Transcriptional changes in steroidogenesis by perfluoroalkyl acids (PFOA and PFOS) regulate the synthesis of sex hormones in H295R cells

Kang, Jae Soon; Choi, Jinsoo; Park, June-Woo

doi:10.1016/j.chemosphere.2016.04.070

Cited by 81 publications

(35 citation statements)

References 44 publications

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“…Furthermore, PFOS as potential endocrine disrupting chemical was also related to the transcriptional induction gene cyp11b2 (encoding CYP11B2, aldosterone synthetase). Aldosterone is involved in blood pressure regulation by increasing the reuptake of ions and water in the kidneys [42].…”

Section: Discussionmentioning

confidence: 99%

Perfluoroalkyl substances are associated with elevated blood pressure and hypertension in highly exposed young adults

Pitter

Jeddi

Barbieri

et al. 2020

Preprint

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BackgroundResidents in a large area of North-Eastern Italy were exposed to perfluoroalkyl substances (PFAS) via drinking water. Studies on the association between PFAS and blood pressure levels are limited, and results are inconsistent. Using cross-sectional data from the Regional health surveillance program, we aimed to quantify the associations between PFAS serum concentrations and blood pressure and hypertension prevalence.MethodsThe study comprised 16,224 individuals aged 20-39 years. Pregnant women (n=327), or individuals with missing information on the selected covariates (n=111) were excluded, leaving 15,786 subjects for the analyses. Hypertension was defined as any self-reported diagnosis, use of antihypertensive drugs, or elevated systolic blood pressure (SBP≥140 mmHg)/diastolic blood pressure (DBP≥90 mmHg). Generalized additive models were used to investigate the relation between perfluorooctanoic acid (PFOA), perfluorooctane sulfonic acid (PFOS), perfluorohexane sulfonic acid (PFHxS), and perfluorononanoic acid (PFNA)) natural log (ln) transformed and by decile, and SBP, DBP, hypertension, adjusted for potential confounders.ResultsBoth SBP and DBP increased significantly with an increase in the ln-transformed serum PFAS concentrations in a monotonic way. The predicted increase in SBP and DBP were 1.54 mmHg (95%CI 0.61-2.47), 1.60 mmHg (95%CI 0.92-2.27) from lowest to highest decile of PFOA. The associations were stronger for SBP in men and for DBP in women. One unit increase in each In-transformed PFAS was positively associated with an increased odd of hypertension in men: PFOA OR=1.06 (1.01-1.11), PFOS OR=1.13 (1.03-1.23), PFHxS OR=1.08 (1.02-1.15), PFNA OR=1.20 (1.02-1.40).ConclusionsOur findings suggest that serum PFAS concentrations were associated with increased systolic and diastolic blood pressure in a large highly exposed young adult population. Although the magnitude of the observed effect was relatively small, if confirmed it would be of public health relevance since even small increases in blood pressure levels at the population level may be associated to a raised risk of adverse outcomes such as cardiovascular disease and target organ damage.

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Section: Discussionmentioning

confidence: 99%

Perfluoroalkyl substances are associated with elevated blood pressure and hypertension in highly exposed young adults

Pitter

Jeddi

Barbieri

et al. 2020

Preprint

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“…PFOA is a PPARα activator, and modifies genes that function in steroidogenesis, leading to diverse endocrine effects [60, 61], negatively affects thyroid function, and leads to an oxidative stress response and inflammatory response [62]. PFOA treatment increased the expression of 12 genes (11 ≥ 1.5-fold and 6 ≥ 2-fold) and decreased the expression of 43 genes (18 ≥ 1.5-fold, 5 ≥ 2-fold, and 1 ≥ 4-fold) (Table S4).…”

Section: Resultsmentioning

confidence: 99%

Effects of long-term endocrine disrupting compound exposure on Macaca mulatta embryonic stem cells

