Fetal growth and air pollution - A study on ultrasound and birth measures.

Air pollution has been suggested to affect fetal growth, but more data is needed to assess the timing of exposure effects by using ultrasound measures. It is also important to study effects in low exposure areas to assess eventual thresholds of effects. The MAPSS (Maternal Air Pollution in Southern Sweden) cohort consists of linked registry data for around 48,000 pregnancies from an ultrasound database, birth registry and exposure data based on residential addresses. Measures of air pollution exposure were obtained through dispersion modelling with input data from an emissions database (NOx) with high resolution (100-500m grids). Air pollution effects were assessed with linear regressions for the following endpoints; biparietal diameter, femur length, abdominal diameter and estimated fetal weight measured in late pregnancy and birth weight and head circumference measured at birth. We estimated negative effects for NOx; in the adjusted analyses the decrease of abdominal diameter and femur length were -0.10 (-0.17, -0.03) and -0.13 (-0.17, -0.01)mm, respectively, per 10µg/m3 increment of NOx. We also estimated an effect of NOx-exposures on birth weight by reducing birth weight by 9g per 10µg/m3 increment of NOx. We estimated small but statistically significant effects of air pollution on late fetal and birth size and reduced fetal growth late in pregnancy in a geographic area with levels below current WHO air quality guidelines.

An efficient sampling strategy for selection of biobank samples using risk scores.

AIM: The aim of this study was to suggest a new sample-selection strategy based on risk scores in case-control studies with biobank data. METHODS: An ongoing Swedish case-control study on fetal exposure to endocrine disruptors and overweight in early childhood was used as the empirical example. Cases were defined as children with a body mass index (BMI) ⩾18 kg/m2 ( n=545) at four years of age, and controls as children with a BMI of ⩽17 kg/m2 ( n=4472 available). The risk of being overweight was modelled using logistic regression based on available covariates from the health examination and prior to selecting samples from the biobank. A risk score was estimated for each child and categorised as low (0-5%), medium (6-13%) or high (⩾14%) risk of being overweight. RESULTS: The final risk-score model, with smoking during pregnancy ( p=0.001), birth weight ( p<0.001), BMI of both parents ( p<0.001 for both), type of residence ( p=0.04) and economic situation ( p=0.12), yielded an area under the receiver operating characteristic curve of 67% ( n=3945 with complete data). The case group ( n=416) had the following risk-score profile: low (12%), medium (46%) and high risk (43%). Twice as many controls were selected from each risk group, with further matching on sex. Computer simulations showed that the proposed selection strategy with stratification on risk scores yielded consistent improvements in statistical precision. CONCLUSIONS: Using risk scores based on available survey or register data as a basis for sample selection may improve possibilities to study heterogeneity of exposure effects in biobank-based studies.

Cotinine Validation of Self-Reported Smoking During Pregnancy in the Swedish Medical Birth Register.

INTRODUCTION: Self-reported data on smoking during pregnancy from the Medical Birth Register of Sweden (MBR) are widely used. However, underreporting of such behavior may occur, leading to biases. It is of importance to validate the smoking data in the MBR. The main objective was to investigate the agreement between self-reported smoking data from the MBR and cotinine levels in maternal serum among women from the general population in the region of Skåne, Sweden. We also estimated the transfer of cotinine from mother to fetus. METHODS: From a cohort used previously to investigate the relationship between intrauterine environmental exposures and offspring neuropsychiatric outcomes, there were 204 control children retrieved from the MBR with data on maternal smoking in early pregnancy registered. Data on maternal and umbilical cord cotinine at delivery were available for these children from a regional biobank. RESULTS: There was a high agreement between cotinine levels and MBR smoking data (κ = 0.82) and a high correlation between cotinine levels in maternal and umbilical cord serum (r s = 0.90, P < .001). Of the self-reported nonsmokers, 95% (95% confidence interval: 89% to 97%) were classified as nonsmokers after cotinine measurements. CONCLUSION: In these data, we found that the agreement between mothers' self-reported smoking habits during pregnancy and their levels of serum cotinine was high, as was the transfer of cotinine from mother to fetus. This indicates that birth register data on pregnancy smoking in Sweden could be considered a valid measure.

