Paraoxonase 2 gene polymorphisms and prenatal phthalates' exposure in Chinese newborns

Xie, Chang-ming; Jin, Rong; Zhao, Yan; Lin, Ling; Li, Luxi; Chen, Jiao; Zhang, Yunhui

doi:10.1016/j.envres.2015.03.028

Cited by 17 publications

(11 citation statements)

References 44 publications

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“…Since fetuses are exposed to externally sourced chemicals from their mothers only and the meconium sample is the excreta of fetuses, the fact that the phthalates can be found in the meconium sample probably means that they can be transferred from mother to fetuses. Both our data and several other studies [ 36 , 37 , 38 ] found high rates of detection on the metabolites of frequently used phthalates, which highlighted the importance of biomonitoring of phthalates in meconium.…”

Section: Discussionsupporting

confidence: 84%

“…Another study of five meconium samples reported that only a few other DEHP metabolites were found in meconium [ 27 ]. MEHP has been measured in three Chinese studies that all reported very high median concentrations of approximately 3800 μg/g [ 40 ], 2900 μg/g [ 36 ], and 163.8 μg/g [ 38 ], compared to our study (median 65.2 ng/g). Median MnBP concentrations were 1700 μg/g and 101.70 μg/g, versus our study (28.1 ng/g).…”

Section: Discussioncontrasting

confidence: 56%

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Meconium Exposure to Phthalates, Sex and Thyroid Hormones, Birth Size and Pregnancy Outcomes in 251 Mother–Infant Pairs from Shanghai

Jialin

et al. 2020

IJERPH

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Phthalates are hormonally active pollutants. In-utero exposure to phthalates has been reported to be associated with birth size parameters and pregnancy outcomes. However, previous reports were inconsistent. We examined the associations between meconium exposure to phthalates and the effects on birth size parameters, pregnancy outcomes and sex and thyroid hormones in 251 mother–infant pairs from a Shanghai hospital. We measured 10 metabolites of phthalates in meconium samples collected during the first 24h after delivery. Information on seven birth size parameters (birth weight, birth length, abdominal circumference, head circumference, femur length, biparietal diameter and anogenital distance) and three pregnancy outcomes (gestational diabetes, premature rupture of membrane, and premature birth) was available from the birth record. Concentrations of free testosterone, estradiol (E2), thyroid stimulating hormone, concentrations of total and free thyroxine and triiodothyronine were measured from cord blood. Multivariate linear regression and logistic regression were used to estimate associations between phthalate exposure and health outcomes. mono-iso-butylphthalate (MiBP), mono-n-butylphthalate (MnBP) and mono-2-ethyl-5-oxohexyl phthalate (MEOHP) were positively associated with birth length and femur length which seemed more obvious in female newborn; MiBP, MnBP and mono-2-ethylhexylphthalate (MEHP) were positively associated with gestational diabetes mellitus (GDM) only in mothers with male newborns; monomethyl phthalate (MMP), MiBP and MEOHP were positively associated with E2 in male newborns. This study indicates that meconium exposure to phthalates may adversely affect some fetal growth parameters and GDM with a potential gender effect.

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Section: Discussionsupporting

confidence: 84%

Section: Discussioncontrasting

confidence: 56%

Meconium Exposure to Phthalates, Sex and Thyroid Hormones, Birth Size and Pregnancy Outcomes in 251 Mother–Infant Pairs from Shanghai

Jialin

et al. 2020

IJERPH

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“…The enzyme PON 1 is a nonspecific arylesterase/lactonase associated with xenobiotic detoxification and lipid metabolism 39 that has been implicated in modifying phthalate exposure on fetal development. 40 Indeed, maternal exposure to phthalates has also been associated with increased risk for childhood overweight/obesity. 41 As a result, we hypothesize that PON 1 expression and/or activity may be impaired in CF given the observations that both PA and MEHP are depleted in sweat specimens from CF affected infants ( Figure 3 ) while having a significant degree of correlation ( Figure 4 ) among sweat samples suggesting that they are likely metabolized via a common arylesterase/lactonase action.…”

