Effects of <i>In Utero</i> Exposure to Perfluorooctane Sulfonate on Placental Functions

Wan, Hin Ting; Wong, Aman Yi-Man; Shi, Feng; Wong, Chris K C

doi:10.1021/acs.est.0c06569

Cited by 22 publications

(19 citation statements)

References 60 publications

(87 reference statements)

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“…Placental weight and placenta/fetus weight ratios were increased in treated groups, suggesting compensatory placental growth. Placentas from pregnant mice dosed with PFOS at dosages that caused FGR exhibited a reduction in maternal–fetal transport of glucose and amino acids and increased concentrations of corticosterone (Wan et al, 2020).…”

Section: Resultsmentioning

confidence: 99%

A putative adverse outcome network for neonatal mortality and lower birth weight in rodents: Applicability to per‐ and polyfluoroalkyl substances and relevance to human health

Rogers

Heintz

Thompson

et al. 2023

Birth Defects Research

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Background Some per‐ and poly‐fluoroalkyl substances (PFAS) cause neonatal mortality and lower birth weight in rodents. We constructed an Adverse Outcome Pathway (AOP) network for neonatal mortality and lower birth weight in rodents, comprising three putative AOPs. We then assessed strengths of the evidence for the AOPs and applicability to PFAS. Finally, we considered the relevance of this AOP network to human health. Methods Literature searches targeted PFAS, peroxisome proliferator‐activated receptor (PPAR) agonists, other nuclear receptors, relevant tissues, and developmental targets. We used reviews of established biology and described results of studies with prenatal PFAS exposure that assessed birth weight and neonatal survival. Molecular initiating events (MIEs) and key events (KEs) were proposed and strengths of KE relationships (KERs), applicability to PFAS, and human relevance were assessed. Results Neonatal mortality has been observed in rodents following gestational exposure to most longer chain PFAS studied, often coincident with lower birth weight. In AOP 1, PPARα activation and PPARγ activation or downregulation are MIEs; placental insufficiency, fetal nutrient restriction, neonatal hepatic glycogen deficit, and hypoglycemia are KEs leading to neonatal mortality and lower birth weight. In AOP 2, constitutive androstane receptor (CAR) and pregnane X receptor (PXR) activation upregulates Phase II metabolism, lowering maternal circulating thyroid hormones. In AOP 3, disrupted pulmonary surfactant function and PPARγ downregulation cause neonatal airway collapse and mortality from respiratory failure. Conclusions It is likely that different components of this AOP network will apply to different PFAS, largely determined by which nuclear receptors they activate. The MIEs and KEs in this AOP network can occur in humans, but differences in PPAR structure and function, and the timeline of liver and lung development, suggest that humans may be less susceptible to this AOP network. This putative AOP network elucidates knowledge gaps and research needed to better understand the developmental toxicity of PFAS.

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Section: Resultsmentioning

confidence: 99%

A putative adverse outcome network for neonatal mortality and lower birth weight in rodents: Applicability to per‐ and polyfluoroalkyl substances and relevance to human health

Rogers

Heintz

Thompson

et al. 2023

Birth Defects Research

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“…To the best of our knowledge, this is the first report in humans though this phenomenon has been previously observed in animals. 26,27 Li et al found that 20 mg/kg PFOS exposure during pregnancy significantly reduced the BW of Sprague Dawley rat by increasing fetal serum corticosterone levels. 26 Wan et al also reported that pregnant mice exposed to 3 mg/kg PFOS from gestational day 4.5−17.5 reduced the fetal body weight and increased the cortisol levels in the placenta and liver.…”

Section: Influence Of Glucocorticoid On the Association Between Pfas ...mentioning

confidence: 99%

“…26 Wan et al also reported that pregnant mice exposed to 3 mg/kg PFOS from gestational day 4.5−17.5 reduced the fetal body weight and increased the cortisol levels in the placenta and liver. 27 While the underlying mechanism is unknown, more epidemiological and toxicology studies are needed to determine the adverse association between PFAS exposure and fetal growth and the potential mediating role of fetal glucocorticoid.…”

Section: Influence Of Glucocorticoid On the Association Between Pfas ...mentioning

confidence: 99%

“…Glucocorticoids, produced by adrenal glands, are thought to play a key role in regulating fetal growth. , Excessive glucocorticoid exposure during pregnancy could lead to a long-term “programming” of fetal hypothalamus-pituitary–adrenal gland (HPA) axis function and affect fetal behavior and organ maturation. − Previous studies have demonstrated that prenatal PFAS exposure could stimulate the secretion of glucocorticoid directly or disturb the glucocorticoid regulation in the placenta, , leading to glucocorticoid overexposure of fetus during the pregnancy. This, in turn, activates the fetal HPA axis and affect the hormone level and placental function, resulting in adverse outcomes. − However, to the best of our knowledge, there are no epidemiological study reporting the effect of glucocorticoid on the relationship between prenatal PFAS exposure and fetal growth. Only three human studies have demonstrated that PFAS exposure was associated with glucocorticoid levels, while the relevance was not consistent. − For example, Goudarzi et al found negative association between maternal PFOS and cord cortisol (active glucocorticoid in humans) in a birth cohort study (The Hokkaido Study), while Dreyer et al reported positive associations in pregnant women.…”

Section: Introductionmentioning

confidence: 99%

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Fetal Glucocorticoid Mediates the Association between Prenatal Per- and Polyfluoroalkyl Substance Exposure and Neonatal Growth Index: Evidence from a Birth Cohort Study

Cai

Mohammed

et al. 2023

Environ. Sci. Technol.

