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.
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.
INTRODUCTIONOur understanding of the etiology of preterm birth (PTB) is incomplete; however, recent evidence has found a strong association between placental dysfunction and PTB. Altered placental ...metabolism may precede placental dysfunction and therefore the study of placental metabolic profiles could identify early biomarkers of PTB. In this study, we evaluated the placental metabolome in PTB in intact tissue samples using nuclear magnetic resonance (NMR) and spectral editing.METHODSPlacental tissue samples were collected from nine term pregnancies and nine preterm pregnancies (<37 weeks' gestation). 1H NMR experiments on unprocessed tissue samples were performed using a high field magnet (500 MHz spectrometer) and a comprehensive multiphase NMR probe. The relative concentrations of 23 metabolites were corrected for gestational age and compared between groups.RESULTSThe relative concentration of valine, glutamate and creatine were significantly decreased while alanine, choline and glucose were elevated in placentas from PTB pregnancies compared to controls (p < 0.05). Multivariate analysis using principal component analysis showed the PTB and control groups were significantly separated (p < 0.0001) and pathway analysis identified perturbations in the glycine, serine and threonine metabolism, aminoacyl-tRNA biosynthesis and valine, leucine and isoleucine biosynthesis pathways.CONCLUSIONPTB is associated with significant alterations in placental metabolism. This study helps improve our understanding of the etiology of PTB. It also highlights the potential for small molecule metabolites to serve as placental metabolic biomarkers to aid in the prediction and diagnosis of PTB. The results can be translated to clinical use via in utero magnetic resonance spectroscopy.
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
The rapid growth in the worldwide use of plastics has resulted in a vast accumulation of microplastics in the air, soil and water. The impact of these microplastics on pregnancy and ...fetal development remains largely unknown. In pregnant mice, we recently demonstrated that exposure to micro- and nanoplastics throughout gestation resulted in significant fetal growth restriction. One possible explanation for reduced fetal growth is abnormal placental metabolism.
Objectives
To evaluate the effect of maternal exposure to microplastics on placental metabolism.
Methods
In the present study, CD-1 pregnant mice were exposed to 5 μm polystyrene microplastics in filtered drinking water at one of four concentrations (0 ng/L (controls), 10
2
ng/L, 10
4
ng/L, 10
6
ng/L) throughout gestation (
n
= 7–11/group). At embryonic day 17.5, placental tissue samples were collected (
n
= 28–44/group). Metabolite profiles were determined using
1
H high-resolution magic angle spinning magnetic resonance spectroscopy.
Results
The relative concentration of lysine (p = 0.003) and glucose (p < 0.0001) in the placenta were found to decrease with increasing microplastic concentrations, with a significant reduction at the highest exposure concentration. Multivariate analysis identified shifts in the metabolic profile with MP exposure and pathway analysis identified perturbations in the biotin metabolism, lysine degradation, and glycolysis/gluconeogenesis pathways.
Conclusion
Maternal exposure to microplastics resulted in significant alterations in placental metabolism. This study highlights the potential impact of microplastic exposure on pregnancy outcomes and that efforts should be made to minimize exposure to plastics, particularly during pregnancy.
Introduction
Endothelial nitric oxide synthase (eNOS) produces nitric oxide, which is essential for a variety of physiological functions in the brain. Previous work has demonstrated the detrimental ...effects of eNOS deficiency on brain function in male eNOS knockout (eNOS KO) mice. However, the effect of eNOS deficiency on brain structure and any association between these effects and sex is unknown.
Methods
This study used three‐dimensional high‐resolution ex vivo magnetic resonance imaging and behavioral tests of anxiety and cognitive performance to investigate structure–function relationships in the brain of female and male eNOS KO mice in young adulthood.
Results
While there were no differences in anxiety‐like behavior or locomotion, there was a sex‐specific deficit in contextual fear memory retention in male, but not in female, eNOS mice compared to wild‐type controls. Moreover, we found that eNOS deficiency induced changes in multiple brain regions that are involved in learning and fear memory including the hippocampus, amygdala, hypothalamus, and areas of the cortex. Several of these MRI‐detectable neuroanatomical changes were dependent on sex.
Conclusion
The observation that eNOS deficiency impacts brain structure at an early age demonstrates the importance of eNOS for healthy brain development.
Using behavioural tests of anxiety and cognitive function and high‐resolution ex vivo magnetic resonance imaging, we demonstrated the endothelial nitric oxide synthase deficiency in mice impacts brain structure and function in a sex dependent manner.
Objectives
To determine the relationship between blood flow in the fetal descending aorta and discordant umbilical arteries (UAs).
Methods
Pulsed wave Doppler of both UAs and the descending aorta was ...performed at 4‐weekly intervals between 14 and 40 weeks of gestation in 209 pregnant women. In datasets with discordant UAs, a linear mixed effects model was used to determine the categorical relationship between the UA pulsatility index (PI) (high, low and average) and the descending aorta PI.
Results
Of the 209 cases, 81 had a discordance of greater than 25% in UA PI during one of their visits. There were no differences in birth outcomes between the groups with concordant and discordant UA PIs. In the cases with discordant UA PIs, the descending aorta PI was most strongly associated with both the average UA PI (P = .008), and with the UA with the lower PI (P = .008).
Conclusions
The relationship between blood flow in the descending aorta and UAs is consistent with the law for combining resistances in parallel. Measurements of the descending aorta PI, particularly in a scenario with discordant UAs, may inform the stability of the feto‐placental circulation where discordant UA PIs are found.
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.
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.
