Prenatal particulate matter exposure and mitochondrial mutational load at the maternal-fetal interface: Effect modification by genetic ancestry.
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ABSTRACT:
SUBMITTER: Brunst KJ
PROVIDER: S-EPMC9175302 | biostudies-literature | 2022 Jan
REPOSITORIES: biostudies-literature
Publications
Prenatal particulate matter exposure and mitochondrial mutational load at the maternal-fetal interface: Effect modification by genetic ancestry.
Brunst Kelly J KJ Hsu Hsiao-Hsien Leon HL Zhang Li L Zhang Xiang X Carroll Kecia N KN Just Allan A Coull Brent A BA Kloog Itai I Wright Robert O RO Baccarelli Andrea A AA Wright Rosalind J RJ
Mitochondrion 20211114
Prenatal ambient particulate matter (PM<sub>2.5</sub>) exposure impacts infant development and alters placental mitochondrial DNA abundance. We investigated whether the timing of PM<sub>2.5</sub> exposure predicts placental mitochondrial mutational load using NextGen sequencing in 283 multi-ethnic mother-infant dyads. We observed increased PM<sub>2.5</sub>exposure, particularly during mid- to late-pregnancy and among genes coding for NADH dehydrogenase and subunits of ATP synthase, was associate ...[more]
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Project description:BackgroundPrenatal ambient fine particulate matter (PM2.5) and maternal chronic psychosocial stress have independently been linked to changes in mithochondrial DNA copy number (mtDNAcn), a marker of mitochondrial response and dysfunction. Further, overlapping research shows sex-specific effects of PM2.5 and stress on developmental outcomes. Interactions among PM2.5, maternal stress, and child sex have not been examined in this context.MethodsWe examined associations among exposure to prenatal PM2.5, maternal lifetime traumatic stressors, and mtDNAcn at birth in a sociodemographically diverse pregnancy cohort (N=167). Mothers' daily exposure to PM2.5 over gestation was estimated using a satellite-based spatio-temporally resolved prediction model. Lifetime exposure to traumatic stressors was ascertained using the Life Stressor Checklist-Revised; exposure was categorized as high vs. low based on a median split. Quantitative real-time polymerase chain reaction (qPCR) was used to determine mtDNAcn in placenta and cord blood leukocytes. Bayesian Distributed Lag Interaction regression models (BDLIMs) were used to statistically model and visualize the PM2.5 timing-dependent pattern of associations with mtDNAcn and explore effect modification by maternal lifetime trauma and child sex.ResultsIncreased PM2.5 exposure across pregnancy was associated with decreased mtDNAcn in cord blood (cumulative effect estimate=-0.78; 95%CI -1.41, -0.16). Higher maternal lifetime trauma was associated with reduced mtDNAcn in placenta (β=-0.33; 95%CI -0.63, -0.02). Among women reporting low trauma, increased PM2.5 exposure late in pregnancy (30-38weeks gestation) was significantly associated with decreased mtDNAcn in placenta; no significant association was found in the high trauma group. BDLIMs identified a significant 3-way interaction between PM2.5, maternal trauma, and child sex. Specifically, PM2.5 exposure between 25 and 40weeks gestation was significantly associated with increased placental mtDNAcn among boys of mothers reporting high trauma. In contrast, PM2.5 exposure in this same window was significantly associated with decreased placental mtDNAcn among girls of mothers reporting low trauma. Similar 3-way interactive effects were observed in cord blood.ConclusionsThese results indicate that joint exposure to PM2.5 in late pregnancy and maternal lifetime trauma influence mtDNAcn at the maternal-fetal interface in a sex-specific manner. Additional studies will assist in understanding if the sex-specific patterns reflect distinct pathophysiological processes in addition to mitochondrial dysfunction.
| S-EPMC6094933 | biostudies-literature
Project description:Fine particulate matter (PM2.5) potentiates in utero oxidative stress influencing fetal development while antioxidants have potential protective effects. We examined associations among prenatal PM2.5, maternal antioxidant intake, and childhood wheeze in an urban pregnancy cohort (n = 530). Daily PM2.5 exposure over gestation was estimated using a satellite-based spatiotemporally resolved model. Mothers completed the modified Block98 food frequency questionnaire. Average energy-adjusted percentile intake of β-carotene, vitamins (A, C, E), and trace minerals (zinc, magnesium, selenium) constituted an antioxidant index (AI). Maternal-reported child wheeze was ascertained up to 4.1 ± 2.8 years. Bayesian distributed lag interaction models (BDLIMs) were used to examine time-varying associations between prenatal PM2.5 and repeated wheeze (≥2 episodes) and effect modification by AI, race/ethnicity, and child sex. Covariates included maternal age, education, asthma, and temperature. Women were 39% Black and 33% Hispanic, 36% with ≤high school education; 21% of children had repeated wheeze. Higher AI was associated with decreased wheeze in Blacks (OR = 0.37 (0.19-0.73), per IQR increase). BDLIMs identified a sensitive window for PM2.5 effects on wheeze among boys born to Black mothers with low AI (at 33-40 weeks gestation; OR = 1.74 (1.19-2.54), per µg/m3 increase in PM2.5). Relationships among prenatal PM2.5, antioxidant intake, and child wheeze were modified by race/ethnicity and sex.
