Placental mtDNA Content Research Articles

Transient Early Fine Motor Abnormalities in Infants Born to COVID-19 Mothers Are Associated With Placental Hypoxia and Ischemia

Background: Long-term effects of Coronavirus Disease 2019 (COVID-19) on infants born to infected mothers are not clear. Fine motor skills are crucial for the development of infant emotional regulation, learning ability and social skills.Methods: Clinical information of 100 infants born to 98 mothers (COVID-19 n = 31, non-COVID-19 n = 67) were collected. Infants were follow-up up to 9 months post-partum. The placental tissues were examined for SARS-CoV-2 infection, pathological changes, cytokines, and mtDNA content.Results: Decreased placental oxygen and nutrient transport capacity were found in infected pregnant women. Increased IL-2, IL-6, TNF-α, and IFN-γ were detected in trophoblast cells and maternal blood of COVID-19 placentas. Elevated early fine motor abnormal-ities and increased serum TNI (troponin I) levels at delivery were observed in infants born to mothers with COVID-19. Increased abnormal mitochondria and elevated mtDNA content were found in the placentas from infected mothers. The placental mtDNA content of three infants with abnormal DDST were increased by 4, 7, and 10%, respectively, compared to the mean of the COVID-19 group. The Maternal Vascular Malperfusion (MVM), elevated cytokines and increased placental mtDNA content in mothers with COVID-19 might be associated with transient early fine motor abnormalities in infants. These abnormalities are only temporary, and they could be corrected by daily training.Conclusions: Babies born to COVID-19 mothers with mild symptoms appeared to have little or no excess long-term risks of abnormal physical and neurobehavioral development as compared with the infants delivered by non-COVID-19 mothers.

Placental mitochondrial DNA content is associated with childhood intelligence

BackgroundDevelopmental processes in the placenta and the fetal brain are shaped by the similar biological signals. Evidence accumulates that adaptive responses of the placenta may influence central nervous system development. We hypothesize that placental mtDNA content at birth is associated with intelligence in childhood. In addition, we investigate if intra-pair differences in mtDNA content are associated with intra-pair differences in intelligence.MethodsRelative mtDNA content was measured using qPCR in placental tissue of 375 children of the East Flanders Prospective Twin Survey. Intelligence was assessed with the Wechsler Intelligence Scale for Children-Revised (WISC-R) between 8 and 15 years old. We accounted for sex, gestational age, birth weight, birth year, zygosity and chorionicity, cord insertion, age at measurement, indicators of socioeconomic status, smoking during pregnancy, and urban environment.ResultsIn multivariable adjusted mixed modelling analysis, each doubling in placental mtDNA content was associated with 2.0 points (95% CI 0.02 to 3.9; p = 0.05) higher total and 2.3 points (95% CI 0.2 to 4.3; p = 0.03) higher performance IQ in childhood. We observed no association between mtDNA content and verbal intelligence. Intra-pair differences in mtDNA content and IQ were significantly (p = 0.01) correlated in monozygotic-monochorionic twin pairs, showing that the twin with the highest mtDNA content was 1.9 times more likely (p = 0.05) to have the highest IQ. This was not observed in dichorionic twin pairs.ConclusionsWe provide the first evidence that placental mtDNA content is associated with childhood intelligence. This emphasizes the importance of placental mitochondrial function during in utero life on fetal brain development with long-lasting consequences.

Regulating role of fetal thyroid hormones on placental mitochondrial DNA methylation: epidemiological evidence from the ENVIRONAGE birth cohort study

