Activation of Peroxisome Proliferator-Activated Receptor Gamma and Disruption of Progesterone Synthesis of 2-Ethylhexyl Diphenyl Phosphate in Human Placental Choriocarcinoma Cells: Comparison with Triphenyl Phosphate

Hu, Wenxin; Gao, Fumei; Zhang, Hong; Hiromori, Youhei; Arakawa, Shuhei; Nagase, Hisamitsu; Nakanishi, Takashi; Hu, Jianying

doi:10.1021/acs.est.7b00872

Cited by 92 publications

(47 citation statements)

References 34 publications

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“…One study in mice demonstrated that in utero exposure to triphenyl phosphate (TPhP), the parent compound of DPhP, alters fetal and maternal liver insulin growth factor signaling, which is critical to the control of fetal growth and development [ 57 , 58 ]. Additional research using a human placental cell line has also established that TPhP exposure increases both progesterone and human chorionic gonadotropin secretion via activation of the peroxisome proliferator-activated receptor gamma [ 59 ]. Changes to placental hormone production has important implications for both placental and fetal growth and development [ 58 ].…”

Section: Discussionmentioning

confidence: 99%

Prenatal exposure to consumer product chemical mixtures and size for gestational age at delivery

et al. 2021

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Background While fetal growth is a tightly regulated process, it is sensitive to environmental exposures that occur during pregnancy. Many commonly used consumer products contain chemicals that can disturb processes underlying fetal growth. However, mixtures of these chemicals have been minimally examined. We investigated associations between prenatal exposure to 33 consumer product chemicals (nine organophosphate ester flame retardant [OPE] metabolites, 12 phthalate metabolites, and 12 phenols) and the odds of small- or large-for-gestational age (SGA and LGA) births. Methods This case-control study was comprised of SGA (N = 31), LGA (N = 28), and appropriate for gestational age control (N = 31) births selected from the larger LIFECODES cohort. Biomarkers of exposure to consumer product chemicals were quantified in maternal urine collected from up to three study visits during pregnancy. In a single-pollutant approach, odds ratios (OR) and 95% confidence intervals (CI) of SGA and LGA associated with an interquartile range (IQR)-increase in exposure biomarkers were estimated using multinomial logistic regression. In a multi-pollutant approach, quantile g-computation was used to jointly estimate the OR (95% CI) of SGA and LGA per simultaneous one quartile-change in all biomarkers belonging to each chemical class. Results Among the 33 biomarkers analyzed, 20 were detected in at least 50% of the participants. After adjusting for potential confounders, we observed reduced odds of LGA in association with higher urinary concentrations of several exposure biomarkers. For example, an IQR-increase in the OPE metabolite, diphenyl phosphate, was associated with lower odds of LGA (OR: 0.40 [95% CI: 0.18, 0.87]). Using quantile g-computation, we estimated lower odds of an LGA birth for higher OPE metabolite concentrations (OR: 0.49 [95% CI: 0.27, 0.89]) and phthalate metabolite concentrations (OR: 0.23 [95% CI: 0.07, 0.73]). Associations between consumer product chemicals and SGA were largely null. Conclusions Joint exposure to OPEs and phthalates was associated with lower odds of delivering LGA. Associations with LGA could indicate a specific impact of these exposures on the high end of the birth weight spectrum. Future work to understand this nuance in the associations between consumer product chemical mixtures and fetal growth is warranted.

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Section: Discussionmentioning

confidence: 99%

Prenatal exposure to consumer product chemical mixtures and size for gestational age at delivery

et al. 2021

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“…Several biological mechanisms by which OPEs could alter metabolism have been proposed. Emerging laboratory and human evidence indicates that OPEs may interfere with sex steroid and thyroid hormones ( Farhat et al 2013 ; Kim et al 2015 ; Krivoshiev et al 2016 ; Liu et al 2012b ; Meeker and Stapleton 2010 ; Preston et al 2017 ; Schang et al 2016 ; Wang et al 2015 ; Zhang et al, 2016a ), peroxisome proliferator-activated receptors (PPARs) ( Belcher et al 2014 ; Fang et al 2015 ; Hu et al 2017 ; Kojima et al 2013 ; Pillai et al 2014 ), and induce oxidative stress ( Arukwe et al 2016 ; Chen et al 2015 ; Jin et al 2016 ; Lu et al 2017 ; Yan et al 2017 ). These biologic pathways serve well-known roles in adipose tissue development and obesity risk.…”

Section: Introductionmentioning

confidence: 99%

Associations between urinary organophosphate ester metabolites and measures of adiposity among U.S. children and adults: NHANES 2013–2014

