Prenatal concentrations of perfluoroalkyl substances and bone health in British girls at age 17

Jeddy, Zuha; Tobias, Jonathan H; Taylor, Ethel; Northstone, Kate; Flanders, W. Dana; Hartman, Terryl J.

doi:10.1007/s11657-018-0498-5

Cited by 30 publications

(24 citation statements)

References 27 publications

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“…In the same cohort, maternal plasma PFUnDA and PFHxS concentrations have been significantly associated with decreased neonatal thigh length at birth [ 8 ]. Studies have shown associations between prenatal exposure to PFAS and bone development [ 42 , 43 ]. Our findings may point to potential pathway through placenta DNA methylation; however, the mediation analysis results were not significant.…”

Section: Discussionmentioning

confidence: 99%

Concentrations of persistent organic pollutants in maternal plasma and epigenome-wide placental DNA methylation

et al. 2020

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Background Prenatal maternal plasma persistent organic pollutant (POP) concentrations have been associated with neonatal outcomes. However, the underlying mechanisms remain unknown. Placental epigenetic mechanisms may be involved, but no prior epigenome-wide studies have investigated the impact of maternal POPs on placental DNA methylation. We studied the association between maternal plasma POP concentration in early pregnancy and epigenome-wide placental DNA methylation among 260 pregnant women from the NICHD Fetal Growth Studies. Results Our analysis focused on POPs with more than 80% plasma concentrations above the limit of quantification, including 3 organochlorine pesticides (hexachlorobenzene, trans-nonachlor, p,p’ -dichlorodiphenyldichloroethylene), 1 polybrominated diphenyl ether (PBDE 47), 3 polychlorinated biphenyls (138/158, 153, 180), and 6 poly- and perfluorinated alkyl substances (PFASs) (perfluorodecanoic acid, perfluorohexanesulfonic acid, perfluorononanoic acid, perfluorooctanesulfonic acid, perfluoroundecanoic acid (PFUnDA)). Using 5% false discovery rate, POPs were associated with a total of 214 differentially methylated CpG sites (nominal p values ranging from 2.61 × 10 −21 to 2.11 × 10 −7 ). Out of the 214 CpG sites, 24 (11%) were significantly correlated with placental expression of 21 genes. Notably, higher PFUnDA was associated with increased methylation at 3 CpG sites (cg13996963, cg12089439, cg18145877) annotated to TUSC3 , and increased methylation at those 3 CpG sites was correlated with decreased expression of TUSC3 in the placenta. Increased methylation at cg18145877 ( TUSC3 ) and decreased expression of TUSC3 were correlated with shorter birth length. Out of the 214 CpG sites, methylation at 44 CpG sites was correlated ( p value < 0.10) with at least one neonatal anthropometry measure (i.e., birth weight, birth length, and head circumference). Seven CpG sites mediated ( p value < 0.05) the association between PBDE 47 and neonatal anthropometry measures. Genes annotating the top differentially methylated CpG sites were enriched in pathways related to differentiation of embryonic cells (PBDE 47) and in pathways related to brain size and brain morphology (PFASs). Conclusions DNA methylation changes in the placenta were significantly associated with maternal plasma POPs concentration. The findings suggest that placental DNA methylation and gene expression mechanism may be involved in the prenatal toxicity of POPs and their association with neonatal anthropometry measures.

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Section: Discussionmentioning

confidence: 99%

Concentrations of persistent organic pollutants in maternal plasma and epigenome-wide placental DNA methylation

et al. 2020

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“…2016 ). Bone acquisition begins before birth ( Harrast and Kalkwarf 1998 ), but few human studies have evaluated the influence of environmental chemical exposures during gestation on bone accrual and strength later in life ( Jeddy et al. 2018 ; van Zwol-Janssens et al.…”

Section: Introductionmentioning

confidence: 99%

“…2019 ). In a prospective study of PFAS exposures during pregnancy, higher maternal serum PFAS concentrations were associated with lower whole-body bone mineral content (BMC), areal BMD (aBMD), and bone area among 17-y-old females ( Jeddy et al. 2018 ).…”

Section: Introductionmentioning

confidence: 99%

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Associations of Maternal Serum Perfluoroalkyl Substances Concentrations with Early Adolescent Bone Mineral Content and Density: The Health Outcomes and Measures of the Environment (HOME) Study