| S-EPMC8868511 | biostudies-literature
Project description:BackgroundFetal growth restriction (FGR) is not only a major determinant of perinatal morbidity and mortality but also leads to adverse health effects in later life. Over the past decade, numerous studies have indicated that maternal exposure to ambient air pollution has been a risk factor for abnormal fetal growth in developed countries where PM2.5 levels are relatively low. However, studies in highly polluted regions, such as China, and studies that rely on assessments in utero are scarce.MethodsA total of 7965 women were selected from 11,441 women from the Shanghai Maternity and Infant Living Environment (SMILE) cohort who were pregnant between January 1, 2014, and April 30, 2015. From January 1, 2014, to April 30, 2015, weekly average PM2.5 values from 53 monitors were calculated and the inverse distance weighted (IDW) method was used to create a Shanghai pollution surface map according to the participants residential addresses. Individual exposure was the average PM2.5 value of every gestational week between the first gestational week and one week before the ultrasound measurement date (the range of measurements per participant was 1 to 10). Repeated fetal ultrasound measurements during gestational weeks 14~40 were selected. The estimated fetal weight (EFW) was calculated by biparietal diameter (BPD), abdominal circumference (AC), and femur length (FL) formulas. In total, 29,926 ultrasound measurements were analysed. Demographic variables, other pollutants (SO2, NO2, PM10 and O3) and relative humidity and temperature were controlled for potential confounding through generalized estimating equations (GEE).ResultsThe full model showed that with each 10 μg/m3 increase in PM2.5 exposure, the means (mm) of AC, BPD, FL decreased by 5.48 (- 9.06, - 1.91), 5.57 (- 6.66, - 4.47), and 5.47 (- 6.39, - 4.55), respectively; the mean EFW decreased by 14.49 (- 16.05, - 13.49) grams by Hadlock's third formula and 13.56 (- 14.71, - 12.50) grams by Shepard's formula with each 10 μg/m3 increase in PM2.5 exposure.ConclusionsA negative correlation existed between maternal PM2.5 exposure during pregnancy and fetal growth indicators, which may increase the risk of fetal growth restriction.
| S-EPMC6524254 | biostudies-literature
Project description:BackgroundFetal growth has been known to be associated with particulate matter (PM) air pollution during gestation. Given that regular working may deviate outdoor air pollution exposure, the association between air pollution and fetal growth restriction can be different across maternal working status. This study was to assess possible effect modification by maternal employment in the association between exposure to PM during pregnancy and fetal growth restriction.MethodsUsing hourly PM less than or equal to 10 and 2.5 μm in diameter (PM10 and PM2.5) regulatory monitoring data for 2001-2012 and 2008-2012, respectively, and birth certificate data for 2002-2012, we computed maternal exposures with district-level averages of PM10 and PM2.5 during one year before birth, entire pregnancy, and the 1st, 2nd and 3rd trimesters. The outcomes of fetal growth restriction were assessed by small for gestational age (SGA, weighted <10th percentile in the same gestational age) as well as low birth weight (LBW, < 2.5 kg) at term. We performed logistic regression to examine the association between PM and each of fetal growth restriction outcomes adjusting for individual risk factors. For effect modification by maternal employment, we estimated adjusted odds ratio (OR) of SGA or LBW for interquartile (IQR) increases in PM10 or PM2.5 stratified by employed and non-employed mothers. We also computed relative excess risk due to interaction (RERI) to investigate additive interaction.ResultsAmong 824,011 singleton term births, 34.0% (279,856) were employed and 66.0% (544,155) were non-employed mothers. Proportions of LBW were 1.5% in employed and 1.6% in non-employed (P < 0.001). SGA occurred in 12.7% of employed and 12.8% of non- employed (P = 0.124) mothers. For non-employed mothers, we observed increased odds of SGA per IQR increase in PM10 for one year before birth (OR = 1.02, 95% confidence intervals (CI): 1.00-1.04, P = 0.028). ORs of SGA for full pregnancy period and the 3rd trimester were also positive but did not reach statistical significance. We did not observe positive association for PM2.5. RERI was not significant both for PM10 and PM2.5.ConclusionsWe did not observe evidence of effect modification by maternal employment in the association between ambient PM and fetal growth restriction. Future studies using more refined exposure measures should confirm this finding.
