Placental transcriptomic signatures of prenatal exposure to Hydroxy-Polycyclic aromatic hydrocarbons

Paquette, Alison G.; Lapehn, Samantha; Freije, Sophie; MacDonald, James W.; Bammler, Theo K.; Day, Drew B; Loftus, Christine T.; Kannan, Kurunthachalam; Mason, W. Alex; Bush, Nicole R.; LeWinn, Kaja Z.; Enquobahrie, Daniel A.; Marsit, Carmen J.; Sathyanarayana, Sheela

doi:10.1016/j.envint.2023.107763

Cited by 9 publications

(4 citation statements)

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“…A study of 1,677 women measured urinary PAH metabolites in the 2nd trimester and linked these to preterm birth; female fetuses were found to be more susceptible to 2-PHEN and 1-PYR exposures than the males [7]. Furthermore, a recent study reported sex-modi cation of associations between urinary OH-PAH concentrations in mid-pregnancy and the placental transcriptome, with more affected transcripts identi ed in females than males [43].…”

Section: Discussionmentioning

confidence: 99%

Urinary polycyclic aromatic hydrocarbon metabolites and their association with oxidative stress among pregnant women in Los Angeles

Meng,

Mitra,

Rosario

et al. 2024

Preprint

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Background Polycyclic aromatic hydrocarbons (PAHs) have been linked to adverse birth outcomes, but few epidemiological studies to date have evaluated associations between urinary PAH metabolites and oxidative stress biomarkers in pregnancy. Methods We measured a total of 7 PAH metabolites and 2 oxidative stress biomarkers (malondialdehyde (MDA), 8-hydroxy-2’-deoxyguanosine (8-OHdG)) in urine samples collected up to three times during pregnancy in 159 women enrolled at antenatal clinics at the University of California Los Angeles during 2016–2019. Using multiple linear regression models, we estimated the percentage change (%) and 95% confidence interval (CI) in 8-OHdG and MDA measured at each sample collection time per doubling of PAH metabolite concentrations. Results Most PAH metabolites were positively associated with both urinary oxidative stress biomarkers, MDA and 8-OHdG, with stronger associations in early and late pregnancy. Women pregnant with male fetuses exhibited slightly larger increases in both MDA and 8-OHdG in association with PAH exposures in early and late pregnancy. Conclusion Urinary OH-PAH biomarkers are associated with increases in oxidative stress during pregnancy, especially in early and late pregnancy. Sex differences in associations between PAH exposures and oxidative stress need to be further explored in the future.

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Section: Discussionmentioning

confidence: 99%

Urinary polycyclic aromatic hydrocarbon metabolites and their association with oxidative stress among pregnant women in Los Angeles

Meng,

Mitra,

Rosario

et al. 2024

Preprint

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“…Gestational exposure to PAHs may also trigger transcriptomic and epigenetic changes ( Herbstman et al, 2012 ). For example, a recent study found that maternal urinary OH-PAH metabolites were associated with changes in the placental transcriptome ( Paquette et al, 2023 ). In particular, phenanthrene metabolites showed strong associations with expression of TRIP13 and genes related to vitamin absorption/digestion, consistent with our finding of stronger adverse associations for phenanthrene metabolite 1/9-PHEN relative to other OH-PAHss.…”

Section: Discussionmentioning

confidence: 99%

“… Majewska et al (2018) found that lung function growth trajectories were lower among girls exposed prenatally to HMW PAHs, but did not differ by exposure among boys, though the interaction between child sex and exposure was not statistically significant. A recent study of maternal OH-PAHs and placental gene expression may offer a potential mechanism to explain a stronger adverse effect on airway development and function in females; relative to males, placentas from female births had over 60% more genes for which expression was associated with OH-PAH concentrations, including genes related to vitamin absorption ( Paquette et al, 2023 ). More research is needed to clarify potential effect modification by child sex and the role of specific parent compounds and metabolites.…”

Section: Discussionmentioning

confidence: 99%

Prenatal polycyclic aromatic hydrocarbon exposure and asthma at age 8-9 years in a multi-site longitudinal study

