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Early pregnancy dyslipidemia is associated with placental DNA methylation at loci relevant for cardiometabolic diseases.

ABSTRACT: Aim: To identify placental DNA methylation changes that are associated with early pregnancy maternal dyslipidemia. Materials & methods: We analyzed placental genome-wide DNA methylation (n = 262). Genes annotating differentially methylated CpGs were evaluated for gene expression in placenta (n = 64). Results: We found 11 novel significant differentially methylated CpGs associated with high total cholesterol, low-density lipoprotein cholesterol and triglycerides, and low high-density lipoprotein cholesterol. High triglycerides were associated with decreased methylation of cg02785814 (ALX4) and decreased expression of ALX4 in placenta. Genes annotating the differentially methylated CpGs play key roles in lipid metabolism and were enriched in dyslipidemia pathways. Functional annotation found cis-methylation quantitative trait loci for genetic loci in ALX4 and EXT2. Conclusion: Our findings lend novel insights into potential placental epigenetic mechanisms linked with maternal dyslipidemia. Trial Registration: ClinicalTrials.gov, NCT00912132.

SUBMITTER: Ouidir M

PROVIDER: S-EPMC7466909 | biostudies-literature | 2020 Jun

REPOSITORIES: biostudies-literature

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Early pregnancy dyslipidemia is associated with placental DNA methylation at loci relevant for cardiometabolic diseases.

Ouidir Marion M Zeng Xuehuo X Workalemahu Tsegaselassie T Shrestha Deepika D Grantz Katherine L KL Mendola Pauline P Zhang Cuilin C Tekola-Ayele Fasil F

Epigenomics 20200601 11

Aim: To identify placental DNA methylation changes that are associated with early pregnancy maternal dyslipidemia. Materials & methods: We analyzed placental genome-wide DNA methylation (n = 262). Genes annotating differentially methylated CpGs were evaluated for gene expression in placenta (n = 64). Results: We found 11 novel significant differentially methylated CpGs associated with high total cholesterol, low-density lipoprotein cholesterol and triglycerides, and low high ...[more]

PMID: 32677467

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Project description:Selective serotonin reuptake inhibitors (SSRIs) for treatment of prenatal maternal depression have been associated with neonatal neurobehavioral disturbances, though the molecular mechanisms remain poorly understood. In utero exposure to SSRIs may affect DNA methylation (DNAme) in the human placenta, an epigenetic mark that is established during development and is associated with gene expression. Chorionic villus samples from 64 human placentas were profiled with the Illumina MethylationEPIC BeadChip; clinical assessments of maternal mood and SSRI treatment records were collected at multiple time points during pregnancy. Case distribution was 20 SSRI-exposed cases and 44 SSRI non-exposed cases. Maternal depression was defined using a mean maternal Hamilton Depression score > 8 to indicate symptomatic depressed mood ("maternally-depressed"), and we further classified cases into SSRI-exposed, maternally-depressed (n = 14); SSRI-exposed, not maternally-depressed (n = 6); SSRI non-exposed, maternally-depressed (n = 20); and SSRI non-exposed, not maternally-depressed (n = 24). For replication, Illumina 450K DNAme profiles were obtained from 34 additional cases from an independent cohort (n = 17 SSRI-exposed, n = 17 SSRI non-exposed). No CpGs were differentially methylated at FDR < 0.05 comparing SSRI-exposed to non-exposed placentas, in a model adjusted for mean maternal Hamilton Depression score, or in a model restricted to maternally-depressed cases with and without SSRI exposure. However, at a relaxed threshold of FDR < 0.25, five CpGs were differentially methylated (|Δβ| > 0.03) by SSRI exposure status. Four were covered by the replication cohort measured by the 450K array, but none replicated. No CpGs were differentially methylated (FDR < 0.25) comparing maternally depressed to not depressed cases. In sex-stratified analyses for SSRI-exposed versus non-exposed cases (females n = 31; males n = 33), three additional CpGs in females, but none in males, were differentially methylated at the relaxed FDR < 0.25 cut-off. We did not observe large-scale alterations of DNAme in placentas exposed to maternal SSRI treatment, as compared to placentas with no SSRI exposure. We also found no evidence for altered DNAme in maternal depression-exposed versus depression non-exposed placentas. This novel work in a prospectively-recruited cohort with clinician-ascertained SSRI exposure and mood assessments would benefit from future replication.

Dataset Information

Early pregnancy dyslipidemia is associated with placental DNA methylation at loci relevant for cardiometabolic diseases.

Publications

Early pregnancy dyslipidemia is associated with placental DNA methylation at loci relevant for cardiometabolic diseases.

Similar Datasets

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