Section: Discussionmentioning

confidence: 99%

The Sweat Metabolome of Screen-Positive Cystic Fibrosis Infants: Revealing Mechanisms beyond Impaired Chloride Transport

et al. 2017

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The sweat chloride test remains the gold standard for confirmatory diagnosis of cystic fibrosis (CF) in support of universal newborn screening programs. However, it provides ambiguous results for intermediate sweat chloride cases while not reflecting disease progression when classifying the complex CF disease spectrum given the pleiotropic effects of gene modifiers and environment. Herein we report the first characterization of the sweat metabolome from screen-positive CF infants and identify metabolites associated with disease status that complement sweat chloride testing. Pilocarpine-stimulated sweat specimens were collected independently from two CF clinics, including 50 unaffected infants (e.g., carriers) and 18 confirmed CF cases. Nontargeted metabolite profiling was performed using multisegment injection–capillary electrophoresis–mass spectrometry as a high throughput platform for analysis of polar/ionic metabolites in volume-restricted sweat samples. Amino acids, organic acids, amino acid derivatives, dipeptides, purine derivatives, and unknown exogenous compounds were identified in sweat when using high resolution tandem mass spectrometry, including metabolites associated with affected yet asymptomatic CF infants, such as asparagine and glutamine. Unexpectedly, a metabolite of pilocarpine, used to stimulate sweat secretion, pilocarpic acid, and a plasticizer metabolite from environmental exposure, mono(2-ethylhexyl)phthalic acid, were secreted in the sweat of CF infants at significantly lower concentrations relative to unaffected CF screen-positive controls. These results indicated a deficiency in human paraoxonase, an enzyme unrelated to mutations to the cystic fibrosis transmembrane conductance regulator (CFTR) and impaired chloride transport, which is a nonspecific arylesterase/lactonase known to mediate inflammation, bacterial biofilm formation, and recurrent lung infections in affected CF children later in life. This work sheds new light into the underlying mechanisms of CF pathophysiology as required for new advances in precision medicine of orphan diseases that benefit from early detection and intervention, including new molecular targets for therapeutic intervention.

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“…Surprisingly the two exogenous metabolites PA and MEHP, strongly correlated to pilocarpine-stimulated sweat secretion were found to be lower in CF infants with respect to unaffected screen-positive controls. PA is metabolized by the enzyme human paraoxonase 1 (PON 1) [68]; the enzyme family is also involved in modifying prenatale phtalate exposures [69]. These results suggested a correlation between the decreased levels of the two exogenous metabolites and a possible impaired activity of paraoxonase in CF individuals.…”

Section: Metabolomics For Biomarker Discovery: Support and Aid Cf Diamentioning

confidence: 97%

Proteomics and Metabolomics for Cystic Fibrosis Research

Liessi

Pedemonte

Armirotti

et al. 2020

IJMS

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The aim of this review article is to introduce the reader to the state-of-the-art of the contribution that proteomics and metabolomics sciences are currently providing for cystic fibrosis (CF) research: from the understanding of cystic fibrosis transmembrane conductance regulator (CFTR) biology to biomarker discovery for CF diagnosis. Our work particularly focuses on CFTR post-translational modifications and their role in cellular trafficking as well as on studies that allowed the identification of CFTR molecular interactors. We also show how metabolomics is currently helping biomarker discovery in CF. The most recent advances in these fields are covered by this review, as well as some considerations on possible future scenarios for new applications.

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Paraoxonase 2 gene polymorphisms and prenatal phthalates' exposure in Chinese newborns

Cited by 17 publications

References 44 publications

Meconium Exposure to Phthalates, Sex and Thyroid Hormones, Birth Size and Pregnancy Outcomes in 251 Mother–Infant Pairs from Shanghai

Meconium Exposure to Phthalates, Sex and Thyroid Hormones, Birth Size and Pregnancy Outcomes in 251 Mother–Infant Pairs from Shanghai

The Sweat Metabolome of Screen-Positive Cystic Fibrosis Infants: Revealing Mechanisms beyond Impaired Chloride Transport

Proteomics and Metabolomics for Cystic Fibrosis Research

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