Dataset Information

Early Gestational Exposure to Inhaled Ozone Impairs Maternal Uterine Artery and Cardiac Function.

ABSTRACT: Exposure to air pollutants such as ozone (O3) is associated with adverse pregnancy outcomes, including higher incidence of gestational hypertension, preeclampsia, and peripartum cardiomyopathy; however, the underlying mechanisms of this association remain unclear. We hypothesized that O3 exposures during early placental formation would lead to more adverse cardiovascular effects at term for exposed dams, as compared with late-term exposures. Pregnant Sprague Dawley rats were exposed (4 h) to either filtered air (FA) or O3 (0.3 or 1.0 ppm) at either gestational day (GD)10 or GD20, with longitudinal functional assessments and molecular endpoints conducted at term. Exposure at GD10 led to placental transcriptional changes at term that were consistent with markers in human preeclampsia, including reduced mmp10 and increased cd36, fzd1, and col1a1. O3 exposure, at both early and late gestation, induced a significant increase in maternal circulating soluble FMS-like tyrosine kinase-1 (sFlt-1), a known driver of preeclampsia. Otherwise, exposure to 0.3 ppm O3 at GD10 led to several late-stage cardiovascular outcomes in dams that were not evident in GD20-exposed dams, including elevated uterine artery resistance index and reduced cardiac output and stroke volume. GD10 O3 exposure proteomic profile in maternal hearts characterized by a reduction in proteins with essential roles in metabolism and mitochondrial function, whereas phosphoproteomic changes were consistent with pathways involved in cardiomyopathic responses. Thus, the developing placenta is an indirect target of inhaled O3 and systemic maternal cardiovascular abnormalities may be induced by O3 exposure at a specific window of gestation.

SUBMITTER: Garcia M

PROVIDER: S-EPMC8453811 | biostudies-literature | 2021 Jan

REPOSITORIES: biostudies-literature

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Early Gestational Exposure to Inhaled Ozone Impairs Maternal Uterine Artery and Cardiac Function.

Garcia Marcus M Salazar Raul R Wilson Thomas T Lucas Selita S Herbert Guy G Young Tamara T Begay Jessica J Denson Jesse L JL Zychowski Katherine K Ashley Ryan R Byrum Stephanie S Mackintosh Samuel S Bleske Barry E BE Ottens Andrew K AK Campen Matthew J MJ

Toxicological sciences : an official journal of the Society of Toxicology 20210101 1

Exposure to air pollutants such as ozone (O3) is associated with adverse pregnancy outcomes, including higher incidence of gestational hypertension, preeclampsia, and peripartum cardiomyopathy; however, the underlying mechanisms of this association remain unclear. We hypothesized that O3 exposures during early placental formation would lead to more adverse cardiovascular effects at term for exposed dams, as compared with late-term exposures. Pregnant Sprague Dawley rats were exposed (4 h) to eit ...[more]

PMID: 33146391

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Project description:ObjectivesTo examine the relationship of ophthalmic artery (OA) Doppler indices with uterine artery (UtA) Doppler indices, selected maternal hemodynamic parameters and gestational age, and to evaluate the intraobserver reproducibility of OA Doppler indices.MethodsThis was a prospective cohort study of women recruited between 11 + 0 and 23 + 6 weeks' gestation using a stratified and random sampling approach to ensure adequate distribution across the gestational-age range. OA pulsatility index (PI), first peak systolic velocity (PSV1), second peak systolic velocity (PSV2) and peak systolic velocity ratio (PSV ratio), calculated as PSV2/PSV1, were measured twice in each eye by the same observer. UtA-PI was also measured twice on each side by the same observer. Maternal hemodynamic assessment was undertaken using an ultrasonic cardiac output monitor (USCOM 1A). Pearson's and Spearman's rank correlation coefficients were used to assess the correlations between variables, and Bland-Altman plots were used to evaluate the intraobserver reproducibility of OA Doppler indices.ResultsOf 194 women invited to participate in the study, 169 were eligible for inclusion, of whom 16 were excluded following an obstetric ultrasound scan and a further three owing to inadequate or incomplete OA or UtA Doppler assessment, leaving 150 women in the final analysis. Log UtA-PI had a weak correlation with both OA-PI (r = -0.19 (95% CI, -0.34 to -0.03), P = 0.021) and OA-PSV ratio (r = 0.31 (95% CI, 0.15-0.45), P < 0.001). The correlation between gestational age and OA-PI was non-significant (r = 0.14 (95% CI, -0.03 to 0.29), P = 0.097), and that between gestational age and OA-PSV ratio was weak (r = -0.23 (95% CI, -0.38 to -0.07), P = 0.004), as opposed to the strong correlation between gestational age and UtA-PI (r = -0.68 (95% CI, -0.76 to -0.58), P < 0.001). No strong correlations were observed between OA-PI or OA-PSV ratio and maternal hemodynamic indices. The correlations were unaltered by adjustment for maternal age and body mass index. The intraobserver reproducibility of OA-PI and OA-PSV ratio in the same eye was high. The correlation between the right and left eyes was moderate for OA-PI (r = 0.63 (95% CI, 0.53-0.72), P < 0.001) and strong for OA-PSV ratio (r = 0.81 (95% CI, 0.75-0.86), P < 0.001).ConclusionsOA-PI and OA-PSV ratio had a weak or no correlation with UtA-PI and maternal hemodynamic parameters, meaning that they can be used as independent predictors for pre-eclampsia. Gestational age had no clinically relevant effect on OA-PI and OA-PSV ratio, suggesting that these indices could be measured without adjustment at any time between 11 and 23 weeks' gestation. OA Doppler indices had high intraobserver reproducibility and were strongly correlated between the right and left eyes. © 2025 The Author(s). Ultrasound in Obstetrics & Gynecology published by John Wiley & Sons Ltd on behalf of International Society of Ultrasound in Obstetrics and Gynecology.