BackgroundFetal development largely depends on thyroid hormone availability and proper placental function with an important role played by placental mitochondria. The biological mechanisms by which thyroid hormones exert their effects on mitochondrial function are not well understood. We investigated the role of fetal thyroid hormones on placental mitochondrial DNA (mtDNA) content and mtDNA methylation. We collected placental tissue and cord blood from 305 mother–child pairs that were enrolled between February 2010 and June 2014 in the ENVIRONAGE (ENVIRonmental influence ON early AGEing) birth cohort (province of Limburg, Belgium). Placental mtDNA content was determined by qPCR and placental mtDNA methylation by bisulfite-pyrosequencing in two regions, i.e., the D-loop control region and 12S ribosomal RNA (MT-RNR1). The levels of free thyroid hormones (FT3, FT4) and thyroid-stimulating hormone (TSH) were measured in cord blood.ResultsCord blood FT3 and FT4 were inversely associated with placental mtDNA methylation at the MT-RNR1 (p ≤ 0.01) and D-loop (p ≤ 0.05) regions, whereas a positive association was observed for both hormones with placental mtDNA content (p ≤ 0.04). Assuming causality, we estimated that MT-RNR1 and D-loop methylation mediated, respectively, 77% [indirect effect +14.61% (95% CI 2.64 to 27.98%, p = 0.01)] and 47% [indirect effect +8.60% (95% CI 1.23 to 16.50%, p = 0.02] of the positive association between FT3 and placental mtDNA content. Mediation models with FT4 gave similar results but the estimated effect proportions were smaller compared with those of FT3 (54% and 24%, respectively).ConclusionsWe showed that epigenetic modification at specific loci of the mitochondrial genome could intervene with the thyroid-dependent regulation of mitochondrial DNA copy numbers.

Neonatal exposure to environmental pollutants and placental mitochondrial DNA content: A multi-pollutant approach

BackgroundPlacental mitochondrial DNA (mtDNA) content can be indicative of oxidative damage to the placenta during fetal development and is responsive to external stressors. In utero exposure to environmental pollutants that may influence placental mtDNA needs further exploration. ObjectivesWe evaluated if placental mtDNA content is altered by environmental pollution in newborns and identified pollutants independently associated to alterations in placental mtDNA content. MethodsmtDNA content was measured in placental tissue of 233 newborns. Four perfluoroalkyl compounds and nine organochlorine compounds were quantified in cord blood plasma samples and six toxic metals in whole cord blood. We first applied a LASSO (least absolute shrinkage and selection operator) penalized regression model to identify independent associations between environmental pollutants and placental mtDNA content, without penalization of several covariates. Then adjusted estimates were obtained using an ordinary least squares (OLS) regression model evaluating the pollutants' association with placental mtDNA content, adjusted for several covariates. ResultsBased on LASSO penalized regression, oxychlordane, p,p′-dichlorodiphenyldichloroethylene, β-hexachlorocyclohexane, perfluorononanoic acid, arsenic, cadmium and thallium were identified to be independently associated with placental mtDNA content. The OLS model showed a higher placental mtDNA content of 2.71% (95% CI: 0.3 to 5.2%; p=0.03) and 1.41% (0.1 to 2.8%, p=0.04) for a 25% concentration increase of respectively cord blood β-hexachlorocyclohexane and arsenic. For a 25% concentration increase of cord blood thallium, a 4.88% lower placental mtDNA content (95% CI: -9.1 to −0.5%, p=0.03) was observed. ConclusionIn a multi-pollutant approach, low fetal exposure levels of environmental organic and inorganic pollutants might compromise placental mitochondrial function as exemplified in this study by alterations in mtDNA content.

Prenatal ambient air pollution exposure, infant growth and placental mitochondrial DNA content in the INMA birth cohort

BackgroundThe association between prenatal air pollution exposure and postnatal growth has hardly been explored. Mitochondrial DNA (mtDNA), as a marker of oxidative stress, and growth at birth can play an intermediate role in this association. ObjectiveIn a subset of the Spanish birth cohort INMA we assessed first whether prenatal nitrogen dioxide (NO2) exposure is associated with infant growth. Secondly, we evaluated whether growth at birth (length and weight) could play a mediating role in this association. Finally, the mediation role of placental mitochondrial DNA content in this association was assessed. MethodsIn 336 INMA children, relative placental mtDNA content was measured. Land-use regression models were used to estimate prenatal NO2 exposure. Infant growth (height and weight) was assessed at birth, at 6 months of age, and at 1 year of age. We used multiple linear regression models and performed mediation analyses. The proportion of mediation was calculated as the ratio of indirect effect to total effect. ResultsPrenatal NO2 exposure was inversely associated with all infant growth parameters. A 10µg/m³ increment in prenatal NO2 exposure during trimester 1 of pregnancy was significantly inversely associated with height at 6 months of age (−6.6%; 95%CI: −11.4, −1.9) and weight at 1 year of age (−4.2%; 95%CI: −8.3, −0.1). These associations were mediated by birth length (31.7%; 95%CI: 34.5, 14.3) and weight (53.7%; 95%CI: 65.3, −0.3), respectively. Furthermore, 5.5% (95%CI: 10.0, −0.2) of the association between trimester 1 NO2 exposure and length at 6 months of age could be mediated by placental mtDNA content. ConclusionsOur results suggest that impaired fetal growth caused by prenatal air pollution exposure can lead to impaired infant growth during the first year of life. Furthermore, molecular adaptations in placental mtDNA are associated with postnatal consequences of air pollution induced alterations in growth.