| S-EPMC6632189 | biostudies-literature
Project description:Prenatal maternal stress (PNMS) determines lifetime mental and physical health. Here, we show in rats that PNMS has consequences for placental function and fetal brain development across four generations (F0-F3). Using a systems biology approach, comprehensive DNA methylation (DNAm), miRNA, and mRNA profiling revealed a moderate impact of PNMS in the F1 generation, but drastic changes in F2 and F3 generations, suggesting compounding effects of PNMS with each successive generation. Both maternal and placental miRNA gene targets included de novo DNA methyltransferases, indicating robust PNMS-induced disruption in the complex epigenetic regulatory network between miRNAs and DNAm. Transgenerational programming mainly involved genes and biological pathways associated with neurological and psychiatric diseases which were linked to maternal-fetal crosstalk facilitated by the placenta. The highly correlated placenta-brain profiles support the use of placenta as a noninvasive biomarker resource to predict pathological changes in the neonatal brain. The transgenerational persistence of critical DNAm, miRNA and mRNA signatures may explain familial non-genetic disease risks.
| S-EPMC11723964 | biostudies-literature
Project description:IntroductionIn utero particulate matter exposure produces oxidative stress that impacts cellular processes that include telomere biology. Newborn telomere length is likely critical to an individual's telomere biology; reduction in this initial telomere setting may signal increased susceptibility to adverse outcomes later in life. We examined associations between prenatal particulate matter with diameter ≤2.5 µm (PM2.5) and relative leukocyte telomere length (LTL) measured in cord blood using a data-driven approach to characterize sensitive windows of prenatal PM2.5 effects and explore sex differences.MethodsWomen who were residents of Mexico City and affiliated with the Mexican Social Security System were recruited during pregnancy (n = 423 for analyses). Mothers' prenatal exposure to PM2.5 was estimated based on residence during pregnancy using a validated satellite-based spatio-temporally resolved prediction model. Leukocyte DNA was extracted from cord blood obtained at delivery. Duplex quantitative polymerase chain reaction was used to compare the relative amplification of the telomere repeat copy number to single gene (albumin) copy number. A distributed lag model incorporating weekly averages for PM2.5 over gestation was used in order to explore sensitive windows. Sex-specific associations were examined using Bayesian distributed lag interaction models.ResultsIn models that included child's sex, mother's age at delivery, prenatal environmental tobacco smoke exposure, pre-pregnancy BMI, gestational age, birth season and assay batch, we found significant associations between higher PM2.5 exposure during early pregnancy (4-9 weeks) and shorter LTL in cord blood. We also identified two more windows at 14-19 and 34-36 weeks in which increased PM2.5 exposure was associated with longer LTL. In stratified analyses, the mean and cumulative associations between PM2.5 and shortened LTL were stronger in girls when compared to boys.ConclusionsIncreased PM2.5 during specific prenatal windows was associated with shorter LTL and longer LTL. PM2.5 was more strongly associated with shortened LTL in girls when compared to boys. Understanding sex and temporal differences in response to air pollution may provide unique insight into mechanisms.
