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Sexually dimorphic DNA methylation and gene expression patterns in human first trimester placenta
Tania L Gonzalez1, Bryn E Willson1, Erica T Wang1,2
1Department of Obstetrics and Gynecology, Cedars-Sinai Medical Center, 8635 West 3rd Street, Suite 160, Los Angeles, CA, 90048, USA.
Biology of Sex Differences
|August 16, 2024
Summary
Fetal sex influences early placental development, with distinct DNA methylation patterns observed between male and female placentas in the first trimester. These epigenetic differences correlate with gene expression, potentially impacting pregnancy health.
Area of Science:
- Reproductive Biology
- Epigenetics
- Genomics
Background:
- Fetal sex and placental development are crucial for pregnancy outcomes.
- Early placental development in the first trimester is understudied.
- Understanding sex-based placental differences can inform maternal-fetal health strategies.
Purpose of the Study:
- To investigate sex-based differences in DNA methylation and gene expression in the first-trimester human placenta.
- To identify specific genes and epigenetic marks associated with fetal sex.
- To explore the correlation between DNA methylation and gene expression in early placental development.
Main Methods:
- Recruitment of pregnant subjects in late first trimester (weeks 10-14) for chorionic villus sampling.
- Isolation of DNA and RNA from placenta tissue of singleton pregnancies with normal karyotype.
- Analysis of DNA methylation using Illumina MethylationEPIC BeadChip and gene expression via RNA-sequencing.
Main Results:
- 151 differentially methylated probes (DMPs) and 152 sexually dimorphic genes were identified.
- Significant correlations found between DNA methylation and sexually dimorphic gene expression for genes like ZNF300 and CSMD1.
- Specific CpG sites and differentially methylated regions showed sex-specific methylation patterns.
Conclusions:
- Sex-dimorphic differential methylation and gene expression in the first-trimester placenta are subtle but significant.
- Epigenetic regulation via DNA methylation may contribute to sex-based differences in early placental development.
- These findings highlight potential molecular mechanisms influencing fetal-maternal health from the first trimester.
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