warsaw (Poland), Greenland, Kharkiv (Ukraine), and Sweden provided semen and blood samples. No strong and consistent associations between xenobiotic activity and semen quality measures were observed in the four populations. However, when the data were combined across populations sperm concentration increased 40% per unit increase in XER activity [95% confidence interval (CI), 1-79%] in the subgroup with XER activity below the reference level. Among subjects with XER activity above the reference level an increase of 14% (95% CI, 2-28%) was found. Furthermore, an increase of 10% motile sperm per unit increase in XER activity below reference level (95% CI, 0.2-20) was found. We are unable to exclude that the associations are chance findings. CONCLUSION: Alteration of XER, XAR, or AhR transactivity within the range found in serum from the general European and Inuit population seems not to markedly deteriorate sperm cell concentration, motility, or morphology in adult men.

Xenoandrogenic activity in serum differs across European and Inuit populations.

BACKGROUND: Animal and in vitro studies have indicated that human male reproductive disorders can arise as a result of disrupted androgen receptor (AR) signalling by persistent organic pollutants (POPs). Our aim in the present study was to compare serum xenoandrogenic activity between study groups with different POP exposures and to evaluate correlations to the POP proxy markers 2,2',4,4',5,5'-hexachlorobiphenyl (CB-153) and 1,1-dichloro-2,2-bis(p-chlorophenyl)-ethylene (p,p'-DDE). METHODS: We determined xenoandrogenic activity in the serum fraction containing the lipophilic POPs but free of endogenous hormones. Adult male serum (n = 261) from Greenland, Sweden, Warsaw (Poland), and Kharkiv (Ukraine) was analyzed. Xenoandrogenic activity was determined as the effect of serum extract alone (XAR) and in the presence of the synthetic AR agonist R1881 (XARcomp) on AR transactivated luciferase activity. RESULTS: The study groups differed significantly with respect to XARcomp activity, which was increased in the Inuits and decreased in the European study groups; we observed no difference for XAR activity. We found the highest level of the AR antagonist p,p'-DDE in Kharkiv, and accordingly, this study group showed the highest percent of serum samples with decreased XARcomp activities. Furthermore, the percentage of serum samples with decreased XARcomp activities followed the p,p'-DDE serum level for the European study groups. No correlations between serum XAR or XARcomp activities and the two POP markers were revealed. CONCLUSIONS: The differences in XARcomp serum activity between the study groups suggest differences in chemical exposure profiles, genetics, and/or lifestyle factors.

Hydroxy-PCBs, PBDEs, and HBCDDs in serum from an elderly population of Swedish fishermen's wives and associations with bone density.

Lack of human exposure data is frequently reported as a critical gap in risk assessments of environmental pollutants, especially regarding "new" pollutants. The objectives of this study were to assess serum levels of the persistent 2,2',4,4',5,5'-hexachlorobiphenyl (CB-153), hydroxylated polychlorinated biphenyl metabolites (OH-PCBs), polybrominated diphenyl ethers (PBDEs), and hexabromocyclodode-canes (HBCDDs) in a group of Swedish middle-aged and elderly women expected to be relatively highly exposed, and to evaluate the impact of potential determinants (e.g., fish intake, age) for the inter-individual variation, as well as to investigate the association between these pollutants and bone density. No associations were found between bone mineral density or biochemical markers of bone metabolism and the analyzed environmental pollutants. Relatively high levels of CB-153 (median 260 ng/g fat) and sigma 3-OH-PCBs (median 1.7 ng/mL serum), and low concentrations of sigma6PBDEs (median 3.6 ng/g fat) were determined. Total level of HBCDDs in serum was quantified by gas chromatography with mass spectrometric detection (median 0.5 ng/g fat). HBCDD diastereomeric and enantiomeric patterns were determined by liquid chromatography with mass spectrometric detection. The dominating stereoisomer was (-)alpha-HBCDD, but 1-3% of gamma-HBCDD was also detected in the serum samples.

Association between exposure to persistent organohalogen pollutants and epididymal and accessory sex gland function: multicentre study in Inuit and European populations.

