Peripubertal serum dioxin concentrations and subsequent sperm methylome profiles of young Russian adults.
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ABSTRACT:
SUBMITTER: Pilsner JR
PROVIDER: S-EPMC6130911 | biostudies-literature | 2018 Jun
REPOSITORIES: biostudies-literature
Publications
Peripubertal serum dioxin concentrations and subsequent sperm methylome profiles of young Russian adults.
Pilsner J Richard JR Shershebnev Alex A Medvedeva Yulia A YA Suvorov Alexander A Wu Haotian H Goltsov Andrey A Loukianov Evgeny E Andreeva Tatiana T Gusev Fedor F Manakhov Andrey A Smigulina Luidmila L Logacheva Maria M Shtratnikova Victoria V Kuznetsova Irina I Speranskiy-Podobed Peter P Burns Jane S JS Williams Paige L PL Korrick Susan S Lee Mary M MM Rogaev Evgeny E Hauser Russ R Sergeyev Oleg O
Reproductive toxicology (Elmsford, N.Y.) 20180314
<h4>Background</h4>The association of exposure to endocrine disrupting chemicals in the peripubertal period with subsequent sperm DNA methylation is unknown.<h4>Objective</h4>We examined the association of peripubertal serum 2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD) concentrations with whole-genome bisulfite sequencing (WGBS) of sperm collected in young adulthood.<h4>Methods</h4>The Russian Children's Study is a prospective cohort of 516 boys who were enrolled at 8-9 years of age and provided s ...[more]
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Project description:Dioxins, furans, and polychlorinated biphenyls (PCBs), dioxin-like and non-dioxin-like, have been linked to alterations in puberty.We examined the association of peripubertal serum levels of these compounds [and their toxic equivalents (TEQs)] with pubertal onset and maturity among Russian boys enrolled at ages 8-9 years and followed prospectively through ages 17-18 years.At enrollment, 473 boys had serum dioxin-like compounds and PCBs measured. At the baseline visit and annually until age 17-18 years, a physician performed pubertal staging [genitalia (G), pubarche (P), and testicular volume (TV)]. Three hundred fifteen subjects completed the follow-up visit at 17-18 years of age. Pubertal onset was defined as TV > 3 mL, G2, or P2. Sexual maturity was defined as TV ? 20 mL, G5, or P5. Multivariable interval-censored models were used to evaluate associations of lipid-standardized concentrations with pubertal timing.Medians (interquartile ranges) of the sum of dioxin-like compounds, TEQs, and non-dioxin-like PCBs were 362 pg/g lipid (279-495), 21.1 pg TEQ/g lipid (14.4-33.2), and 250 ng/g lipid (164-395), respectively. In adjusted models, the highest compared to lowest TEQ quartile was associated with later pubertal onset [TV = 11.6 months (95% CI: 3.8, 19.4); G2 = 10.1 months (95% CI: 1.4, 18.8)] and sexual maturity [TV = 11.6 months (95% CI: 5.7, 17.6); G5 = 9.7 months (95% CI: 3.1, 16.2)]. However, the highest compared to the lowest quartile of non-dioxin-like PCBs, when co-adjusted by TEQs, was associated with earlier pubertal onset [TV = -8.3 months (95% CI:-16.2, -0.3)] and sexual maturity [TV = -6.3 months (95% CI:-12.2, -0.3); G5 = -7.2 months (95% CI:-13.8, -0.6)]; the non-dioxin-like PCB associations were only significant when adjusted for TEQs. TEQs and PCBs were not significantly associated with pubic hair development.Our results suggest that TEQs may delay, while non-dioxin-like PCBs advance, the timing of male puberty. Citation: Burns JS, Lee MM, Williams PL, Korrick SA, Sergeyev O, Lam T, Revich B, Hauser R. 2016. Associations of peripubertal serum dioxin and polychlorinated biphenyl concentrations with pubertal timing among Russian boys. Environ Health Perspect 124:1801-1807;?http://dx.doi.org/10.1289/EHP154.