Midic

Vincent

VandeVoort

et al. 2016

Reproductive Toxicology

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Endocrine disrupting chemicals (EDCs) exert significant effects on health and physiology, many traceable to effects on stem cell programming underlying development. Understanding risk of low-level, chronic EDC exposure will be enhanced by knowledge of effects on stem cells. We exposed rhesus monkey embryonic stem cells to low levels of five EDCs [bisphenol A (BPA), atrazine (ATR), tributyltin (TBT), perfluorooctanoic acid (PFOA), and di-(2-ethylhexyl) phthalate (DEHP)] for 28 days, and evaluated effects on gene expression by RNAseq transcriptome profiling. We observed little effect of BPA, and small numbers of affected genes (≤119) with other EDCs. There was substantial overlap in effects across two, three, or four treatments. Ingenuity Pathway analysis indicated suppression of cell survival genes and genes downstream of several stress response mediators, activation of cell death genes, and modulations in several genes regulating pluripotency, differentiation, and germ layer development. Potential adverse effects of these changes on development are discussed.

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“…Furthermore, PFOS as potential endocrine disrupting chemical was also related to the transcriptional induction gene cyp11b2 (encoding CYP11B2, aldosterone synthetase). Aldosterone is related to regulating blood pressure by increasing the reuptake of ions and water in the kidneys [40].…”

Section: Discussionmentioning

confidence: 99%

Perfluoroalkyl Substances Are Associated With Elevated Blood Pressure and Hypertension in Highly Exposed Young Adults

Pitter

Jeddi

Barbieri

et al. 2020

Preprint

View full text Add to dashboard Cite

Background Residents in a large area of North-Eastern Italy were exposed to perfluoroalkyl substances (PFAS) via drinking water. Studies on the association between PFAS and blood pressure levels are limited and results inconsistent. Using cross-sectional data from the Regional health surveillance program, we aimed to quantify the associations between PFAS serum concentrations and blood pressure and hypertension prevalence. Methods The study included 16,224 individuals aged 20-39 years. Pregnant women (n=327), or individuals with missing information on the selected covariates (n=111) were excluded, leaving 15,786 subjects. Hypertension was defined as any self-reported diagnosis, use of antihypertensive drugs, or elevated systolic blood pressure (SBP)/diastolic blood pressure (DBP). Generalized additive models were used to investigate the relation between each PFAS (perfluorooctanoic acid (PFOA), perfluorooctane sulfonic acid (PFOS), perfluorohexane sulfonic acid (PFHxS), and perfluorononanoic acid (PFNA)) ln transformed and by decile, and SBP, DBP, hypertension, adjusted for potential confounders. Results Both SBP and DBP increased significantly with an increase in the ln-transformed serum PFAS concentrations in a monotonic way. The predicted increase in SBP and DBP were 1.54 mmHg (95%CI 0.61-2.47), 1.60 mmHg (95%CI 0.92-2.27) from lowest to highest decile of PFOA. The associations were stronger for SBP in men and DBP in women. One unit increase in each natural log transformed PFAS was positively associated with an increased odd of hypertension in men: PFOA OR=1.06 (1.01-1.11), PFOS OR=1.13 (1.03-1.23), PFHxS OR=1.08 (1.02-1.15), PFNA OR=1.20 (1.02-1.40). Conclusions Our findings suggest that serum PFAS concentrations were associated with moderately increased systolic and diastolic blood pressure in a large highly exposed young adult population. Although the magnitude of the observed effect was relatively small, if confirmed it would be of clinical significance since even small increases in blood pressure levels at population level may be associated to a raised risk of adverse outcomes such as cardiovascular disease and target organ damage.

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Transcriptional changes in steroidogenesis by perfluoroalkyl acids (PFOA and PFOS) regulate the synthesis of sex hormones in H295R cells

Cited by 81 publications

References 44 publications

Perfluoroalkyl substances are associated with elevated blood pressure and hypertension in highly exposed young adults

Perfluoroalkyl substances are associated with elevated blood pressure and hypertension in highly exposed young adults

Effects of long-term endocrine disrupting compound exposure on Macaca mulatta embryonic stem cells

Perfluoroalkyl Substances Are Associated With Elevated Blood Pressure and Hypertension in Highly Exposed Young Adults

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