Per- and polyfluoroalkyl substances (PFASs) such as perfluorooctanoic acid (PFOA) and perfluorooctanesulfonic acid (PFOS) are persistent in the environment and bioaccumulate in wildlife and humans, ...potentially causing adverse health effects at all stages of life. Studies from human pregnancy have shown that exposure to these contaminants are associated with placental dysfunction and fetal growth restriction; however, studies in humans are confounded by genetic and environmental factors. Here, we synthesize the available results from mouse models of pregnancy to show the causal effects of prenatal exposure to PFOA and PFOS on placental and fetal development and on neurocognitive function and metabolic disorders in offspring. We also propose gaps in the present knowledge and provide suggestions for future research studies. Summary Sentence Using mouse models of pregnancy, maternal exposure to perfluoroalkyl substances has been shown to have significant impact on placental development, fetal growth, neurocognitive function, and risk for disease in both mother and offspring.
Fluorotelomer ethoxylates are reported in indoor dust and industrial wastewater.
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Concerns regarding the persistence, bioaccumulation behaviour, and toxicity of perfluorooctanoic acid ...and perfluorooctane sulfonic acid have resulted in the creation of thousands of replacement perfluoroalkyl substances (PFAS). This study reports on the discovery of fluorotelomer ethoxylates (FTEO) in indoor dust (9/15 samples), and industrial effluents (14/37 samples) using gas chromatographic cyclic ion mobility mass spectrometry (GC-cIMS). By filtering the detected unknowns by mass and collision-cross section, a series of FTEO homologues were revealed with the formula F-(CF2)n(C2H4O)xH, where n = 6,8,10, and x = 4–12. The highest concentrations were observed in samples collected from healthcare facilities, consistent with the potential use of these compounds in anti-fog products, sprays used to prevent condensation on eyeglasses. FTEOs were also detected in c. 40 % of industrial effluent samples, with the highest concentrations in electroplating facilities, manufacturers of cosmetics and personal care products, and linen cleaning services for healthcare and work uniforms. These results suggest that FTEOs may well be widespread pollutants that are more persistent than previously thought, underlining the need for further study of their occurrence and potential impact to human health and the environment.
Poly- and perfluoroalkyl substances (PFAS) are a group of compounds with uses in industry and many consumer products. Concerns about the potential health effects of these compounds resulted in ...regulation by the Stockholm Convention on the use of three of the most common PFAS, including perfluorooctanoic acid (PFOA). Thousands of PFAS remain in production that are unregulated and for which their toxicity is unknown. Our group recently identified a new class of PFAS, fluorotelomer ethoxylates (FTEOs), in indoor dust and industrial wastewater. In this study, we investigated the effect of PFAS on placental metabolism by exposing healthy, pregnant CD-1 mice to PFOA or FTEOs at one of three concentrations (0 ng/L (controls), 5 ng/L, 100 ng/L) (n = 7–8/group). While PFOA is banned and PFOA concentrations in human blood are decreasing, we hypothesize that FTEOs will cause adverse pregnancy outcomes similar to PFOA, the compounds they were meant to replace. Placental tissue samples were collected at embryonic day 17.5 and 1H solid-state magic angle spinning nuclear magnetic resonance spectroscopy was used to determine the relative concentration of placental metabolites (n = 18–20/group). At the highest concentration, the relative concentrations of glucose and threonine were increased and the relative concentration of creatine was decreased in the PFOA-exposed placentas compared to controls (p < 0.05). In contrast, the relative concentrations of asparagine and lysine were decreased and the relative concentration of creatine was increased in the FTEOs-exposed placentas compared to controls (p < 0.05). Partial least squares - discriminant analysis showed the FTEOs-exposed and control groups were significantly separated (p < 0.005) and pathway analysis found four biochemical pathways were perturbed following PFOA exposure, while one pathway was altered following FTEOs exposure. Maternal exposure to PFOA and FTEOs had a significant impact on the placental metabolome, with the effect depending on the pollutant. This work motivates further studies to determine exposure levels and evaluate associations with adverse outcomes in human pregnancies.
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•Fluorotelomer ethoxylates (FTEOs) were previously found to be environmentally persistent.•The health impacts of FTEOs are unknown.•Exposure of pregnant mice to FTEOs results in abnormal placental metabolism.
