Prenatal Exposure to Perfluorinated Compounds Affects Birth Weight Through GSTM1 Polymorphism

Kwon, Eun Jin; Shin, Joon Soo; Kim, Byungmi; Shah-Kulkarni, Surabhi; Park, Hyesook; Kho, Younglim; Park, Eun Ae; Kim, Young Ju; Ha, Eun Hee

doi:10.1097/jom.0000000000000739

Cited by 24 publications

(12 citation statements)

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“…In humans, imbalance in thyroid homeostasis is often seen in T1DM patients (hyper-as well as hypothyroidism) [60] . Further, prenatal PFUnDA-exposure was reported to be associated with lower birth weight [40] and an upregulation of immunomodulatory genes were associated with a range of prenatal PFASs exposure [53] .…”

Section: Discussionmentioning

confidence: 99%

Exposure to perfluoroundecanoic acid (PFUnDA) accelerates insulitis development in a mouse model of type 1 diabetes

et al. 2016

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Perfluoralkylated substances (PFAS) are classified as persistent, bioaccumulative and toxic substances and are widespread environmental contaminants. Humans are exposed through food, drinking water and air. We have previously reported that bisphenol A accelerates spontaneous diabetes development in non-obese diabetic (NOD) mice and observed in the present study that perfluoroundecanoic acid, PFUnDA, increased insulitis development, a prerequisite for diabetes development in NOD mice. We exposed NOD mice to PFUnDA in drinking water (3, 30 and 300 μg/l) at mating, during gestation and lactation and until 30 weeks of age. After 300 μg/l PFUnDA exposure, we report (i) increased pancreatic insulitis, (ii) increased number of apoptotic cells in pancreatic islets prior to insulitis and (iii) decreased phagocytosis in peritoneal macrophages. There was also a trend of decreased number of tissue resident macrophages in pancreatic islets prior to insulitis after exposure to 300 μg/l, and altered cytokine secretion in activated splenocytes after exposure to 3 μg/l PFUnDA. Although insulitis is a prerequisite for autoimmune diabetes, the accelerated insulitis was not associated with accelerated diabetes development. Instead, the incidence of diabetes tended to be reduced in the animals exposed to 3 and 30 μg/l PFUnDA, suggesting a non-monotonic dose response. The effects of PFUnDA exposure on increased apoptosis in pancreas and reduced macrophage function as well as accelerated insulitis development in NOD mice, may also be relevant for human insulitis. Further observational autoimmune diabetes clinical cohort studies and animal experiments for PFUnDA as well as other PFASs are therefore encouraged.

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Section: Discussionmentioning

confidence: 99%

Exposure to perfluoroundecanoic acid (PFUnDA) accelerates insulitis development in a mouse model of type 1 diabetes

et al. 2016

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“…Associations with PFASs other than PFOS and PFOA in papers reviewed for only PFOS and PFOA the EFSA CONTAM Panel 2018 Opinion Kwon et al (2016) examined associations between cord blood concentrations (median) of PFHxS (0.4 ng/mL), PFNA (0.2 ng/mL), PFDA (0.1 ng/mL), PFUnDA (0.3 ng/mL), PFDoDA (0.1 ng/mL) and PFTrDA (0.4 ng/mL) and birth weight in 268 Korean infants. Serum levels of PFHxS, PFNA, PFDA and PFUnDA were all significantly and inversely associated with birth weight.…”

Section: New Publications Not Reviewed In the Efsa Contam Panel 2018 Opinionmentioning

confidence: 99%

Risk to human health related to the presence of perfluoroalkyl substances in food