| S-EPMC5089876 | biostudies-other
Project description:Exposures to endocrine-disrupting chemicals during critical phases of testicular development may be related to poorer semen parameters. However, few studies have assessed the association between childhood organochlorine (OC) exposure and adult semen parameters.We examined whether peripubertal serum OC concentrations are associated with semen parameters among young Russian men.From 2003 through 2005, 516 boys were enrolled at age 8-9 years and followed for up to 10 years. Serum OCs were measured in the enrollment samples using high-resolution mass spectrometry. At 18-19 years, 133 young men provided 1 or 2 semen samples (256 samples) collected approximately 1 week apart, which were analyzed for volume, sperm concentration, and motility. Unadjusted and adjusted linear mixed models were used to examine the associations of quartiles of lipid-standardized concentrations of dioxins [2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD), polychlorinated dibenzo-p-dioxins (PCDDs)], furans, polychlorinated biphenyls (PCBs), and corresponding toxic equivalents (TEQs) with semen parameters.The median (range) for TCDD was 2.9 (0.4-12.1) pg/g lipid and PCDD TEQ was 8.7 (1.0-36.0) pg TEQ/g lipid. Higher quartiles of TCDD and PCDD TEQs were associated with lower sperm concentration, total sperm count, and total motile sperm count (p-trends ? 0.05). The highest quartile of peripubertal serum TCDD concentrations was associated with a decrease (95% CI) of 40% (18, 66%), 29% (3, 64%), and 30% (2, 70%) in sperm concentration, total sperm count, and total motile sperm count, respectively, compared with the lowest quartile. Similar associations were observed for serum PCDD TEQs with semen parameters. Serum PCBs, furans, and total TEQs were not associated with semen parameters.Higher peripubertal serum TCDD concentrations and PCDD TEQs were associated with poorer semen parameters. Citation: Mínguez-Alarcón L, Sergeyev O, Burns JS, Williams PL, Lee MM, Korrick SA, Smigulina L, Revich B, Hauser R. 2017. A longitudinal study of peripubertal serum organochlorine concentrations and semen parameters in young men: the Russian Children's Study. Environ Health Perspect 125:460-466;?http://dx.doi.org/10.1289/EHP25.
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Project description:Exposure to dioxins has been associated with delayed pubertal onset in both epidemiologic and animal studies. Whether genetic polymorphisms may modify this association is currently unknown. Identifying such genes could provide insight into mechanistic pathways. This is one of the first studies to assess genetic susceptibility to dioxins.We evaluated whether common polymorphisms in genes affecting either molecular responses to dioxin exposure or pubertal onset influence the association between peripubertal serum dioxin concentration and male pubertal onset.In this prospective cohort of Russian adolescent boys (n = 392), we assessed gene-environment interactions for 337 tagging single-nucleotide polymorphisms (SNPs) from 46 candidate genes and two intergenic regions. Dioxins were measured in the boys' serum at age 8-9 years. Pubertal onset was based on testicular volume and on genitalia staging. Statistical approaches for controlling for multiple testing were used, both with and without prescreening for marginal genetic associations.After accounting for multiple testing, two tag SNPs in the glucocorticoid receptor (GR/NR3C1) gene and one in the estrogen receptor-? (ESR1) gene were significant (q < 0.2) modifiers of the association between peripubertal serum dioxin concentration and male pubertal onset defined by genitalia staging, although not by testicular volume. The results were sensitive to whether multiple comparison adjustment was applied to all gene-environment tests or only to those with marginal genetic associations.Common genetic polymorphisms in the glucocorticoid receptor and estrogen receptor-? genes may modify the association between peripubertal serum dioxin concentration and pubertal onset. Further studies are warranted to confirm these findings.
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Project description:Childhood blood lead levels (BLL) have been associated with growth impairment.We assessed associations of peripubertal BLL with adolescent growth and near adult height in a longitudinal cohort of Russian boys.481 boys were enrolled at ages 8-9years and followed annually to age 18. At enrollment, BLL was measured, and height, weight, and pubertal staging were obtained annually during 10years of follow-up. Mixed effects models were used to assess the associations of BLL with longitudinal age-adjusted World Health OrganizationZ-scores for height (HT-Z) and body mass index (BMI-Z), and annual height velocity (HV). Interactions between boys' age and BLL on growth outcomes were evaluated.The median (range) BLL was 3.0 (0.5-31.0) ?g/dL. At age 18years, 79% of boys had achieved near adult height (HV <1.0cm/year), and means (SD) for HT-Z and BMI-Z were 0.15 (0.92) and -0.32 (1.24). Over 10years of follow-up, after covariate adjustment, boys with higher (?5?g/dL) BLL compared with lower BLL were shorter (adjusted mean difference in HT-Z=-0.43, 95% CI -0.60, -0.25, p-value <0.001), translating to a 2.5cm lower height at age 18years. The decrement in height for boys with higher BLL was most pronounced at 12 to 15years of age (interaction p=0.03). Boys with higher BLL were leaner (adjusted mean difference in BMI-Z=-0.22, 95% CI: -0.45, 0.01, p=0.06).Higher peripubertal BLLs were associated with shorter height through age 18years, suggesting a persistent effect of lead on linear growth.