Prenatal phthalate exposure and reproductive function in young men.

BACKGROUND: Prenatal exposure to phthalates is suggested to negatively impact male reproductive function, but human data are lacking. OBJECTIVES: To study associations between prenatal exposure to diethylhexyl phthalate (DEHP) and diisononyl phthalate (DiNP), and reproductive parameters of adolescent men. METHODS: Using linear regression models adjusted for potential confounders, we studied associations between levels of DEHP- and DiNP metabolites in maternal sera from mean 12 weeks of pregnancy, and testicular size, semen quality and reproductive hormones in 112 adolescent sons, recruited from the general population. RESULTS: Men in the highest exposure tertile of one DiNP metabolite [mono-(carboxy-iso-octyl) phthalate], compared with men in the lowest tertile had: 4.3mL (95% CI: 0.89, 7.6mL; p<0.001) lower total testicular volume; 30% (95% CI: 3.6, 63%; p=0.02) higher levels of follicle-stimulating hormone; and 0.87mL (95% CI: 0.28, 1.5mL; p=0.004) lower semen volume. Men in the highest exposure tertile of one DEHP metabolite [mono-(2-ethyl-5-hydroxylhexyl) phthalate] had 0.70mL (95% CI: 0.090, 1.3mL; p=0.03) lower semen volume than men in the lowest exposure tertile. The levels of two DiNP metabolites [mono-(hydroxy-iso-nonyl) phthalate and mono-(oxo-iso-nonyl) phthalate] were linearly associated with luteinizing hormone (p<0.01). CONCLUSION: Prenatal levels of some metabolites of DEHP and DiNP seemed negatively associated with reproductive function of adolescent men.

Manganese and selenium concentrations in umbilical cord serum and attention deficit hyperactivity disorder in childhood.

Existing evidence on the effects of manganese and selenium during fetal life on neurodevelopmental disorders is inadequate. This study aims to investigate the hypothesized relationship between fetal exposure to manganese and selenium and attention deficit hyperactivity disorder (ADHD) diagnosis in childhood. Children born between 1978 and 2000 with ADHD (n=166) were identified at the Department of Child and Adolescent Psychiatry in Malmö, Sweden. Controls from the same region (n=166) were selected from the Medical Birth Register and were matched for year of birth and maternal country of birth. Manganese and selenium were measured in umbilical cord serum. The median cord serum concentrations of manganese were 4.3µg/L in the cases and 4.1µg/L in the controls. The corresponding concentrations of selenium were 47 and 48µg/L. When the exposures were analyzed as continuous variables no associations between cord manganese or selenium concentration and ADHD were observed. However, children with selenium concentrations above the 90th percentile had 2.5 times higher odds (95% confidence interval 1.3-5.1) of having ADHD compared to those with concentrations between the 10th and 90th percentiles. There was no significant interaction between manganese and selenium exposure (p=0.08). This study showed no association between manganese concentrations in umbilical cord serum and ADHD. The association between ADHD diagnoses in children with relatively high cord selenium was unexpected and should be interpreted with caution.

Levels of perfluoroalkyl substances and risk of coronary heart disease: Findings from a population-based longitudinal study.

BACKGROUND: Cross-sectional studies have shown an association between exposure to perfluoroalkyl substances (PFASs) and coronary heart disease (CHD). These findings need to be evaluated in longitudinal settings. OBJECTIVES: To investigate the risk of CHD in relation to PFAS levels in a longitudinal setting among Swedish rural residents. METHODS: In a population-based prospective cohort of male farmers and rural residents recruited in 1990-1991, all men who received a CHD diagnosis between 1992 and 2009 were identified from national registers (n=253). For each CHD case, one control, matched for age, was chosen randomly from the cohort. For all cases and controls, levels of eight PFASs at baseline were measured in stored blood samples. In addition, for a subsample, PFAS levels were also measured in serum samples collected at a follow-up in 2002-2003. RESULTS: There were no statistically significant associations between levels of seven of the eight PFASs at baseline and risk for developing CHD. There was a significant association between perfluoroheptanoic acid (PFHpA) and CHD (OR=2.72; 95% CI: 1.52, 4.84) for the 3rd quartile and (OR=2.45; 95% CI: 1.40, 4.29) for the 4th quartile compared to the lowest quartile. Changes in levels of PFCs between baseline and follow-up did not differ systematically between cases and controls. CONCLUSIONS: This longitudinal study does not lend support to the previously reported cross-sectional relationship between PFAS levels and CHD risk. We found a significant association with PFHpA, but this could be a chance finding, considering its chemical resemblance to other PFASs.