Boyle

Buckley

Quirós-Alcalá

2019

Environment International

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Background: Organophosphate esters (OPEs) are synthetic chemicals found in many consumer products, including furniture, electronics, processed foods, and building materials. Emerging in vitro and in vivo studies suggest that OPEs are metabolism disrupting compounds; however, epidemiologic studies investigating their associations with adiposity markers are sparse. Objective: We examined cross-sectional associations between OPE biomarkers and adiposity measures among U.S. children and adults participating in the National Health and Nutrition Examination Survey (NHANES: 2013–2014). Methods: Concentrations of five OPE metabolites were quantified in urine: diphenyl phosphate (DPHP), bis(1,3-dichloro-2-propyl) phosphate (BDCPP), bis(2-chloroethyl) phosphate (BCEP), dibutyl phosphate (DBUP), and bis (1-chloro-2-propyl) phosphate (BCPP). We conducted covariate-adjusted logistic and linear regressions to examine associations between log 2 -transformed and dichotomized OPE metabolite concentrations and obesity, body mass index (BMI), and waist circumference (WC), separately among 784 children (6–19 years) and 1672 adults (≥20 years). We also assessed heterogeneity of associations by sex. Results: DBUP concentrations were inversely associated with the prevalence odds of being obese vs. normal weight in children (adjusted Prevalence Odds Ratio, aPOR: 0.82, 95% Confidence Interval, 95% CI: 0.70, 0.95) and adults (aPOR: 0.83, 95% CI: 0.72, 0.96). DBUP was also significantly associated with lower BMI z-scores (β:−0.08, 95% CI:−0.17, 0.01) and WC (β:−0.71, 95% CI: −1.49, 0.07) in children. BCEP concentrations were associated with increased prevalence odds of being overweight vs. normal weight (aPOR: 1.15, 95% CI: 1.01, 1.32) among children; similar, albeit not statistically significant, relationships were observed with other child adiposity outcomes. Among adults, detectable BCPP concentrations were associated with increased prevalence odds of being obese vs. normal weight (aPOR: 1.70, 95% CI: 1.21, 2.38) and having a high vs. normal WC (aPOR:1.51, 95% CI: 1.11, 2.07) as well as higher BMI (β: 1.31, 95% CI: 0.30, 2.33). Other OPE metabolites were not consistently associated with adiposity measures among adults. Although associations of BCPP exposure with adiposity outcomes were generally inverse among boys, but not girls, we did not observe consistent evidence of sexually-dimorphic associations for other OPE metabolites. Conclusions: Exposure to select OPEs may be differentially associated with body size among children and adults. Given the cross-sectional design of the present study, future prospective studies are needed to confirm these findings.

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“…One study in mice demonstrated that in utero exposure to triphenyl phosphate (TPhP), the parent compound of DPhP, alters fetal and maternal liver insulin growth factor signaling, which is critical to the control of fetal growth and development (57,58). Additional research using a human placental cell line has also established that TPhP exposure increases both progesterone and human chorionic gonadotropin secretion via activation of the peroxisome proliferator-activated g p p p receptor gamma (59). Changes to placental hormone production has important implications for both placental and fetal growth and development (58).…”

Section: Discussionmentioning

confidence: 99%

Prenatal exposure to consumer product chemical mixtures and size for gestational age at delivery

Bommarito

Welch

Keil

et al. 2021

Preprint

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Background: While fetal growth is a tightly regulated process, it is sensitive to environmental exposures that occur during pregnancy. Many commonly used consumer products contain chemicals that can disturb processes underlying fetal growth. However, mixtures of these chemicals have been minimally examined. We investigated associations between prenatal exposure to 33 consumer product chemicals (nine organophosphate ester flame retardant [OPE] metabolites, 12 phthalate metabolites, and 12 phenols) and the odds of small- or large-for-gestational age (SGA and LGA) births.Methods: This case-control study was comprised of SGA (N = 31), LGA (N = 28), and appropriate for gestational age control (N = 31) births selected from the larger LIFECODES cohort. Biomarkers of exposure to consumer product chemicals were quantified in maternal urine collected from up to three study visits during pregnancy. In a single-pollutant approach, odds ratios (OR) and 95% confidence intervals (CI) of SGA and LGA associated with an interquartile range (IQR)-increase in exposure biomarkers were estimated using multinomial logistic regression. In a multi-pollutant approach, quantile g-computation was used to jointly estimate the OR (95% CI) of SGA and LGA per simultaneous one quartile-change in all biomarkers belonging to each chemical class. Results: Among the 33 biomarkers analyzed, 20 were detected in at least 50% of the participants. After adjusting for potential confounders, we observed reduced odds of LGA in association with higher urinary concentrations of several exposure biomarkers. For example, an IQR-increase in the OPE metabolite, diphenyl phosphate, was associated with lower odds of LGA births (OR: 0.40 [95% CI: 0.18, 0.87]). Using quantile g-computation, we estimated lower odds of an LGA birth for higher OPE metabolite concentrations (OR: 0.49 [95% CI: 0.27, 0.89]) and phthalate metabolite concentrations (OR: 0.23 [95% CI: 0.07, 0.73]). Associations between consumer product chemicals and SGA were largely null. Conclusions: Joint exposure to OPEs and phthalates was associated with lower odds of delivering LGA. Associations with LGA could indicate a specific impact of these exposures on the high end of the birth weight spectrum. Future work to understand this nuance in the associations between consumer product chemical mixtures and fetal growth is warranted.

show abstract

Activation of Peroxisome Proliferator-Activated Receptor Gamma and Disruption of Progesterone Synthesis of 2-Ethylhexyl Diphenyl Phosphate in Human Placental Choriocarcinoma Cells: Comparison with Triphenyl Phosphate

Cited by 92 publications

References 34 publications

Prenatal exposure to consumer product chemical mixtures and size for gestational age at delivery

Prenatal exposure to consumer product chemical mixtures and size for gestational age at delivery

Associations between urinary organophosphate ester metabolites and measures of adiposity among U.S. children and adults: NHANES 2013–2014

Prenatal exposure to consumer product chemical mixtures and size for gestational age at delivery

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