| S-EPMC5561550 | biostudies-literature
Project description:BackgroundLimited human data suggest an association of organochlorine pesticides (OCPs) with adverse effects on children's growth.ObjectiveWe evaluated the associations of OCPs with longitudinally assessed growth among peripubertal boys from a Russian cohort with high environmental OCP levels.MethodsA cohort of 499 boys enrolled in the Russian Children's Study between 2003 and 2005 at 8-9 years of age were followed prospectively for 4 years. At study entry, 350 boys had serum OCPs measured. Physical examinations were conducted at entry and annually. The longitudinal associations of serum OCPs with annual measurements of body mass index (BMI), height, and height velocity were examined by multivariate mixed-effects regression models for repeated measures, controlling for potential confounders.ResultsAmong the 350 boys with OCP measurements, median serum hexachlorobenzene (HCB), ?-hexachlorocyclohexane (?HCH), and p,p´-dichlorodiphenyldichloroethylene (p,p´-DDE) concentrations were 159 ng/g lipid, 168 ng/g lipid, and 287 ng/g lipid, respectively. Age-adjusted BMI and height z-scores generally fell within the normal range per World Health Organization standards at entry and during follow-up. However, in adjusted models, boys with higher serum HCB, ?HCH, and p,p´-DDE had significantly lower mean [95% confidence interval (CI)] BMI z-scores, by -0.84 (-1.23, -0.46), -1.32 (-1.70, -0.95), and -1.37 (-1.75, -0.98), respectively, for the highest versus lowest quintile. In addition, the highest quintile of p,p´-DDE was associated with a significantly lower mean (95% CI) height z-score, by -0.69 (-1.00, -0.39) than that of the lowest quintile.ConclusionsSerum OCP concentrations measured at 8-9 years of age were associated with reduced growth, particularly reduced BMI, during the peripubertal period, which may affect attainment of optimal adult body mass and height.
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Project description:BackgroundFew studies have evaluated predictors of childhood exposure to organochlorine pesticides (OCPs), a class of lipophilic persistent chemicals.ObjectivesOur goal was to identify predictors of serum OCP concentrations-hexachlorobenzene (HCB), ?-hexachlorocyclohexane (?-HCH), and p,p-dichlorodiphenyldichloroethylene (p,p´-DDE)-among boys in Chapaevsk, Russia.MethodsBetween 2003 and 2005, 499 boys 8-9 years of age were recruited in a prospective cohort. The initial study visit included a physical examination; blood collection; health, lifestyle, and food-frequency questionnaires; and determination of residential distance from a local factory complex that produced HCB and ?-HCH. Fasting serum samples were analyzed for OCPs at the U.S. Centers for Disease Control and Prevention. General linear regression models were used to identify predictors of the boys' serum HCB, ?-HCH, and p,p´-DDE concentrations.ResultsAmong 355 boys with OCP measurements, median serum HCB, ?-HCH, and p,p´-DDE concentrations were 158, 167, and 284 ng/g lipid, respectively. Lower body mass index, longer breastfeeding duration, and local dairy consumption were associated with higher concentrations of OCPs. Boys who lived < 2 km from the factory complex had 64% (95% CI: 37, 96) and 57% (95% CI: 32, 87) higher mean HCB and ?-HCH concentrations, respectively, than boys who lived ? 5 km away. Living > 3 years in Chapaevsk predicted higher ?-HCH concentrations, and having parents who lacked a high school education predicted higher p,p´-DDE concentrations.ConclusionsAmong this cohort of prepubertal Russian boys, predictors of serum OCPs included consumption of local dairy products, longer local residence, and residential proximity to the local factory complex.
| S-EPMC3855511 | biostudies-literature
Project description:Dioxins, furans, and polychlorinated biphenyls (PCBs) are persistent and bioaccumulative toxic chemicals that are ubiquitous in the environment. We assessed predictors of their serum concentrations among women living in a Russian town contaminated by past industrial activity. Blood samples from 446 mothers aged 23-52 years were collected between 2003-2005 as part of the Russian Children's Study. Serum dioxin, furan, and PCB concentrations were quantified using high-resolution gas chromatography-mass spectrometry. Potential determinants of exposure were collected through interviews. Multivariate linear regression models were used to identify predictors of serum concentrations and toxic equivalencies (TEQs). The median total PCB concentrations and total TEQs were 260 ng/g lipid and 25 pg TEQ/g lipid, respectively. In multivariate analyses, both total PCB concentrations and total TEQs increased significantly with age, residential proximity to a local chemical plant, duration of local farming, and consumption of local beef. Both decreased with longer breastfeeding, recent increases in body mass index, and later blood draw date. These demographic and lifestyle predictors showed generally similar associations with the various measures of serum dioxins, furans, and PCBs.
