Dataset Information

Dioxin exposure and age of pubertal onset among Russian boys.

ABSTRACT:

Background

Animal data demonstrate associations of dioxin, furan, and polychlorinated biphenyl (PCB) exposures with altered male gonadal maturation. It is unclear whether these associations apply to human populations.

Objectives

We investigated the association of dioxins, furans, PCBs, and corresponding toxic equivalent (TEQ) concentrations with pubertal onset among boys in a dioxin-contaminated region.

Methods

Between 2003 and 2005, 499 boys 8-9 years of age were enrolled in a longitudinal study in Chapaevsk, Russia. Pubertal onset [stage 2 or higher for genitalia (G2+) or testicular volume (TV) > 3 mL] was assessed annually between ages 8 and 12 years. Serum levels at enrollment were analyzed by the Centers for Disease Control and Prevention, Atlanta, Georgia, USA. We used Cox proportional hazards models to assess age at pubertal onset as a function of exposure adjusted for potential confounders. We conducted sensitivity analyses excluding boys with pubertal onset at enrollment.

Results

The median (range) total serum TEQ concentration was 21 (4-175) pg/g lipid, approximately three times higher than values in European children. At enrollment, boys were generally healthy and normal weight (mean body mass index, 15.9 kg/m2), with 30% having entered puberty by G2+ and 14% by TV criteria. Higher dioxin TEQs were associated with later pubertal onset by TV (hazard ratio = 0.68, 95% confidence interval, 0.49-0.95 for the highest compared with the lowest quartile). Similar associations were observed for 2,3,7,8-tetrachlorodibenzo-p-dioxin and dioxin concentrations for TV but not G2+. Results were robust to sensitivity analyses.

Conclusions

Findings support an association of higher peripubertal serum dioxin TEQs and concentrations with later male pubertal onset reflected in delayed testicular maturation.

SUBMITTER: Korrick SA

PROVIDER: S-EPMC3230396 | biostudies-literature | 2011 Sep

REPOSITORIES: biostudies-literature

ACCESS DATA

Publications

Dioxin exposure and age of pubertal onset among Russian boys.

Korrick Susan A SA Lee Mary M MM Lee Mary M MM Williams Paige L PL Sergeyev Oleg O Burns Jane S JS Patterson Donald G DG Turner Wayman E WE Needham Larry L LL Altshul Larisa L Revich Boris B Hauser Russ R

Environmental health perspectives 20110428 9

<h4>Background</h4>Animal data demonstrate associations of dioxin, furan, and polychlorinated biphenyl (PCB) exposures with altered male gonadal maturation. It is unclear whether these associations apply to human populations.<h4>Objectives</h4>We investigated the association of dioxins, furans, PCBs, and corresponding toxic equivalent (TEQ) concentrations with pubertal onset among boys in a dioxin-contaminated region.<h4>Methods</h4>Between 2003 and 2005, 499 boys 8-9 years of age were enrolled ...[more]

PMID: 21527364

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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.

Project description:Study questionIs the age of onset of pubertal markers related to subsequent changes in DNA methylation (DNAm)?Summary answerWe identified 273 cytosine-phosphate-guanine (CpG) dinucleotides in girls and 67 CpGs in boys that were related to puberty and that were replicable in two other investigations.What is known alreadyPreviously, 457 CpGs (not gender-specific) and 347 (in girls) and 50 (in boys), respectively, were found to be associated with puberty, according to investigations of studies from Denmark (20 girls and 31 boys) and North America (30 girls and 25 boys).Study design size durationThe study was based on a birth cohort of 1456 participants born in 1989/90, with follow-up at age 10 and 18 years.Participants/materials setting methodsThe follow-up included 470 participants with information on DNAm and age of pubertal onset (244 girls and 226 boys). Age of pubertal onset was ascertained retrospectively at age 18 years. Using the Pubertal Development Scale, both genders were asked about ages of onset of growth spurt, body hair growth and skin changes. Ages at voice deepening and growth of facial hair were inquired from boys; ages at breast development and menarche from girls. Blood samples were collected at 10 and 18 years of age. DNA was extracted using a standard salting out procedure. The methylation level for each CpG site was assessed using one of two different platforms. DNAm was measured by a ratio of intensities denoted as β values for each CpG site. After quality control, 349 455 CpG sites were available for analysis. M values were calculated (log2(β/(1-β)) to approximate a normal distribution, and their levels were adjusted for blood cell proportions. Linear mixed models were applied to test the association between age of pubertal markers and repeated measurement of DNAm at 10 and 18 years.Main results and the role of chanceIn girls, a total of 63 019 CpGs statistically significantly changed after occurrence of any of the five pubertal events and 13 487 were changed subsequent to all five events: the respective number is boys were 3072 and 301. To further exclude false-positive findings, we investigated which CpGs were replicable in prior studies from Denmark or North America, resulting in 273 replicable CpG in girls and 67 CpGs in boys (236 and 68 genes, respectively). Most identified genes are known to be related to biological processes of puberty; however, genetic polymorphisms of only four of these genes were previously linked to pubertal markers in humans.Limitations reasons for cautionThe relative age of pubertal onset to the age of DNAm measurements does not allow causal inference, since DNAm at an earlier age may have affected the pubertal age or pubertal age may have altered later DNAm. This investigation concentrates on autosomes. CpGs on X and Y chromosomes are not included in the current study.Wider implications of the findingsAssessment of biological processes involved in pubertal transitions should include epigenetic information. Differential DNAm related to puberty needs to be investigated to determine whether it can act as an early marker for adult diseases known to be associated with puberty.Study funding/competing interestsThis work was supported by NIH grants R03HD092776 (Epigenetic characterization of pubertal transitions) and R01AI121226. The 10-year follow-up of this study was funded by National Asthma Campaign, UK (Grant No 364), and the 18-year follow-up by a grant from the National Heart and Blood Institute (R01 HL082925). The authors have no conflicts to report.