Exposure to persistent organochlorine pollutants (POPs) may have negative impact on male reproductive function. We, therefore, investigated the association between serum levels of POPs and epididymal and accessory sex gland function. Serum levels of CB-153, p,p'-DDE and seminal markers of epididymal [neutral-alpha glucosidase (NAG)], prostatic [prostate specific-antigen (PSA)] and zinc, and seminal vesicle function (fructose) were measured from 135 Swedish fishermen and fertile men from Greenland (n=163), Warsaw, Poland (n=167) and Kharkiv, Ukraine (n=158). Multiple linear regression analyses, adjusting for potential confounders, were employed using both continuous and categorized exposure variables. Both exposure and outcome variables were log transformed. Considering the consistency between models with either continuous or categorized CB-153 levels, negative associations with the activity of NAG were found among Greenlandic men (mean difference 7.0 mU/ejaculate, 95% CI 3.0, 34), and in the aggregated cohort (mean difference 4.0 mU/ejaculate, 95% CI -0.2, 8.0). A positive association was observed between CB-153 and PSA as well as zinc among Kharkiv men. In the Swedish cohort, a negative association was found between CB-153 and fructose. In conclusion, the negative effects of POP on sperm motility, observed in the same study population might partly be caused by post-testicular mechanisms, involving a decreased epididymal function.

Autoimmune diseases, asthma and risk of haematological malignancies: a nationwide case-control study in Sweden.

To investigate potential associations between several autoimmune diseases and haematological malignancies, we studied 39,908 cases of leukaemia, Hodgkin's disease, non-Hodgkin's lymphoma and myeloma that occurred during 1987-1999 in Sweden, and 149,344 controls. Hospital discharge diagnoses of psoriasis, Sjögren's syndrome, autoimmune haemolytic anaemia, idiopathic thrombocytopenic purpura, pernicious anaemia, multiple sclerosis, rheumatic fever or asthma from 1969 to 1999 were retrieved from the Swedish Hospital Discharge Registry. Psoriasis was positively associated with leukaemia, excluding chronic lymphocytic leukaemia, (odds ratio [OR]=1.6, 95% confidence interval [CI] 1.1-2.3) and non-Hodgkin's lymphoma (OR=1.6, 95% CI 1.3-2.1). Sjögren's syndrome increased the risks of all haematological malignancies combined (OR=4.0, 95% CI 2.3-7.0), and of non-Hodgkin's lymphoma (OR=6.4, 95% CI 3.5-12). These findings, together with increased risks of several haematological malignancies in autoimmune haemolytic anaemia and idiopathic thrombocytopenic purpura but not in asthma, suggest chronic autoimmunity and immune stimulation as mechanisms contributing to the development of haematological malignancies.

Reproductive hormone levels in men exposed to persistent organohalogen pollutants: a study of inuit and three European cohorts.

OBJECTIVE: Persistent organohalogen pollutant (POP) exposure may have a negative impact on reproductive function. The objective of this study was to assess the impact of POP exposure on the male hypothalamo-pituitary-gonadal axis. PARTICIPANTS: Participants included 184 Swedish fishermen and spouses of pregnant women from Greenland (n = 258), Warsaw, Poland (n = 113) , and Kharkiv, Ukraine (n = 194). EVALUATIONS/MEASUREMENTS: Serum levels of 2,2,4,4,5,5-hexachlorobiphenyl (CB-153) and dichlorodiphenyl dichloroethene (p,p -DDE) were determined in the four populations, showing different exposure patterns: Swedish fishermen, high CB-153/low p,p -DDE; Greenland, high CB-153/high p,p -DDE; Warsaw, low CB-153/moderate p,p -DDE; Kharkiv, low CB-153/high p,p -DDE. Serum was also analyzed for testosterone, estradiol, sex hormone-binding globulin (SHBG) , inhibin B, luteinizing hormone (LH) , and follicle-stimulating hormone (FSH) . Free testosterone levels were calculated based on testosterone and SHBG. RESULTS: We found significant center-to-center variations in the associations between exposure and the outcomes. The most pronounced effects were observed in Kharkiv, where statistically significant positive associations were found between the levels of both CB-153 and p,p -DDE and SHBG, as well as LH. In Greenland, there was a positive association between CB-153 exposure and LH. In the pooled data set from all four centers, there was positive association between p,p -DDE and FSH levels [beta = 1.1 IU/L; 95% confidence interval (CI), 1.0-1.1 IU/L]. The association between CB-153 levels and SHBG was of borderline statistical significance (beta = 0.90 nmol/L; 95% CI, -0.04 to 1.9 nmol/L). CONCLUSIONS: Gonadotropin levels and SHBG seem to be affected by POP exposure, but the pattern of endocrine response is the subject of considerable geographic variation.