| S-EPMC6511309 | biostudies-literature
Project description:BackgroundEvidence links gestational exposure to particulate matter with an aerodynamic diameter of less than 2.5 μm (PM2.5) with changes in leukocyte telomere length in cord blood with some studies showing sex-specific effects. PM2.5 exposure in utero increases oxidative stress, which can impact telomere biology. Thus, maternal antioxidant intakes may also modify the particulate air pollution effects.MethodsWe examined associations among prenatal PM2.5 exposure and newborn relative leukocyte telomere length (rLTL), and the modifying effects of maternal antioxidant intake and infant sex. We estimated daily PM2.5 exposures over gestation using a validated spatiotemporally resolved satellite-based model. Maternal dietary and supplemental antioxidant intakes over the prior three months were ascertained during the second trimester using the modified Block98 food frequency questionnaire; high and low antioxidant intakes were categorized based on a median split. We employed Bayesian distributed lag interaction models (BDLIMs) to identify both sensitive windows of exposure and cumulative effect estimates for prenatal PM2.5 exposure on newborn rLTL, and to examine effect modification by maternal antioxidant intakes. A 3-way interaction between PM2.5, maternal antioxidant intake and infant sex was also explored.ResultsFor the main effect of PM2.5, BDLIMs identified a sensitive window at 12-20 weeks gestation for the association between increased prenatal PM2.5 exposure and shorter newborn rLTL and a cumulative effect of PM2.5 over gestation on newborn telomere length [cumulative effect estimate (CEE) = -0.29 (95% CI -0.49 to -0.10) per 1μg/m3 increase in PM2.5]. In models examining maternal antioxidant intake effects, BDLIMs found that children born to mothers reporting low antioxidant intakes were most vulnerable [CEE of low maternal antioxidant intake = -0.31 (95% CI -0.55 to -0.06) vs high maternal antioxidant intake = -0.07 (95% CI -0.34 to 0.17) per 1μg/m3 increase in PM2.5]. In exploratory models examining effect modification by both maternal antioxidant intakes and infant sex, the cumulative effect remained significant only in boys whose mothers reported low antioxidant intakes [CEE = -0.38 (95% CI -0.80 to -0.004)]; no sensitive windows were identified in any group.ConclusionsPrenatal PM2.5 exposure in mid-gestation was associated with reduced infant telomere length. Higher maternal antioxidant intakes mitigated these effects.
| S-EPMC7844769 | biostudies-literature
Project description:BackgroundWhile strong evidence supports adverse maternal and offspring consequences of air pollution, mechanisms that involve the placenta, a key part of the intrauterine environment, are largely unknown. Previous studies of air pollution and placental gene expression were small candidate gene studies that rarely considered prenatal windows of exposure or the potential role of offspring sex. We examined overall and sex-specific associations of prenatal exposure to fine particulate matter (PM2.5) with genome-wide placental gene expression.MethodsParticipants with placenta samples, collected at birth, and childhood health outcomes from CANDLE (Memphis, TN) (n = 776) and GAPPS (Seattle, WA) (n = 205) cohorts of the ECHO-PATHWAYS Consortium were included in this study. PM2.5 exposures during trimesters 1, 2, 3, and the first and last months of pregnancy, were estimated using a spatiotemporal model. Cohort-specific linear adjusted models were fit for each exposure window and expression of >11,000 protein coding genes from paired end RNA sequencing data. Models with interaction terms were used to examine PM2.5-offspring sex interactions. False discovery rate (FDR < 0.10) was used to correct for multiple testing.ResultsMean PM2.5 estimate was 10.5-10.7 μg/m3 for CANDLE and 6.0-6.3 μg/m3 for GAPPS participants. In CANDLE, expression of 13 (11 upregulated and 2 downregulated), 20 (11 upregulated and 9 downregulated) and 3 (2 upregulated and 1 downregulated) genes was associated with PM2.5 in the first trimester, second trimester, and first month, respectively. While we did not find any statistically significant association, overall, between PM2.5 and gene expression in GAPPS, we found offspring sex and first month PM2.5 interaction for DDHD1 expression (positive association among males and inverse association among females). We did not observe PM2.5 and offspring sex interactions in CANDLE.ConclusionIn CANDLE, but not GAPPS, we found that prenatal PM2.5 exposure during the first half of pregnancy is associated with placental gene expression.
| S-EPMC9235522 | biostudies-literature
Project description:Introduction Encephalomalacia in a developing fetus is a rare and devastating neurological finding on radiologic imaging. Maternal diabetic ketoacidosis (DKA) can lead to metabolic and vascular derangements which can cause fetal encephalomalacia. Case We report the case of a 27-year-old pregnant woman with White's Class C diabetes mellitus who presented in the 25th week of gestation with DKA. Four weeks after her discharge, marked fetal cerebral ventriculomegaly was noted on ultrasound. A subsequent fetal magnetic resonance imaging (MRI) demonstrated extensive, symmetric cystic encephalomalacia, primarily involving both cerebral hemispheres. The pregnancy was continued with close fetal and maternal surveillance. The patient underwent a repeat cesarean delivery in her 37th week. The infant had a 1 month neonatal intensive care unit stay with care rendered by a multiple disciplinary team of pediatric subspecialists. The postnatal course was complicated by global hypotonia, poor feeding, delayed development and ultimately required anticonvulsants for recurrent seizures. He died at the age of 9 months from aspiration during a seizure. Discussion Although the maternal mortality from DKA has declined, DKA still confers significant neurological fetal morbidity to its survivors.
| S-EPMC4239142 | biostudies-other
Project description: Not available
| S-EPMC7203721 | biostudies-literature