Buckley

Kuiper

Lanphear

et al. 2021

Environ Health Perspect

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Background: Per- and polyfluoroalkyl substances (PFAS) may impair bone accrual and strength via endocrine disruption and nuclear receptor agonism, but human studies are primarily of adults or cross-sectional. Objectives: We assessed associations of individual PFAS and their mixture during pregnancy with child bone mineral content (BMC) and areal bone mineral density (aBMD) at age 12 y. Methods: Among 206 mother–child pairs enrolled in a prospective cohort (2003–2006), we quantified perfluorooctanoic acid (PFOA), perfluorononanoic acid (PFNA), perfluorohexane sulfonic acid (PFHxS), and perfluorooctane sulfonic acid (PFOS) in maternal serum collected during gestation or delivery. When children were age 12 y, we performed dual energy X-ray absorptiometry and calculated BMC, aBMD, and bone mineral apparent density (BMAD) -scores for six skeletal sites. We estimated covariate-adjusted -score differences per doubling of individual PFAS using linear regression and assessed the PFAS mixture using quantile g-computation and Bayesian kernel machine regression. We explored whether associations were modified by child’s sex or mediated by whole-body lean mass. Results: In covariate-adjusted models, we found that higher maternal serum concentrations of PFOA, PFNA, and the PFAS mixture were associated with lower total hip and forearm (one-third distal radius) BMC -scores in children. Differences in forearm BMC -scores were [95% confidence interval (CI): , 0.01] and (95% CI: , ) per doubling of PFOA and PFNA, respectively, and (95% CI: , ) per quartile increase in the PFAS mixture. Child’s sex modified PFOA associations for some skeletal sites; for example, differences in spine BMAD -score per doubling were (95% CI: , ) among males and 0.07 (95% CI: , 0.30) among females (modification ). Except for PFNA among females, these associations were not mediated by whole-body lean mass. Discussion: Maternal PFAS concentrations during pregnancy may be associated with lower bone mineral accrual and strength in early adolescence. https://doi.org/10.1289/EHP9424

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“…Furthermore, experimental and human autopsy evidence suggests accumulation of PFAS in the skeleton [11][12][13] . Epidemiological studies have reported an inverse relationship between PFAS exposure and bone health [14][15][16][17][18][19] , suggesting a possible role of PFAS in the onset of osteoporosis, however the associated mechanisms are still unexplored. Because different PFASs, including PFOA, have been associated with altered sex steroid 20,21 and thyroid hormone levels [22][23][24] we hypothesized that they may also affect vitamin D metabolism.…”

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confidence: 99%

Endocrine disruption of vitamin D activity by perfluoro-octanoic acid (PFOA)

Nisio

Rocca

Toni

et al. 2020

Sci Rep

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Perfluoroalkyl substances (PFAS) are a class of compounds used in industry and consumer products. Perfluorooctanoic acid (PFOA) is the predominant form in human samples and has been shown to induce severe health consequences, such as neonatal mortality, neurotoxicity, and immunotoxicity. Toxicological studies indicate that PFAS accumulate in bone tissues and cause altered bone development. Epidemiological studies have reported an inverse relationship between PFAS and bone health, however the associated mechanisms are still unexplored. Here, we present computational, in silico and in vitro evidence supporting the interference of PFOA on vitamin D (VD). First, PFOA competes with calcitriol on the same binding site of the VD receptor, leading to an alteration of the structural flexibility and a 10% reduction by surface plasmon resonance analysis. Second, this interference leads to an altered response of VD-responsive genes in two cellular targets of this hormone, osteoblasts and epithelial cells of the colorectal tract. Third, mineralization in human osteoblasts is reduced upon coincubation of PFOA with VD. Finally, in a small cohort of young healthy men, PTH levels were higher in the exposed group, but VD levels were comparable. Altogether these results provide the first evidence of endocrine disruption by PFOA on VD pathway by competition on its receptor and subsequent inhibition of VD-responsive genes in target cells.

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Prenatal concentrations of perfluoroalkyl substances and bone health in British girls at age 17

Abstract: Prenatal concentrations of some PFAS may be associated with reduced bone mass and size in adolescent girls, although it is not clear whether these associations are driven by body size.

Cited by 30 publications

References 27 publications

Concentrations of persistent organic pollutants in maternal plasma and epigenome-wide placental DNA methylation

Concentrations of persistent organic pollutants in maternal plasma and epigenome-wide placental DNA methylation

Associations of Maternal Serum Perfluoroalkyl Substances Concentrations with Early Adolescent Bone Mineral Content and Density: The Health Outcomes and Measures of the Environment (HOME) Study

Endocrine disruption of vitamin D activity by perfluoro-octanoic acid (PFOA)

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