Maternal exposure to air pollution and type 1 diabetes--Accounting for genetic factors.

BACKGROUND: Genetic and non-genetic factors probably act together to initiate and accelerate development of type 1 diabetes [T1D]. One suggested risk factor contributing to development of T1D is air pollution. OBJECTIVE: The aim of the study was to investigate whether maternal exposure during pregnancy to air pollution, measured as nitrogen oxides [NOx] and ozone, in a low-dose exposure area was associated with the child developing T1D. METHOD: In Scania (Skåne), the most southern county in Sweden, 84,039 infants were born during the period 1999-2005. By the end of April 2013, 324 of those children had been diagnosed with T1D. For each of those T1D children three control children were randomly selected and matched for HLA genotype and birth year. Individually modelled exposure data at residence during pregnancy were assessed for nitrogen oxides [NOx], traffic density and ozone. RESULTS: Ozone as well as NOx exposures were associated with T1D. When the highest exposure group was compared to the lowest group an odds ratios of 1.62 (95% confidence interval [CI] 0.99-2.65) was observed for ozone in the second trimester and 1.58 (95% CI 1.06-2.35) for NOx in the third trimester. CONCLUSION: This study indicates that living in an area with elevated levels of air pollution during pregnancy may be a risk factor for offspring T1D.

Pregnancy serum concentrations of perfluorinated alkyl substances and offspring behaviour and motor development at age 5-9 years--a prospective study.

BACKGROUND: In animal studies, perfluorinated alkyl substances affect growth and neuro-behavioural outcomes. Human epidemiological studies are sparse. The aim was to investigate the association between pregnancy serum concentrations of perfluorooctanoate (PFOA) and perfluorooctane sulfonate (PFOS) and offspring behaviour and motor development at 5-9 years of age. METHODS: Maternal sera from the INUENDO cohort (2002-2004) comprising 1,106 mother-child pairs from Greenland, Kharkiv (Ukraine) and Warsaw (Poland) were analysed for PFOS and PFOA, using liquid-chromatography-tandem-mass-spectrometry. Exposures were grouped into country specific as well as pooled tertiles as well as being used as continuous variables for statistical analyses. Child motor development and behaviour at follow-up (2010-2012) were measured by the Developmental Coordination Disorder Questionnaire 2007 (DCDQ) and Strength and Difficulties Questionnaire (SDQ), respectively. Exposure-outcome associations were analysed by multiple logistic and linear regression analyses. RESULTS: In the pooled analysis, odds ratio (OR) (95% confidence interval (CI)) for hyperactivity was 3.1 (1.3, 7.2) comparing children prenatally exposed to the highest PFOA tertile with those exposed to the lowest PFOA tertile. Comparing children in the highest PFOS tertile with those in the lowest PFOS tertile showed elevated but statistically non-significant OR of hyperactivity (OR (95% CI) 1.7 (0.9, 3.2)). In Greenland, elevated PFOS was associated with higher SDQ-total scores indicating more behavioural problems (ß (95% CI)=1.0 (0.1, 2.0)) and elevated PFOA was associated with higher hyperactivity sub-scale scores indicating more hyperactive behaviour (ß (95% CI)=0.5 (0.1, 0.9)). Prenatal PFOS and PFOA exposures were not associated with motor difficulties. CONCLUSIONS: Prenatal exposure to PFOS and PFOA may have a small to moderate effect on children's neuro-behavioural development, specifically in terms of hyperactive behaviour. The associations were strongest in Greenland where exposure contrast is largest.