Project description:BackgroundTrophoblastic invasion of the uterine spiral arteries substantially increases compliance to accommodate increased blood flow to the placenta. Failure of this process impedes uterine artery blood flow, and this may be detected by uterine artery Doppler flow studies. However, the clinical utility of uterine artery Doppler flow studies in the prediction of adverse pregnancy outcomes in a general population remains largely unknown.ObjectiveWe sought to determine the utility of early second-trimester uterine artery Doppler studies as a predictor of small-for-gestational-age neonates.Study designNulliparous women with a viable singleton pregnancy were recruited during their first trimester into an observational prospective cohort study at 8 institutions across the United States. Participants were seen at 3 study visits during pregnancy and again at delivery. Three indices of uterine artery Doppler flow (resistance index, pulsatility index, and diastolic notching) were measured in the right and left uterine arteries between 16 weeks 0 days' and 22 weeks 6 days' gestation. Test characteristics for varying thresholds in the prediction of small for gestational age (defined as birthweight <5th percentile for gestational age [Alexander growth curve]) were evaluated.ResultsUterine artery Doppler indices, birthweight, and gestational age at birth were available for 8024 women. Birthweight <5th percentile for gestational age occurred in 358 (4.5%) births. Typical thresholds for the uterine artery Doppler indices were all associated with birthweight <5th percentile for gestational age (P < .0001 for each), but the positive predictive values for these cutoffs were all <15% and areas under receiver operating characteristic curves ranged from 0.50-0.60. Across the continuous scales for these measures, the areas under receiver operating characteristic curves ranged from 0.56-0.62. Incorporating maternal age, early pregnancy body mass index, race/ethnicity, smoking status prior to pregnancy, chronic hypertension, and pregestational diabetes in the prediction model resulted in only modest improvements in the areas under receiver operating characteristic curves ranging from 0.63-0.66.ConclusionIn this large prospective cohort, early second-trimester uterine artery Doppler studies were not a clinically useful test for predicting small-for-gestational-age babies.

Project description:BackgroundStudies examining the effects of low-level gestational methylmercury exposure from fish consumption on infant neurobehavioral outcomes in the offspring are limited and inconclusive. Our objective was to examine the effects of low-level gestational exposure to methylmercury on neurobehavioral outcomes in early infancy.MethodsWe assessed neurobehavior of 344 infants at 5-weeks using the NICU Network Neurobehavioral Scale (NNNS). Gestational mercury exposure was measured as whole blood total mercury (WBTHg) in maternal and cord blood. We collected fish consumption information and estimated polyunsaturated fatty acid (PUFA) intake. We examined the association between gestational mercury exposure and NNNS scales using regression, adjusting for covariates.ResultsGeometric mean of maternal and cord WBTHg were 0.64 and 0.72 μg/L, respectively. Most mothers (84%) reported eating fish during pregnancy. Infants with higher prenatal mercury exposure showed increased asymmetric reflexes among girls (p=0.04 for maternal WBTHg and p=0.03 for cord WBTHg), less need for special handling during the assessment (p=0.03 for cord WBTHg) and a trend of better attention (p=0.054 for both maternal WBTHg and cord WBTHg). Similarly, infants born to mothers with higher fish consumption or estimated PUFA intake also had increased asymmetric reflexes and less need for special handling. In models simultaneously adjusted for WBTHg and fish consumption (or PUFA intake), the previously observed WBTHg effects were attenuated; and higher fish consumption (or PUFA intake) was significantly associated with less need for special handling.ConclusionsIn a cohort with low level mercury exposure and reporting low fish consumption, we found minimal evidence of mercury associated detrimental effects on neurobehavioral outcomes during early infancy. Higher prenatal mercury exposure was associated with more frequent asymmetric reflexes in girls. In contrast, infants with higher prenatal mercury exposure and those whose mothers consumed more fish had better attention and needed less special handling, which likely reflect the beneficial nutritional effects of fish consumption.

Dataset Information

Early Gestational Exposure to Inhaled Ozone Impairs Maternal Uterine Artery and Cardiac Function.

Publications

Early Gestational Exposure to Inhaled Ozone Impairs Maternal Uterine Artery and Cardiac Function.

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