Placental mtDNA content and environmental exposure: a multipollutant approach

Introduction: Exposure to environmental pollutants might affect placental functioning and thus also fetal growth. Placental mitochondrial DNA (mtDNA) content can be indicative of oxidative damage to the placenta during fetal development. However, discriminating between the relevant exposures that influence placental mtDNA from a mixture of pollutants is currently lacking. Methods: Four perfluoralkyl compounds, ten persistent organic pollutants and six heavy metals were quantified in cord blood serum samples of 239 newborns. mtDNA content was measured in placental tissue using qPCR. We first applied an adaptive LASSO (least absolute shrinkage and selection operator) penalized regression model to identify independent associations between environmental pollutants and placental mtDNA content, when adjusting for mother newborn-characteristics: newborn’s sex, gestational age, birth weight, season of birth, maternal age, education, pre-pregnancy BMI, parity, smoking during pregnancy and ethnicity which were not penalized. Then adjusted estimates were obtained using unpenalized multiple-exposure linear regression models evaluating the association with placental mtDNA content. Results: Based on adaptive LASSO penalized regression, perfluorononanoic acid (PFNA), perfluorohexane sulfonic acid (PFHXS), p,p’-DDE, lindane, PCB146, PCB153, thallium and arsenic were identified to be independently predictive of placental mtDNA content. In an adjusted multiple exposure model we observed a significant percent change (95% CI) in mtDNA content for every doubling of the following pollutants: 10% increase (1 to 19%, p=0.02) mtDNA content for lindane, 15% decrease (-27 to -2%, p=0.02) for thallium and 5% increase (1 to 10%, p=0.02) for arsenic. Conclusion: In a multi-pollutant exposure model, environmental pollutants compromise placental mitochondrial function as exemplified by mtDNA content.

Prenatal air pollution exposure, infant growth and placental mtDNA content in the INMA birth cohort

Background: Prenatal air pollution exposure has been linked to adverse birth outcomes, but the effect on postnatal growth has hardly been explored. Mitochondria are sensitive to environmental toxic...

Prenatal Air Pollution and Reduced Birth Weight: Decline in Placental Mitochondria as a Potential Mechanism