High in Utero Exposure to Perfluoroalkyl Substances from Drinking Water and Birth Weight: A Cohort Study among Infants in Ronneby, Sweden.

In 2013, the drinking water for one-third of the households in Ronneby, Sweden, was found to be contaminated by perfluorinated alkyl substances (PFAS, >10,000 ng/L) from Aqueous Film Forming Foam (AFFF). In utero PFAS exposure can influence birth weight, but little is known about the effects at very high levels. This study aimed to examine the association between in utero PFAS exposure and birth weight. Infants with mothers from Ronneby exposed to contaminated water at home (high exposure) and infants with mothers from Ronneby not exposed to contaminated water at home (low exposure) were compared to infants with mothers from Blekinge county excluding Ronneby (referents). All infants born in Blekinge county 1995-2013 were included (n = 30,360). Differences in birth weight were only seen among infants born after 2005. For boys, Ronneby high exposure had a lower mean birth weight than referents (-54 g, 95% CI -97; -11). For girls, Ronneby high exposure had a higher mean birth weight than referents (47 g, 95% CI 4; 90). There were no differences in birth weight between referents and Ronneby low exposure. In conclusion, high exposure to PFAS may influence birth weight in a sex-specific way, although the effect estimates were relatively small.

Intrauterine exposure to perfluorinated compounds and overweight at age 4: A case-control study.

AIMS: The aims were to investigate the association between maternal serum levels of perfluorooctane sulfonate (PFOS), perfluorooctanoic acid (PFOA), perfluorohexane sulfonate (PFHxS) and perfluorononanoic acid (PFNA) in early pregnancy and overweight in the child at 4 years and to assess potential heterogeneity in exposure effect between strata with different levels of other risk factors for overweight. METHODS: We used a case-control design and included 354 cases (ISO-BMI ≥ 18 kg/m2) and 2 controls per case (ISO-BMI ≤17 kg/m2) from child health care centers in Malmö, Sweden. Controls were selected stratified on risk scores for overweight in a propensity score framework. Maternal serum levels were analyzed in biobanked samples collected by routine around gestational week 14. Logistic regression was used to estimate odds ratios between quartiles of maternal serum levels and child overweight at age 4. RESULTS: There were no consistent monotonic exposure-response relationships. We found some significant odds ratios in specific quartiles but these were regarded as spurious findings. The absence of an effect was consistent over risk strata. CONCLUSIONS: We did not find evidence of an association between maternal serum levels of PFOS, PFOA, PFHxS and PFNA in early pregnancy and child overweight at age 4. The level of other risk factors for overweight did not affect children's susceptibility to prenatal PFAS exposure.

Exposure to polychlorinated compounds and cryptorchidism; A nested case-control study.

BACKGROUND: Maldescended testes or cryptorchidism is a genital birth defect that affects 2-9% of all male new-borns. Over the last 40 years there have been reports of increased prevalence in countries like the US, the UK and the Scandinavian countries. This possible increase has in some studies been linked to a foetal exposure to chemical pollutants. In this matched case-control study, we analysed maternal serum samples in early pregnancy for three different organochlorine compounds, to investigate whether the levels were associated with the risk of cryptorchidism. METHOD: Maternal serum samples taken during the first trimester of pregnancy from 165 cases (boys born with cryptorchidism) and 165 controls, matched for birth year and maternal age, parity and smoking habits during the pregnancy, were retrieved from the Southern Sweden Maternity Biobank. The samples were analysed for 2,2',4,4',5,5'-hexachlorobiphenyl (PCB-153), dichlorodiphenyltrichloroethane (p,p'-DDE) and hexachlorobenzene (HCB), using gas chromatography mass spectrometry. Associations between exposure and cryptorchidism were evaluated by conditional logistic regression. RESULTS: We found no statistically significantly associations between exposure to these compounds and cryptorchidism, either when the exposure variables were used as a continuous variable, or when the exposure levels were divided in quartiles. CONCLUSION: We found no evidence of an association between maternal levels of PCB-153, p,p'-DDE or HCB during the pregnancy and the risk of having cryptorchidism in the sons.