While microplastics have been recently detected in human blood and the placenta, their impact on human health is not well understood. Using a mouse model of environmental exposure during pregnancy, ...our group has previously reported that exposure to polystyrene micro- and nanoplastics throughout gestation results in fetal growth restriction. While polystyrene is environmentally relevant, polyethylene is the most widely produced plastic and amongst the most commonly detected microplastic in drinking water and human blood. In this study, we investigated the effect of maternal exposure to polyethylene micro- and nanoplastics on fetal growth and placental function. Healthy, pregnant CD-1 dams were divided into three groups: 10
ng/L of 740-4990 nm polyethylene with surfactant in drinking water (n = 12), surfactant alone in drinking water (n = 12) or regular filtered drinking water (n = 11). At embryonic day 17.5, high-frequency ultrasound was used to investigate the placental and fetal hemodynamic responses following exposure. While maternal exposure to polyethylene did not impact fetal growth, there was a significant effect on placental function with a 43% increase in umbilical artery blood flow in the polyethylene group compared to controls (p < 0.01). These results suggest polyethylene has the potential to cause adverse pregnancy outcomes through abnormal placental function.
Placental metabolism determines the amount of nutrients available to the fetus and may be altered in pregnancies complicated by fetal growth restriction (FGR). To study which metabolites are ...associated with FGR, we performed 1H high-resolution magic angle spinning magnetic resonance spectroscopy of placental tissue from endothelial nitric oxide synthase knockout (eNOS KO) mice, a model of FGR, and C57BL/6J controls at embryonic day 17.5 (n = 24/genotype). The relative concentration of glucose was increased in the placentas of eNOS KO mice compared to controls (p = 0.006). This study highlights the potential for glucose as a biomarker of abnormal placental metabolism that leads to FGR.
•1H HRMAS MRS is a promising method to study placental metabolism.•Glucose concentration was elevated in the placentas of growth-restricted murine fetuses.•Glucose has potential to be a biomarker of abnormal placental metabolism.
Maternal exposure to microplastics and nanoplastics has been shown to result in fetal growth restriction in mice. In this study, we investigated the placental and fetal hemodynamic responses to ...plastics exposure in mice using high-frequency ultrasound. Healthy, pregnant CD-1 dams were given either 106 ng/L of 5 µm polystyrene microplastics or 106 ng/L of 50 nm polystyrene nanoplastics in drinking water throughout gestation and were compared with controls. Maternal exposure to both microplastics and nanoplastics resulted in evidence of placental dysfunction that was highly dependent on the particle size. The umbilical artery blood flow increased by 48% in the microplastic-exposed group and decreased by 25% in the nanoplastic-exposed group compared to controls (p < 0.05). The microplastic- and nanoplastic-exposed fetuses showed a significant decrease in the middle cerebral artery pulsatility index of 10% and 13%, respectively, compared to controls (p < 0.05), indicating vasodilation of the cerebral circulation, a fetal adaptation that is part of the brain sparing response to preserve oxygen delivery. Hemodynamic markers of placental dysfunction and fetal hypoxia were more pronounced in the group exposed to polystyrene nanoplastics, suggesting nanoplastic exposure during human pregnancy has the potential to disrupt fetal brain development, which in turn may cause suboptimal neurodevelopmental outcomes. Summary Sentence Exposure to polystyrene micro- and nanoplastics during pregnancy causes placental dysfunction, leading to fetal blood flow redistribution and growth restriction in mice. Graphical Abstract
Introduction
Plastics used in everyday materials accumulate as waste in the environment and degrade over time. The impacts of the resulting particulate micro- and nanoplastics on human health remain ...largely unknown. In pregnant mice, we recently demonstrated that exposure to nanoplastics throughout gestation and during lactation resulted in changes in brain structure detected on MRI. One possible explanation for this abnormal postnatal brain development is altered fetal brain metabolism.
Objectives
To determine the effect of maternal exposure to nanoplastics on fetal brain metabolism.
Methods
Healthy pregnant CD-1 mice were exposed to 50 nm polystyrene nanoplastics at a concentration of 10
6
ng/L through drinking water during gestation. Fetal brain samples were collected at embryonic day 17.5 (
n
= 18–21 per group per sex) and snap-frozen in liquid nitrogen. Magic angle spinning nuclear magnetic resonance was used to determine metabolite profiles and their relative concentrations in the fetal brain.