Project description:BackgroundFew human studies have evaluated the impact of childhood exposure to organochlorine pesticides (OCP) on pubertal development.ObjectiveWe evaluated associations of serum OCP concentrations [hexachlorobenzene (HCB), ?-hexachlorocyclohexane (?HCH), and p,p-dichlorodiphenyldichloroethylene (p,p´-DDE)] with age at attainment of sexual maturity among boys.MethodsFrom 2003 through 2005, 350 8- to 9-year-old boys from Chapaevsk, Russia, with measured OCPs were enrolled and followed annually for 8 years. We used multivariable interval-censored models to evaluate associations of OCPs (quartiles) with three physician-assessed measures of sexual maturity: Tanner stage 5 for genitalia growth, Tanner stage 5 for pubic hair growth, or testicular volume (TV) ? 20 mL in either testis.ResultsIn adjusted models, boys with higher HCB concentrations achieved sexual maturity reflected by TV ? 20 mL a mean of 3.1 months (95% CI: -1.7, 7.8), 5.3 months (95% CI: 0.6, 10.1), and 5.0 months (95% CI: 0.2, 9.8) later for quartiles Q2, Q3, and Q4, respectively, compared with Q1 (p trend = 0.04). Tanner stage 5 for genitalia growth was attained a mean of 2.2 months (95% CI: -3.1, 7.5), 5.7 months (95% CI: 0.4, 11.0), and 3.7 months (95% CI: -1.7, 9.1) later for quartiles Q2, Q3, and Q4, respectively, of ?HCH compared with Q1 (p trend = 0.09). Tanner stage 5 for pubic hair growth occurred 6-9 months later on average for boys in the highest versus lowest quartile for HCB (p trend < 0.001), ?HCH (trend p = 0.01), and p,p´-DDE (p trend = 0.04). No associations were observed between p,p´-DDE and Tanner stage 5 for genitalia growth or TV ? 20 mL.Conclusions and relevanceHigher prepubertal serum HCB and ?HCH concentrations were associated with a later age at attainment of sexual maturity. Only the highest quartile of serum p,p´-DDE was associated with later pubic hair maturation.CitationLam T, Williams PL, Lee MM, Korrick SA, Birnbaum LS, Burns JS, Sergeyev O, Revich B, Altshul LM, Patterson DG Jr, Hauser R. 2015. Prepubertal serum concentrations of organochlorine pesticides and age at sexual maturity in Russian boys. Environ Health Perspect 123:1216-1221; http://dx.doi.org/10.1289/ehp.1409022.

Project description:BackgroundChildhood exposure to organochlorines has been associated with alterations in somatic growth. We evaluated the associations of peri-pubertal serum levels of dioxin-like compounds (DLCs) and nondioxin-like polychlorinated biphenyls (NDL-PCBs), with adolescent growth, body composition, and near adult height (NAH) in a longitudinal cohort study of Russian boys.Methods473 8-9 year-old boys had serum DLCs and associated toxic equivalents (TEQs) and NDL-PCBs concentrations measured. Physical examinations were performed at enrollment between 2003 and 2005, and annually over 11 years to 2016; annual bio-electric impedance analysis (BIA) of body composition began in 2006. We used mixed effects models to evaluate associations of quartiles of serum chemical concentrations with longitudinal measurements through age 19 of body mass index (BMI-Z) and height (HT-Z) z-scores, annual height velocity (HV), and BIA-derived height-adjusted fat (FMi) and fat-free mass (FFMi) indexes. Potential modification by age of the associations of chemical exposures with growth was evaluated. NAH (defined as HV < 1 cm/year) and age at NAH attainment were estimated using parametric survival models accounting for right censoring.ResultsThe medians of serum ∑TEQs, ∑DLCs, and ∑NDL-PCBs were 21.1 pg TEQ/g lipid, 362 pg/g lipid, and 250 ng/g lipid, respectively. In multivariable models, higher serum concentrations of peri-pubertal ∑TEQs, ∑DLCs, and ∑NDL-PCBs were associated with significantly lower BMI-Z, FMi, and FFMi over 11 years of follow-up. The differences in FFMi for boys with higher versus lower ΣTEQs and ΣNDL-PCBs increased with age. In multivariable models, higher ∑NDL-PCBs were associated with lower HT-Z, with attenuation of the association with age (interaction p < 0.001). The highest versus the lowest quartiles of ∑NDL-PCBs were not associated with differences in NAH, but were associated with an average of 6 months later attainment of NAH.ConclusionsOur findings suggest that dioxin and NDL-PCB exposures during childhood are associated with alterations in body composition and subsequent somatic growth.

Dataset Information

Dioxin exposure and age of pubertal onset among Russian boys.

Background

Objectives

Methods

Results

Conclusions

Publications

Dioxin exposure and age of pubertal onset among Russian boys.

Similar Datasets

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