Strong epidemiological evidence links prenatal exposure to ambient air pollution and outcomes including low birth weight, intrauterine growth restriction, and preterm birth.1,2 A new study finds evidence that the association between prenatal air pollution exposure and reduced birth weight may be mediated in part by a decline in the mitochondrial content of the placenta.3 During pregnancy, the placenta supports the nourishment, growth, and development of the fetus, and mitochondria within the cells of the placenta are essential to these processes.4 Mitochondria, the cellular organelles that regulate energy production, are easily damaged by reactive oxygen species generated by oxidative stress. Mitochondrial DNA (mtDNA) is inherently more vulnerable to oxidative stress than nuclear DNA because it lacks protective and repair mechanisms.4 Such damage could ultimately lead to diminished numbers of mitochondria and impaired energy flow, which would undermine cellular functions.5 Low birth weight, intrauterine growth restriction, and preterm birth are all strongly associated with exposure to air pollution. A reduction in placental levels of mitochondrial DNA could help explain why. Air pollution is known to induce oxidative stress; thus, it could adversely affect placental mitochondria and thereby impair the ability of the placenta to support the growing fetus.3,5 A potential consequence of placental impairment is low birth weight, which in turn is associated with other detrimental health outcomes in children, both short- and long-term.2 The current study draws on data collected through two independent birth cohort studies conducted in Europe: Infancia y Medio Ambiente (INMA) in Spain, and Environmental Influence on Ageing (ENVIRONAGE) in Belgium. Demographic data and information on smoking status, residence location, and pre-pregnancy body mass index were obtained for all participants, and birth records were used to gather information on newborns’ sex, birth weight, gestational age, and delivery. For one-quarter of the INMA participants and all ENVIRONAGE participants, placentas were collected at birth, and their nuclear DNA and mtDNA content was measured. Ambient air pollution exposure for both cohorts was represented by nitrogen dioxide (NO2) concentrations. Exposures were averaged for each trimester and for the whole pregnancy. The current statistical analyses focused on 376 INMA participants and 550 ENVIRONAGE participants. The researchers found that prenatal NO2 exposures overall and for each trimester were inversely associated with both placental mtDNA content and birth weight. Specifically, each 10-μg/m3 increase in NO2 over the course of pregnancy was associated with an average 48-g reduction in birth weight across both cohorts.3 The association between NO2 and birth weight was stronger in the INMA cohort than in the ENVIRONAGE cohort (an average 66-g versus 20-g reduction), which could be explained by differences in factors such as exposure assessment methods, population characteristics, and study design.3 For instance, for the INMA cohort, NO2 was measured by outdoor passive samplers distributed throughout the study areas, with land use regression models accounting for residential location. The NO2 exposure estimates in the ENVIRONAGE cohort depended on residential address, satellite data, and a dispersion model that incorporated ground-based data. Prenatal NO2 exposures were also inversely associated with placental mtDNA content, and placental mtDNA and birth weight were positively correlated. Based on these results, the authors concluded that placental mtDNA content may mediate the relationship between prenatal NO2 exposure and birth weight.3 “We saw very clearly that the mtDNA was indeed related to birth weight,” says lead investigator Tim Nawrot, an assistant professor of environmental epidemiology at Hasselt University in Belgium. “Babies with a lower mtDNA content in the placenta showed a lower birth weight in both cohorts.” The authors point to the lack of data on indoor air exposures—which also have been associated with changes in birth weight—as a limitation of the study. “Overall, I see this study as an important piece of the puzzle as far as the weight of evidence on air pollution and pregnancy outcomes,” says David Stieb, a public health physician and epidemiologist at Health Canada, who was not involved in the study. “There have been dozens of epidemiological studies looking at these associations, and there does seem to be a fairly consistent signal now, especially for air pollution and reduced birth weight.” With limited evidence for the mechanisms that could explain that association, “this study could definitely help fill the gap,” says Stieb. The results will need to be confirmed through further epidemiological investigations, long-term prospective studies, and experimental research. “We will certainly look at whether the mitochondrial function in the placenta is related to future aspects of development,” says Nawrot. “What we want to establish is whether the mitochondrial-related weight reduction in early life is related to disease development later in life.”

Prenatal air pollution exposure and growth: The role of placental mtDNA content

Background and aims In recent years, evidence has shown that prenatal trafficrelated air pollution exposure influences fetal growth. Changes in mitochondrial DNA (mtDNA) content may represent a biologically relevant endpoint on the mechanisms underlying the association between air pollution and fetal growth restrictions. In this study, we aimed to assess the role of placental mtDNA content on the association of prenatal NO2 exposure with fetal growth assessed by ultrasound measurements.

Prenatal Ambient Air Pollution, Placental Mitochondrial DNA Content, and Birth Weight in the INMA (Spain) and ENVIRONAGE (Belgium) Birth Cohorts.