Semen quality and exposure to persistent organochlorine pollutants.

BACKGROUND: Inconsistent results have been found in previous human studies on male reproductive toxicity of persistent organochlorine pollutants. The majority of studies have been conducted among selected populations of infertility clients or among occupational cohorts including a limited number of participants. METHODS: We conducted a cross-sectional study of semen quality and serum concentration of 2,2',4,4',5,5'-hexachlorobiphenyl (CB-153) and 1,1-dichloro-2,2-bis (p-chlorophenyl)-ethylene (p,p'-DDE) among 763 men. We included men from all regions in Greenland (n = 194), fishermen from Sweden (n = 185), inhabitants of the city of Kharkiv, Ukraine (n = 195), and inhabitants of the city of Warsaw, Poland (n = 189). Blood samples were analyzed for CB-153 and p,p'-DDE using gas chromatography-mass spectrometry and adjusted for serum lipids. RESULTS: Sperm concentration was not impaired with increasing serum CB-153 or p,p'-DDE levels in any of the separate groups or overall. Similarly, the proportion of morphologically normal sperm was not associated with either CB-153 or p,p'-DDE blood concentration. However, sperm motility was inversely related to CB-153 concentration in Greenland and the Swedish fishermen population. Across all 4 regions, the sperm motility decreased on average by 3.6% (95% confidence interval = 1.7% to 5.6%) per one-unit increase in the log of blood CB-153 (ng/g lipid). The concentration of p,p'-DDE was negatively associated with sperm motility in the Greenlandic population and in the compiled dataset. CONCLUSION: Adult exposure to persistent organochlorine pollutants within the ranges observed in the present study is not likely to cause reduction in sperm concentration or morphology. However, higher exposure may be associated with impaired sperm motility.

Dioxin-like activities in serum across European and Inuit populations.

BACKGROUND: Persistent organic pollutants (POPs) such as polychlorinated dibenzo-p-dioxins/furans, polychlorinated biphenyls (PCBs) and organochlorine pesticides can cause a series of adverse effects on e.g. reproduction in animals and humans, many of which involve the aryl hydrocarbon receptor (AhR). The aim of the present study was to compare the integrated serum level of AhR mediated activity among European and Inuit populations, and evaluate whether the activity was associated to the selected POP markers, 2,2',4,4',5,5'-hexachlorobiphenyl (CB-153) and 1,1-dichloro-2,2-bis(p-chlorophenyl)-ethylene (p,p'-DDE). METHODS: The study included 338 males from Greenland (Inuit's), Sweden, Warsaw (Poland) and Kharkiv (Ukraine). The AhR transactivity of serum extracts alone (AhRag) and competitive AhR activity (AhRcomp) upon co-exposure with 2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD) were determined in the lipophilic serum fraction containing the POPs using the AhR mediated luciferase reporter Hepa1.12cR cell assay. RESULTS: The European groups showed higher median level of AhR-TEQ (TCDD toxic equivalents) compared to the Inuit's, whereas higher incidence of Inuits sample further induced AhRcomp activity. Neither AhRag nor AhR-TEQ were correlated to CB-153 or p,p'-DDE for any of the study groups. Multiple regressions showed a significant heterogeneity of association between the CB-153 and the AhRcomp across the study groups, and accordingly a negative association between AhRcomp and CB-153 was found for the Kharkiv group. CONCLUSION: No consistent correlation between AhR activities and two POP markers was found. Although the difference of AhRag between European and Inuit men could not be explained by CB-153 or p,p'-DDE levels alone, we believe that the variation of AhR serum activity reflects different pattern of POP exposure, genetics and/or life style factors.