Sherris

Loftus

Szpiro

et al. 2023

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Background and aim: Studies suggest prenatal exposure to polycyclic aromatic hydrocarbons (PAHs) may influence wheezing or asthma in preschool-aged children. However, the impact of prenatal PAH exposure on asthma and wheeze in middle childhood remain unclear. We investigated these associations in diverse participants from the ECHO PATHWAYS multi-cohort consortium.Methods We included 1,081 birth parent-child dyads across five U.S. cities. Maternal urinary mono-hydroxylated PAH metabolite concentrations (OH-PAH) were measured during mid-pregnancy. Asthma at age 8–9 years and wheezing trajectory across childhood were characterized by caregiver reported asthma diagnosis and asthma/wheeze symptoms. We used logistic and multinomial regression to estimate odds ratios of asthma and childhood wheezing trajectories associated with five individual OH-PAHs, adjusting for urine specific gravity, various maternal and child characteristics, study site, prenatal and postnatal smoke exposure, and birth year and season in single metabolite and mutually adjusted models. We used multiplicative interaction terms to evaluate effect modification by child sex and explored OH-PAH mixture effects through Weighted Quantile Sum regression.Results The prevalence of asthma in the study population was 10%. We found limited evidence of adverse associations between pregnancy OH-PAH concentrations and asthma or wheezing trajectories. We observed adverse associations between 1/9-hydroxyphenanthrene and asthma and persistent wheeze among girls, and evidence of inverse associations with asthma for 1-hydroxynathpthalene, which was stronger among boys, though tests for effect modification by child sex were not statistically.Conclusions In a large, multi-site cohort, we did not find strong evidence of an association between prenatal exposure to PAHs and child asthma at age 8–9 years, though some adverse associations were observed among girls.

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“…Expression of these genes was normalized using the trimmed mean of M-values followed by conversion to log counts per million (logCPM) (33). Genes with low expression were removed by filtering for genes with an average logCPM>0 as previously described (26,34,35). Filtering by expression was conducted separately for the samples with plasma 25(OH)D measured at mid-pregnancy and plasma 25(OH)D measured at delivery.…”

Section: Differentially Expressed Gene Identificationmentioning

confidence: 99%

Associations Between Prenatal Vitamin D and Placental Gene Expression

Parenti,

Melough,

Lapehn

et al. 2024

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Background: Vitamin D is a hormone regulating gene transcription. Prenatal vitamin D has been linked to immune and vascular function in the placenta, a key organ of pregnancy. To date, studies of vitamin D and placental gene expression have focused on a limited number of candidate genes. Transcriptome-wide RNA sequencing can provide a more complete representation of the placental effects of vitamin D. Objective: We investigated the association between prenatal vitamin D levels and placental gene expression in a large, prospective pregnancy cohort. Methods: Participants were recruited in Shelby County, Tennessee in the Conditions Affecting Neurocognitive Development and Learning in Early childhood (CANDLE) study. Vitamin D level (plasma total 25-hydroxyvitatmin D, [25(OH)D]) was measured at mid-pregnancy (16-28 weeks' gestation) and delivery. Placenta samples were collected at birth. RNA was isolated and sequenced. We identified differentially expressed genes (DEGs) using adjusted linear regression models. We also conducted weighted gene co-expression network analysis (WGCNA). Results: The median 25(OH)D of participants was 21.8 ng/mL at mid-pregnancy (N=774, IQR: 15.4-26.5 ng/mL) and 23.6 ng/mL at delivery (N=753, IQR: 16.8-29.1 ng/mL). Placental expression of 25 DEGs was associated with 25(OH)D at mid-pregnancy, but no DEG was associated with 25(OH)D at delivery. DEGs were related to energy metabolism, cytoskeletal function, and RNA transcription. Using WGCNA, we identified 2 gene modules whose expression was associated with 25(OH)D at mid-pregnancy and 1 module associated with 25(OH)D at delivery. These modules were enriched for genes related to mitochondrial and cytoskeletal function, and were regulated by transcription factors includingARNT2,BHLHE40,FOSL2,JUND, andNFKB1. Conclusions: Our results indicate that 25(OH)D during mid-pregnancy, but not at delivery, is associated with placental gene expression at birth. Future research is needed to investigate a potential role of vitamin D in programming placental mitochondrial metabolism, intracellular transport, and transcriptional regulation during pregnancy.

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Placental transcriptomic signatures of prenatal exposure to Hydroxy-Polycyclic aromatic hydrocarbons

Cited by 9 publications

References 102 publications

Urinary polycyclic aromatic hydrocarbon metabolites and their association with oxidative stress among pregnant women in Los Angeles

Urinary polycyclic aromatic hydrocarbon metabolites and their association with oxidative stress among pregnant women in Los Angeles

Prenatal polycyclic aromatic hydrocarbon exposure and asthma at age 8-9 years in a multi-site longitudinal study

Associations Between Prenatal Vitamin D and Placental Gene Expression

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