Background:Mitochondria are sensitive to environmental toxicants due to their lack of repair capacity. Changes in mitochondrial DNA (mtDNA) content may represent a biologically relevant intermediate outcome in mechanisms linking air pollution and fetal growth restriction.Objective:We investigated whether placental mtDNA content is a possible mediator of the association between prenatal nitrogen dioxide (NO2) exposure and birth weight.Methods:We used data from two independent European cohorts: INMA (n = 376; Spain) and ENVIRONAGE (n = 550; Belgium). Relative placental mtDNA content was determined as the ratio of two mitochondrial genes (MT-ND1 and MTF3212/R3319) to two control genes (RPLP0 and ACTB). Effect estimates for individual cohorts and the pooled data set were calculated using multiple linear regression and mixed models. We also performed a mediation analysis.Results:Pooled estimates indicated that a 10-μg/m3 increment in average NO2 exposure during pregnancy was associated with a 4.9% decrease in placental mtDNA content (95% CI: –9.3, –0.3%) and a 48-g decrease (95% CI: –87, –9 g) in birth weight. However, the association with birth weight was significant for INMA (–66 g; 95% CI: –111, –23 g) but not for ENVIRONAGE (–20 g; 95% CI: –101, 62 g). Placental mtDNA content was associated with significantly higher mean birth weight (pooled analysis, interquartile range increase: 140 g; 95% CI: 43, 237 g). Mediation analysis estimates, which were derived for the INMA cohort only, suggested that 10% (95% CI: 6.6, 13.0 g) of the association between prenatal NO2 and birth weight was mediated by changes in placental mtDNA content.Conclusion:Our results suggest that mtDNA content can be one of the potential mediators of the association between prenatal air pollution exposure and birth weight.Citation:Clemente DB, Casas M, Vilahur N, Begiristain H, Bustamante M, Carsin AE, Fernández MF, Fierens F, Gyselaers W, Iñiguez C, Janssen BG, Lefebvre W, Llop S, Olea N, Pedersen M, Pieters N, Santa Marina L, Souto A, Tardón A, Vanpoucke C, Vrijheid M, Sunyer J, Nawrot TS. 2016. Prenatal ambient air pollution, placental mitochondrial DNA content, and birth weight in the INMA (Spain) and ENVIRONAGE (Belgium) birth cohorts. Environ Health Perspect 124:659–665; http://dx.doi.org/10.1289/ehp.1408981

Placental mitochondrial methylation and exposure to airborne particulate matter in the early life environment: An ENVIRONAGE birth cohort study

Most research to date has focused on epigenetic modifications in the nuclear genome, with little attention devoted to mitochondrial DNA (mtDNA). Placental mtDNA content has been shown to respond to environmental exposures that induce oxidative stress, including airborne particulate matter (PM). Damaged or non-functioning mitochondria are specifically degraded through mitophagy, exemplified by lower mtDNA content, and could be primed by epigenetic modifications in the mtDNA. We studied placental mtDNA methylation in the context of the early life exposome. We investigated placental tissue from 381 mother-newborn pairs that were enrolled in the ENVIRONAGE birth cohort. We determined mtDNA methylation by bisulfite-pyrosequencing in 2 regions, i.e., the D-loop control region and 12S rRNA (MT-RNR1), and measured mtDNA content by qPCR. PM2.5 exposure was calculated for each participant's home address using a dispersion model. An interquartile range (IQR) increment in PM2.5 exposure over the entire pregnancy was positively associated with mtDNA methylation (MT-RNR1: +0.91%, P = 0.01 and D-loop: +0.21%, P = 0.05) and inversely associated with mtDNA content (relative change of −15.60%, P = 0.001) in placental tissue. mtDNA methylation was estimated to mediate 54% [P = 0.01 (MT-RNR1)] and 27% [P = 0.06 (D-loop)] of the inverse association between PM2.5 exposure and mtDNA content. This study provides new insight into the mechanisms of altered mitochondrial function in the early life environment. Epigenetic modifications in the mitochondrial genome, especially in the MT-RNR1 region, substantially mediate the association between PM2.5 exposure during gestation and placental mtDNA content, which could reflect signs of mitophagy and mitochondrial death.

Mitochondrial DNA in Placenta: Associations with Fetal Growth and Superoxide Dismutase Activity

Background: Prenatal growth restraint is associated with increased oxidative stress - as judged by mitochondrial dysfunction - in pregnancies complicated by preeclampsia or diabetes, but it is uncertain whether this is also the case in uncomplicated pregnancies. We assessed the link between fetal growth restraint and placental mitochondrial dysfunction, as reflected by changes in mitochondrial DNA (mtDNA) content and superoxide dismutase (SOD) activity. Methods: After uncomplicated pregnancies, placentas (n = 48) were collected at term delivery of singleton infants who were appropriate for gestational age (AGA) or small for gestational age (SGA) (n = 24 in each subgroup). Placental mtDNA content was assessed by real-time PCR, placental SOD activity by colorimetry, and citrate synthase activity - to determine mitochondrial mass - by the spectrophotometric method. Results: Placentas of SGA infants had a lower mtDNA content (p = 0.015) and a higher SOD activity (p = 0.001) than those of AGA controls. These differences were maintained after normalization of the mtDNA content by citrate synthase activity. In placentas of SGA infants, there was a negative association between mtDNA content and SOD activity (r = -0.58, p = 0.008). Conclusions: Fetal growth restraint is accompanied by adaptive changes in the mitochondrial function of the placenta, also in uncomplicated pregnancies.