A simple and fast liquid-liquid extraction method for the determination of 2,2',4,4',5,5'-hexachlorobiphenyl (CB-153) and 1,1-dichloro-2,2-bis(p-chlorophenyl)-ethylene (p,p'-DDE) from human serum for epidemiological studies on type 2 diabetes.

A simple and fast method is presented to be used for example in studies on the relationship between serum levels of persistent organic pollutants and type 2 diabetes mellitus. Method is based on liquid-liquid extraction and gas chromatography coupled with high-resolution mass spectrometry. In the sample pre-treatment special attention was paid to minimize the number of sample manipulation steps and the amounts of organic solvents needed. Compounds analyzed were 2,2',4,4',5,5'-hexachlorobiphenyl (PCB-153) and 1,1-dichloro-2,2-bis (p-chlorophenyl)-ethylene (p,p'-DDE), the major metabolite of DDT. The method included extraction and cleanup of 0.2ml of serum in a single test tube and subsequent analysis of the extract from 0.2ml final volume. Validation was conducted to explore the performance of the method. The limits of detection for p,p'-DDE and PCB-153 based on the standard deviation of the blank samples were 4.3 and 3.1pg/ml, respectively. Repeatability was less than 2.5% at three concentration levels tested and recovery from Certified Reference Material SRM 1589a was 84% for p,p'-DDE and 87% for PCB-153 of the certified values, respectively. Serum samples from the AMAP intercalibration round 2008-2 were also analyzed, and results were 101-116% of the assigned values. The presented method was used for an epidemiological study with more than 700 serum samples from a type 2 diabetes cohort from Sweden.

Fertility and markers of male reproductive function in Inuit and European populations spanning large contrasts in blood levels of persistent organochlorines.

OBJECTIVE: We synthesized the main findings from an international epidemiologic study on the impact of biopersistent organic pollutants (POPs) on human reproductive function. DATA SOURCES AND EXTRACTION: We used a database with interview and biological data from 2,269 women and their spouses, and 18 published core papers. DATA SYNTHESIS: The study did not provide direct evidence of hormone-like activity of the polychlorinated biphenyl (PCB) congener CB-153 and the main dichlorodiphenyltrichloroethane (DDT) metabolite, 1,1-dichloro-2,2-bis(p-chlorophenyl)ethylene (p,p'-DDE), as serum concentrations of these compounds were not consistently related to either endogenous or exogenous hormone activity in serum. Nevertheless several links bewteen POP exposure and biomarkers of male reproductive function were identified. First, an association between high CB-153 serum levels and low sperm counts was detected within a subgroup of men with short androgen receptor CAG repeat length. Second, a relationship between increased CB-153 serum concentrations and decreased sperm motility was seen in all four studied regions, and indications of reduced neutral alpha-glucosidase activity in seminal plasma point to a post-testicular effect. Third, damage of sperm chromatin integrity was considerably less frequent in Greenlandic Inuits compared with that in European groups, and only in the latter was impairment of sperm chromatin integrity related to POPs. Despite these effects, fertility in terms of time taken to conceive was not related to POPs except in Inuits. A likely explanation of the latter was not identified. CONCLUSIONS: POPs may interfere with male reproductive function without major impact on fertility. The data do not provide direct evidence for endocrine disruption, hence other mechanisms should also be considered.

Reproductive toxicity of seafood contaminants: prospective comparisons of Swedish east and west coast fishermen's families.