Schrenk¹,

Bignami²,

Bodin³

et al. 2020

EFS2

333

265

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The European Commission asked EFSA for a scientific evaluation on the risks to human health related to the presence of perfluoroalkyl substances ( PFAS s) in food. Based on several similar effects in animals, toxicokinetics and observed concentrations in human blood, the CONTAM Panel decided to perform the assessment for the sum of four PFAS s: PFOA , PFNA , PFH xS and PFOS . These made up half of the lower bound ( LB ) exposure to those PFAS s with available occurrence data, the remaining contribution being primarily from PFAS s with short half‐lives. Equal potencies were assumed for the four PFAS s included in the assessment. The mean LB exposure in adolescents and adult age groups ranged from 3 to 22, the 95th percentile from 9 to 70 ng/kg body weight (bw) per week. Toddlers and ‘other children’ showed a twofold higher exposure. Upper bound exposure was 4‐ to 49‐fold higher than LB levels, but the latter were considered more reliable. ‘Fish meat’, ‘Fruit and fruit products’ and ‘Eggs and egg products’ contributed most to the exposure. Based on available studies in animals and humans, effects on the immune system were considered the most critical for the risk assessment. From a human study, a lowest BMDL 10 of 17.5 ng/ mL for the sum of the four PFAS s in serum was identified for 1‐year‐old children. Using PBPK modelling, this serum level of 17.5 ng/ mL in children was estimated to correspond to long‐term maternal exposure of 0.63 ng/kg bw per day. Since accumulation over time is important, a tolerable weekly intake ( TWI ) of 4.4 ng/kg bw per week was established. This TWI also protects against other potential adverse effects observed in humans. Based on the estimated LB exposure, but also reported serum levels, the CONTAM Panel concluded that parts of the European population exceed this TWI , which is of concern.

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“…Homozygous deletion polymorphisms of GSTM1 and GSTT1 (GSTM1-null and GSTT1-null) can result in loss of function and increase the risk of faulty fetal development [12]. GSTM1/GSTT1 polymorphisms can significantly modify birth outcomes following maternal exposure to tobacco smoke [13–16], heavy metals [17], perfluorinated compounds [18], and particulate matter [19]. These polymorphisms also influence early neurodevelopment of infants born following maternal exposure to environmental tobacco smoke [6].…”

Section: Introductionmentioning

confidence: 99%

Exposure to prenatal secondhand smoke and early neurodevelopment: Mothers and Children’s Environmental Health (MOCEH) study

Lee

Hong

et al. 2019

Environ Health

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BackgroundThe association between exposure to secondhand smoke (SHS) during pregnancy and a child’s neurodevelopment has not been established yet. We explored the association between prenatal exposure to SHS and neurodevelopment at 24 months of age considering genetic polymorphism and breastfeeding in 720 mothers and their offspring enrolled in the Korean multicenter birth cohort study (Mothers and Children Environmental Health, MOCEH).MethodsWe quantified urine cotinine concentrations in mothers once from 12th to 20th gestational weeks and excluded those whose urine cotinine levels exceeded 42.7 ng/ml to represent SHS exposure in early pregnancy. Mental developmental index (MDI) and psychomotor developmental index (PDI) values were measured using the Korean version of the Bayley Scales of Infant Development II (K-BSID-II) at 24 months of age. A general linear model was used to assess the relationship between maternal urinary cotinine level and neurodevelopment.ResultsMDI scores were inversely associated with cotinine [β = − 2.73; 95% confidence interval (CI): − 5.32 to − 0.15] in children whose mothers had early pregnancy urinary cotinine levels >1.90 ng/ml. No association was evident in children whose mothers had cotinine levels ≤1.90 ng/ml. This negative association was more pronounced in children whose mothers had both Glutathione S-transferases mu 1 (GSTM1) and theta 1 (GSTT1) null type [β = − 5.78; 95% CI: -10.69 to − 0.87], but not in children whose mothers had any present type of GSTM1/GSTT1 [β = − 1.64; 95% CI: -4.79 to 1.52]. The association was no longer significant when children received breast milk exclusively for up to 6 months [β = − 0.24; 95% CI: -4.69 to 4.20] compared to others [β = − 3.75; 95% CI: -7.51 to 0.00]. No significant association was found for PDI.ConclusionsMaternal exposure to SHS during pregnancy may result in delayed MDI in early childhood. This effect might be modified by genetic polymorphism and breastfeeding behavior.Electronic supplementary materialThe online version of this article (10.1186/s12940-019-0463-9) contains supplementary material, which is available to authorized users.

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Prenatal Exposure to Perfluorinated Compounds Affects Birth Weight Through GSTM1 Polymorphism

Abstract: Our findings indicated that GSTM1 polymorphism might affect the association between exposure to PFCs and birth weight, suggesting the effect of genetic susceptibility on the relationship between prenatal PFCs exposure and birth outcomes.

Cited by 24 publications

References 50 publications

Exposure to perfluoroundecanoic acid (PFUnDA) accelerates insulitis development in a mouse model of type 1 diabetes

Exposure to perfluoroundecanoic acid (PFUnDA) accelerates insulitis development in a mouse model of type 1 diabetes

Risk to human health related to the presence of perfluoroalkyl substances in food

Exposure to prenatal secondhand smoke and early neurodevelopment: Mothers and Children’s Environmental Health (MOCEH) study

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