| S-EPMC3128795 | biostudies-literature
Project description:Background2,3,7,8-Tetrachlorodibenzo-p-dioxin (TCDD), a widespread environmental contaminant, is a known endocrine disruptor. In animal studies, TCDD exposure impairs bone metabolism and increases fragility. To our knowledge, no epidemiologic studies have examined this association.ObjectivesOn 10 July 1976, a chemical explosion in Seveso, Italy, resulted in the highest known residential exposure to TCDD. In 1996, we initiated the Seveso Women's Health Study, a retrospective cohort study of the health of the women. In 2008, we followed up the cohort. Here, we evaluated the association between TCDD exposure and bone structure and geometry in adulthood, and considered whether timing of TCDD exposure before achievement of peak bone mass (assumed to occur 2 years after onset of menarche) modified the association.MethodsIndividual TCDD concentration was measured in archived serum collected soon after the explosion. In 2008, 350 women who were <20 years old in 1976 underwent a dual-energy X-ray absorptiometry (DXA) bone scan. Bone mineral density was measured at the lumbar spine and hip, and hip geometry was extracted from hip DXA scans using the hip structural analysis method.ResultsAmong premenopausal women, TCDD serum levels were associated with some indexes indicating better bone structure in women exposed before peak bone mass (n=219), with stronger associations in those exposed before 5 years of age (n=46). In contrast, among postmenopausal women, TCDD levels were associated with evidence of better bone structure in women exposed after peak bone mass (n=48) than in other women (n=18).ConclusionsOur current results do not support the hypothesis that postnatal TCDD exposure adversely affects adult bone health. Continued follow-up of women who were youngest at exposure is warranted. Future studies should also focus on those exposed in utero.
| S-EPMC3888571 | biostudies-literature
Project description:BackgroundDioxins, furans and polychlorinated biphenyls (PCBs) are endocrine disruptors with half-lives of months to years in humans. Peripubertal exposure to these chemicals may disrupt pubertal timing. Biomarker exposure metrics like the sum of non-dioxin-like PCBs in serum (∑NDL-PCBs) involve chemicals with different hypothetical effects. Empirical exposure metrics represent an alternative that requires no knowledge of biological mechanisms.MethodsFrom 2003 to 2005, 516 Russian boys aged 8-9 residing near a plant that historically produced organochlorine pesticides were enrolled in the Russian Children's Study. At enrollment, blood was collected for measurement of organochlorine chemicals by the Centers for Disease Control and Prevention (CDC). Variable cluster analysis was used to empirically group serum levels of 45 dioxins, furans and PCBs into eight cluster scores. These scores were compared to the sum of dioxin-like toxic equivalents (∑TEQs) and ∑NDL-PCBs using Spearman correlation coefficients.ResultsClustering appeared to reflect number and position of chlorine atoms. Clusters 4, 7 and 1 contained, respectively, tri/tetra-, tetra/penta-, and hexa/hepta-chlorinated PCBs with chlorines at the 4,4' positions. Clusters 2, 8 and 5 contained, respectively, tetra-to hexa-, hexa/hepta-, and hepta/octa-chlorinated PCBs with chlorines at the 2,2' positions. ∑NDL-PCBs were highly correlated with 4,4'-chlorinated clusters 1 and 7 (Spearman's ρ = 0.8) and less so with all other clusters (Spearman's ρ = 0.4-0.5).ConclusionsIn this cohort of Russian boys, baseline serum dioxins, furans and PCBs seemed to cluster by chlorination pattern, possibly reflecting shared persistence, metabolism or source of exposure. The widely used measure ∑NDL-PCB seemed most representative of 4,4'-chlorinated PCBs.
| S-EPMC8594624 | biostudies-literature
Project description:2,3,7,8-Tetrachlorodibenzo-p-dioxin (TCDD) is a persistent environmental contaminant. Although experimental evidence suggests that TCDD alters thyroid hormone levels in rodents, human data are inconsistent. In 1976, a trichlorophenol plant exploded in Seveso, Italy. Women living in highly exposed areas were followed through the Seveso Women's Health Study. TCDD concentrations were measured in 1976 (n = 981) and 1996 (n = 260), and levels of total thyroxine, free thyroxine, free triiodothyronine, and thyroid-stimulating hormone were measured in 1996 (n = 909) and 2008 (n = 724). We used conditional multiple linear regression and marginal structural models with inverse-probability-of-treatment weights to evaluate associations and causal effects. TCDD concentration in 1976 was inversely associated with total thyroxine level in 1996 but not in 2008. Associations were stronger among women who had been exposed before menarche. Among these women, associations between total thyroxine and concurrent 1996 TCDD were slightly weaker than those with 1976 TCDD. A model including both 1976 and 1996 measurements strengthened the relationship between 1976 TCDD and total thyroxine but drove the association with 1996 TCDD to the null. TCDD exposure was not associated with levels of other thyroid hormones. TCDD exposure, particularly exposure before menarche, may have enduring impacts on women's total thyroxine levels. Initial exposure appears to be more influential than remaining body burden.
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