Cohorts comprising fishermen's families on the east coast of Sweden have been found to have a high consumption of contaminated fish as well as high body burdens of persistent organochlorine pollutants (POPs). Their west coast correspondents are socio-economically similar, but with considerably lower POP exposure since the fish caught on the west coast is far less contaminated. The rationale for this was that the cohorts residing on the east coast of Sweden have been found to have a high consumption of contaminated fish as well as high body burdens of POPs, whereas their west coast correspondents are socio-economically similar, but with considerably lower POP exposure since the fish caught on the west coast is far less contaminated. Among the reproductive outcomes investigated are included both male and female parameters, as well as couple fertility and effects on the fetus. A range of exposure measures, including both questionnaire assessments of fish consumption and biomarkers, have been used. The most consistent findings of the studies are those related to the fetus, where a decreased birth weight was found across all measures of exposure, which is in agreement with studies from other populations. Some markers for male reproduction function, i.e. sperm motility, sperm chromatin integrity, and Y:X chromosome ratio, were associated with POP exposure, whereas others, such as sperm concentration and semen volume, were not. With respect to couple fertility and female reproductive parameters, no support was given for associations with POP exposure. Although some associations may have been affected by beneficial effects of essential nutrients in seafood, the overall findings are meaningful in the context of reproductive toxicity and support the usefulness of the epidemiological design.

Association between paternal smoking at the time of pregnancy and the semen quality in sons.

BACKGROUND: Maternal smoking during pregnancy has repeatedly been associated with decreased sperm counts in sons. Nevertheless, our team recently detected a lower total sperm count in the sons of smoking fathers as compared to sons of non-smoking fathers. Since paternal and maternal tobacco smoking often coincide, it is difficult to discriminate whether effects are mediated paternally or maternally when using questionnaire- or register-based studies. Therefore, getting an objective measure of the maternal nicotine exposure level during pregnancy might help disentangling the impact of paternally and maternally derived exposure. OBJECTIVES: Our aim was to study how paternal smoking at the time of the pregnancy was associated with semen quality in the sons after adjusting for the maternal levels of nicotine exposure during pregnancy. METHODS: We recruited 104 men (17-20 years old) from the general Swedish population. The participants answered a questionnaire about paternal smoking. Associations between smoking and semen volume, total sperm count, sperm concentration, morphology and motility were adjusted for levels of the nicotine metabolite cotinine in stored maternal serum samples obtained from rubella screening between the 6th and 35th week of pregnancy. We additionally adjusted for the estimated socioeconomic status. RESULTS: After adjusting for the maternal cotinine, the men of smoking fathers had 41% lower sperm concentration and 51% lower total sperm count than the men of non-smoking fathers (p = 0.02 and 0.003, respectively). This was robust to the additional adjustment. CONCLUSIONS: Our results suggest a negative association between paternal smoking and sperm counts in the sons, independent of the level maternal nicotine exposure during the pregnancy.

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.

Dietary exposure to methyl mercury and PCB and the associations with semen parameters among Swedish fishermen.

Dietary POP exposure have shown negative effects on sperm motility and sperm chromatin integrity, as well as an increased proportion of Y-chromosome bearing sperms. However, it has been suggested that in epidemiological studies investigating persistent organochlorine pollutant (POP)-toxicity, other pollutants occurring simultaneously may carry an increased risk of effects, which may obscure a clear interpretation of the role of POP toxicity. One such pollutant is methyl mercury (MeHg), which has been found in fatty fish from the Baltic Sea and as a consequence men with a high consumption of such fish has been found to have twice the MeHg levels compared to men with a low fish consumption. The aim of the present study was to assess if exposure to MeHg affects male reproductive function, assessed by measuring human sperm motility, sperm concentration, total sperm count, sperm chromatin integrity and the proportion of Y-chromosome bearing sperms. Secondly we also investigated a possible interaction between MeHg and 2, 2', 4, 4', 5, 5'-hexachlorobiphenyl (CB-153), a biomarker for POP exposure, with respect to sperm outcome measures. Blood and semen samples were collected from 195 Swedish fishermen with a mean age of 47 (range 24-67 years). Blood levels of MeHg ranged from 0.11 to 16.59 microg/L (median 2.25 microg/L) and serum levels of CB-153 from 37 to 1460 ng/g lipid (median 190 ng/g lipid). The analyses revealed no association between MeHg and any of the outcomes investigated. Although men with low MeHg and high CB-153 had slightly higher DNA Fragmentation Index and fraction of Y-chromosome bearing sperms than men with low levels of both compounds, the effects were not statistically significant. In conclusion, we did not find any associations between MeHg exposure and semen quality or quantity in the dose range observed neither was any synergistic effects between MeHg and CB-153 noted.

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.

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.