Results
The relative concentrations of gamma-aminobutyric acid (GABA), creatine and glucose were found to decrease by 40%, 21% and 30% respectively following maternal nanoplastic exposure when compared to the controls (p < 0.05). The change in relative concentration of asparagine with nanoplastic exposure was dependent on fetal sex (p < 0.005).
Conclusion
Maternal exposure to polystyrene nanoplastics caused abnormal fetal brain metabolism in mice. The present study demonstrates the potential impacts of nanoplastic exposure during fetal development and motivates further studies to evaluate the risk to human pregnancies.
Poly- and perfluoroalkyl substances are a ubiquitous class of compounds which are considered persistent organic pollutants. Many of these compounds are unregulated and understudied but are still ...widely used. One group of these compounds are fluorotelomer ethoxylates, which recently emerged as compounds of interest following their detection in the environment. To determine the health impacts of these persistent compounds, healthy pregnant CD-1 mice were exposed to 0 ng L
−1
(
n
= 8), 5 ng L
−1
(
n
= 8), or 100 ng L
−1
(
n
= 7) fluorotelomer ethoxylates in drinking water throughout gestation. At gestational day 17.5 (term is 18.5 days), high-frequency ultrasound was performed to investigate the placental and fetal hemodynamic responses following exposure. Maternal exposure to fluorotelomer ethoxylates showed evidence of placental insufficiency, with a significant increase in placental weights (
p
< 0.05), a decrease in the umbilical artery blood flow (
p
< 0.01) and vasodilation of the cerebral circulation (
p
< 0.01), consistent with brain sparing to preserve oxygen delivery to the brain. These results demonstrate that fluorotelomer ethoxylates cause developmental toxicity and motivate further work to evaluate the risk to human pregnancies and other vulnerable populations.
Maternal exposure to environmentally relevant concentrations of fluorotelomer ethoxylates, an unregulated group of poly- and perfluoroalkyl substances, results in placental insufficiency and fetal distress in mice.
Introduction
During pregnancy, appropriate placental metabolism is essential for fetuses to reach their growth potential. However, metabolic mechanisms during pregnancy remain poorly understood. ...Determination of the levels of placental metabolites in healthy pregnancy and how they change throughout gestation is critical for understanding placental function.
Objective
To determine the effects of gestational age on placental metabolites using healthy pregnant mice.
Methods
In the present study, we collected placental tissue samples from healthy pregnant mice at three timepoints in late gestation (
n
= 16 placentas per gestational age). Metabolite profiles were determined using
1
H high-resolution magic angle spinning magnetic resonance spectroscopy (HRMAS MRS).
Results
Using HRMAS MRS, we identified 14 metabolites in murine placental tissue samples. The relative concentration of 12 of the 14 metabolites remains unchanged throughout late gestation. Lysine was found to decrease significantly (p = 0.04) and glucose showed an inverted U-shape relationship (p = 0.03) with gestational age.
Conclusion
This study demonstrated the feasibility of HRMAS MRS to determine relative metabolite concentrations in murine placental tissue. These findings establish baseline levels of placental tissue metabolite profiles and will serve as reference ranges for future studies using mouse models of fetal distress.
The presence of microplastics and nanoplastics (NPs) has recently been reported in human blood and tissues, raising concerns about their potential impacts on human health and fetal development. In ...this study, we investigated the effects of maternal exposure to NPs on the timing of developmental milestones and on brain structure using experimental mice. Healthy, pregnant CD-1 dams were given 10
6
ng L
−1
of 50 nm polystyrene NPs in drinking water throughout gestation and lactation and the postnatal behavior and neuroanatomy of the offspring were studied. We found that NPs exposure resulted in earlier time to eye opening in male offspring but not in females (
p
= 0.01). 3D high-resolution
ex vivo
magnetic resonance imaging (MRI) revealed that offspring exposed to NPs had focal differences compared to controls in multiple brain structures that are involved in motor function, learning and memory, and physiological functions including the motor cortex, hippocampus, hypothalamus, medulla, and olfactory bulb. Several of these MRI-detectable neuroanatomical changes were dependent on sex. Our study demonstrates that maternal exposure to NPs results in abnormal postnatal brain development in the mouse. Further investigations are needed to determine the mechanisms whereby NPs exposure during fetal development may adversely affect dimensions of brain function in a sex-dependent manner.
Maternal exposure to polystyrene nanoplastics impact postnatal brain development in mouse offspring. This work motivates further studies to determine the levels of nanoplastics in the environment.