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Glucocorticoid plays a key role in the growth and organ maturation of fetus. However, the effect of glucocorticoid on the association between per-and polyfluoroalkyl substance (PFAS) exposure and fetal growth is still unknown. We detected cord cortisol (active glucocorticoid in human) and 34 PFAS concentrations in the maternal serum samples, which were collected from 202 mother-fetus pairs in the Maoming Birth Cohort from 2015 to 2018. The mediation effect of cord cortisol on the association between maternal PFAS and the neonatal growth index (NGI) was estimated. We found that higher PFAS concentrations were associated with lower NGI in terms of ponderal index, birth weight (BW), head circumference (HC), and its z-scores (BWZ and HCZ) (P < 0.05). Fetal cortisol could mediate 12.6−27.3% of the associations between PFAS and NGI. Specifically, cord cortisol mediated the association between branched perfluorooctane sulfonate (branched PFOS) and HCZ by 20.4% and between perfluorooctanoate (PFOA) and HCZ by 27.3%. Our findings provide the first epidemiological data evincing that fetal cortisol could mediate the association between prenatal PFAS exposure and fetal growth. Further investigations are recommended to elucidate the interactions among cord cortisol, PFAS, and fetal growth.

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“…The placenta is the interface between mother and fetus and is a critical organ modulating fetal development, metabolism, immunity, hormone regulation, and parturition initiation. − The transfer of xenobiotics from mother to fetus rarely avoids placental transport, and the placenta is therefore a potential target for fetal exposure to PFASs before birth . Indirect effects via the placenta may account for adverse birth outcomes induced by PFAS prenatal exposure. − Despite widespread detection of PFASs in the placenta − and toxicological studies reporting PFAS-induced placental injury and dysfunction, ,, no population-based studies on the effects of PFASs on the placenta or the influence of underlying placental injuries on the fetus have been conducted. In addition, for existing studies, the detected placentas were not explicitly analyzed on spatial separation, and the influence of the distinctive structural and functional features of the subchorionic plate (fetal side) and parabasal plate (maternal side) on placental PFAS distribution has been largely ignored. , Accordingly, there is a critical need to investigate region-specific PFAS distribution in the placenta and the corresponding in situ health effects to help elucidate intraplacental distribution and prenatal/perinatal health risks.…”

Section: Introductionmentioning

confidence: 99%

Unveiling Distribution of Per- and Polyfluoroalkyl Substances in Matched Placenta-Serum Tetrads: Novel Implications for Birth Outcome Mediated by Placental Vascular Disruption

Pan

Qiu

et al. 2023

Environ. Sci. Technol.

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The placenta is pivotal for fetal development and maternal–fetal transfer of many substances, including per- and polyfluoroalkyl substances (PFASs). However, the intraplacental distribution of PFASs and their effects on placental vascular function remain unclear. In this study, 302 tetrads of matched subchorionic placenta (fetal-side), parabasal placenta (maternal-side), cord serum, and maternal serum samples were collected from Guangzhou, China. Eighteen emerging and legacy PFASs and five placental vascular biomarkers were measured. Results showed that higher levels of perfluorooctanoic (PFOA), perfluorooctane sulfonic acid (PFOS), and chlorinated polyfluorinated ether sulfonic acids (Cl-PFESAs) were detected in subchorionic placenta compared to parabasal placenta. There were significant associations of PFASs in the subchorionic placenta, but not in the serum, with placental vascular biomarkers (up to 32.5%) and lower birth size. Birth weight was negatively associated with PFOA (β: −103.8, 95% CI: −186.3 and −21.32) and 6:2 Cl-PFESA (β: −80.04, 95% CI: −139.5 and −20.61), primarily in subchorionic placenta. Mediation effects of altered placental angiopoietin-2 and vascular endothelial growth factor receptor-2 were evidenced on associations of adverse birth outcomes with intraplacental PFOS and 8:2 Cl-PFESA, explaining 9.5%–32.5% of the total effect. To the best of our knowledge, this study is the first to report on differential intraplacental distribution of PFASs and placental vascular effects mediating adverse birth outcomes and provides novel insights into the placental plate-specific measurement in PFAS-associated health risk assessment.

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Effects of In Utero Exposure to Perfluorooctane Sulfonate on Placental Functions

Cited by 22 publications

References 60 publications

A putative adverse outcome network for neonatal mortality and lower birth weight in rodents: Applicability to per‐ and polyfluoroalkyl substances and relevance to human health

A putative adverse outcome network for neonatal mortality and lower birth weight in rodents: Applicability to per‐ and polyfluoroalkyl substances and relevance to human health

Fetal Glucocorticoid Mediates the Association between Prenatal Per- and Polyfluoroalkyl Substance Exposure and Neonatal Growth Index: Evidence from a Birth Cohort Study

Unveiling Distribution of Per- and Polyfluoroalkyl Substances in Matched Placenta-Serum Tetrads: Novel Implications for Birth Outcome Mediated by Placental Vascular Disruption

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