Maternal calorie restriction modulates placental mitochondrial biogenesis and bioenergetic efficiency: putative involvement in fetoplacental growth defects in rats

Low birth weight is associated with an increased risk for developing type 2 diabetes and metabolic diseases. The placental capacity to supply nutrients and oxygen to the fetus represents the main determiner of fetal growth. However, few studies have investigated the effects of maternal diet on the placenta. We explored placental adaptive proteomic processes implicated in response to maternal undernutrition. Rat term placentas from 70% food-restricted (FR30) mothers were used for a proteomic screen. Placental mitochondrial functions were evaluated using molecular and functional approaches, and ATP production was measured. FR30 drastically reduced placental and fetal weights. FR30 placentas displayed 14 proteins that were differentially expressed, including several mitochondrial proteins. FR30 induced a marked increase in placental mtDNA content and changes in mitochondrial functions, including modulation of the expression of genes implicated in biogenesis and bioenergetic pathways. FR30 mitochondria showed higher oxygen consumption but failed to maintain their ATP production. Maternal undernutrition induces placental mitochondrial abnormalities. Although an increase in biogenesis and bioenergetic efficiency was noted, placental ATP level was reduced. Our data suggest that placental mitochondrial defects may be implicated in fetoplacental pathologies.

Potential Mechanism for PM 10 Effects on Birth Outcomes: In Utero Exposure Linked to Mitochondrial DNA Damage