Xenoestrogenic activity in blood of European and Inuit populations.

BACKGROUND: Human exposure to persistent organic pollutants (POPs) is ubiquitous and found in all individuals. Studies have documented endocrine disrupting effects and impact on reproduction. The aim of the present study was to compare the level of xenoestrogenic activity in serum of groups with varying POP exposure, and to evaluate correlations to the POP biomarkers, 2,2',4,4',5,5'-hexachlorobiphenyl (CB-153) and 1,1-dichloro-2,2-bis (p-chlorophenyl)-ethylene (p,p'-DDE). METHODS: The study included 358 men: Greenlandic Inuit's, Swedish fishermen, and Warsaw (Poland) and Kharkiv (Ukraine) inhabitants. Xenoestrogenicity of serum extracts alone (XER) and XER competitive (XERcomp) effect on 17beta-estradiol induced estrogen receptor (ER) transactivity were assessed in the hormone free, lipophilic serum fraction containing the POPs using the MVLN human breast cancer cell line. RESULTS: No agonistic XER activity was exhibited for Inuit serum samples, while 12 - 24% of the European samples had detectable agonistic XER activity. On the contrary, 71% of Inuit serum samples antagonized XERcomp compared to 7 - 30 % in the other regions. XER and XERcomp were not or weakly correlated to the two POP markers. XER activity of Inuit samples was negatively associated to levels of CB-153 and p,p'-DDE. For the Warsaw group a positive and negative correlation between XER and p,p'-DDE and estradiol equivalence level and CB-153 levels was found. CONCLUSION: No strong consistent association between xenoestrogenic net activity and the two POP markers was found. The results showed that the selected POP markers alone can not predict the integrated xenoestrogenic serum activity. Correlations to the POP markers were found at the extreme edge; the Inuit's and Warsaw study groups eliciting high frequency of samples with ER antagonistic and agonistic activity, respectively. We suggest that the variation in xenoestrogenic serum activity reflects differences in POP exposure mixture, genetic factors and/or life style factors.

Impact of PCB and p,p'-DDE contaminants on human sperm Y:X chromosome ratio: studies in three European populations and the Inuit population in Greenland.

OBJECTIVE: Recent studies indicate that persistent organohalogen pollutants (POPs) may contribute to sex ratio changes in offspring of exposed populations. Our aim in the present study was to investigate whether exposure to 2,2 ,4,4 ,5,5 -hexachlorobiphenyl (PCB-153) and dichlorodiphenyldichloroethene (p,p -DDE) affects sperm Y:X chromosome distribution. SUBJECTS AND METHODS: We obtained semen and blood for analysis of PCB-153 and p,p -DDE levels from 547 men from Sweden, Greenland, Poland (Warsaw), and Ukraine (Kharkiv), with regionally different levels of POP exposure. The proportion of Y- and X-chromosome-bearing sperm in the semen samples was determined by two-color fluorescence in situ hybridization analysis. RESULTS: Swedish and Greenlandic men had on average significantly higher proportions of Y sperm (in both cohorts, 51.2%) and correspondingly higher lipid-adjusted concentrations of PCB-153 (260 ng/g and 350 ng/g, respectively) compared with men from Warsaw (50.3% and 22 ng/g) and Kharkiv (50.7% and 54 ng/g). In the Swedish cohort, log-transformed PCB-153 and log-transformed p,p -DDE variables were significantly positively associated with Y-chromosome fractions (p-values 0.04 and <0.001, respectively). On the contrary, in the Polish cohort PCB-153 correlated negatively with the proportion of Y-bearing fraction of spermatozoa (p=0.008). CONCLUSIONS: The present study indicates that POP exposure might be involved in changing the proportion of ejaculated Y-bearing spermatozoa in human populations. Intercountry differences, with different exposure situations and doses, may contribute to varying Y:X chromosome ratios.