Vol. 120, No. 9 News | Science SelectionsOpen AccessPotential Mechanism for PM10 Effects on Birth Outcomes: In Utero Exposure Linked to Mitochondrial DNA Damageis accompanied byPlacental Mitochondrial DNA Content and Particulate Air Pollution during in Utero Life Tanya Tillett Tanya Tillett Search for more papers by this author Published:1 September 2012https://doi.org/10.1289/ehp.120-a363bCited by:4View Article in:中文版AboutSectionsPDF ToolsDownload CitationsTrack Citations ShareShare onFacebookTwitterLinked InReddit A number of studies have associated exposure to particulate matter (PM) with adverse birth outcomes such as low birth weight. Much is still unknown, however, about the mechanisms that might induce these outcomes. Researchers now report an association between abnormal placental mitochondrial DNA (mtDNA) content—a marker indicative of mitochondrial dysfunction, which may be related to the development of some diseases—and fetal exposure to coarse PM (PM10) during the last trimester of pregnancy [EHP 120(9):1346–1352; Janssen et al.]. Although similar to nuclear DNA in composition and function, mtDNA has fewer protective components and less-efficient repair mechanisms, rendering it particularly vulnerable to oxidative damage.The 178 mothers in the study, who had given birth between 5 February 2010 and 3 April 2011, were part of a larger prospective initiative called ENVIRONAGE. The women were classified by age, ethnicity, smoking status, place of residence, and other demographics. Regional background levels of PM10 were calculated for each mother’s home address using satellite-based data, and the distance from each home to a major road was geocoded. Mothers’ residential PM10 exposures were calculated for the following time periods: 0–7 days before delivery, each trimester of pregnancy (1–13 weeks, 14–28 weeks, and 29 weeks to delivery), and the last month of pregnancy.Immediately after each delivery the research team collected the placenta and a sample of umbilical cord blood, which were assessed for mtDNA content. They then analyzed the relationship between mtDNA content and PM10 exposure as well as residential distance to major roads. They found that a 10-µg/m3 increase in PM10 exposure was associated with a 10.1% reduction in placental mtDNA content in the last week of pregnancy, a 16.1% reduction in the last month of pregnancy, and a 17.4% reduction in the third trimester. Living closer to a major road—an indication of higher exposure to air pollution from traffic—was also associated with lower placental mtDNA content.No statistically significant association was observed between cord blood mtDNA content and PM10 exposure during any defined time period. The researchers speculate this could reflect tissue-level differences in exposure or effects.The study is limited by the researchers’ inability to exclude the possibility of residual confounding or misclassification, but the findings suggest that prenatal PM10 exposure during the last trimester of pregnancy may cause mitochondrial dysfunction, indicating a possible window of susceptibility. Future research is needed to understand the potential health effects of decreased mtDNA content.FiguresReferencesRelatedDetailsCited by Gheissari R, Liao J, Garcia E, Pavlovic N, Gilliland F, Xiang A and Chen Z (2022) Health Outcomes in Children Associated with Prenatal and Early-Life Exposures to Air Pollution: A Narrative Review, Toxics, 10.3390/toxics10080458, 10:8, (458) Zhang H, Zhang X, Zhang H, Luo H, Feng Y, Wang J, Huang C and Yu Z (2022) Assessing the effect of fine particulate matter on adverse birth outcomes in Huai River Basin, Henan, China, 2013–2018, Environmental Pollution, 10.1016/j.envpol.2022.119357, 306, (119357), Online publication date: 1-Aug-2022. Yu Z, Zhang X, Zhang J, Feng Y, Zhang H, Wan Z, Xiao C, Zhang H, Wang Q and Huang C (2022) Gestational exposure to ambient particulate matter and preterm birth: An updated systematic review and meta-analysis, Environmental Research, 10.1016/j.envres.2022.113381, (113381), Online publication date: 1-May-2022. Mendoza-Ortega J, Reyes-Muñoz E, Nava-Salazar S, Rodríguez-Martínez S, Parra-Hernández S, Schnaas L, Suárez-Rico B, Torres-Olascoaga L, Baccarelli A, Wright R, Wright R, Estrada-Gutierrez G and Tamayo-Ortiz M (2021) Mitochondrial DNA Copy Number Adaptation as a Biological Response Derived from an Earthquake at Intrauterine Stage, International Journal of Environmental Research and Public Health, 10.3390/ijerph182211771, 18:22, (11771) Related articlesPlacental Mitochondrial DNA Content and Particulate Air Pollution during in Utero Life24 May 2012Environmental Health Perspectives Vol. 120, No. 9 September 2012Metrics About Article Metrics Publication History Originally published31 August 2012Published in print1 September 2012 Financial disclosuresPDF download License information EHP is an open-access journal published with support from the National Institute of Environmental Health Sciences, National Institutes of Health. All content is public domain unless otherwise noted. 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Placental Mitochondrial DNA Content and Particulate Air Pollution during in Utero Life

Background: Studies emphasize the importance of particulate matter (PM) in the formation of reactive oxygen species and inflammation. We hypothesized that these processes can influence mitochondrial function of the placenta and fetus.Objective: We investigated the influence of PM10 exposure during pregnancy on the mitochondrial DNA content (mtDNA content) of the placenta and umbilical cord blood.Methods: DNA was extracted from placental tissue (n = 174) and umbilical cord leukocytes (n = 176). Relative mtDNA copy numbers (i.e., mtDNA content) were determined by real-time polymerase chain reaction. Multiple regression models were used to link mtDNA content and in utero exposure to PM10 over various time windows during pregnancy.Results: In multivariate-adjusted analysis, a 10-µg/m³ increase in PM10 exposure during the last month of pregnancy was associated with a 16.1% decrease [95% confidence interval (CI): –25.2, –6.0%, p = 0.003] in placental mtDNA content. The corresponding effect size for average PM10 exposure during the third trimester was 17.4% (95% CI: –31.8, –0.1%, p = 0.05). Furthermore, we found that each doubling in residential distance to major roads was associated with an increase in placental mtDNA content of 4.0% (95% CI: 0.4, 7.8%, p = 0.03). No association was found between cord blood mtDNA content and PM10 exposure.Conclusions: Prenatal PM10 exposure was associated with placental mitochondrial alterations, which may both reflect and intensify oxidative stress production. The potential health consequences of decreased placental mtDNA content in early life must be further elucidated.