基于性别的胎盘 DNA 甲基化谱与胎龄的关系：NIH ECHO 荟萃分析。

Sex-based differences in placental DNA methylation profiles related to gestational age: an NIH ECHO meta-analysis.

机构信息

Department of Environmental Sciences and Engineering, University of North Carolina at Chapel Hill, Chapel Hill, NC, USA.

College of Public Health, University of South Florida, Tampa, FL, USA.

出版信息

Epigenetics. 2023 Dec;18(1):2179726. doi: 10.1080/15592294.2023.2179726.

The placenta undergoes many changes throughout gestation to support the evolving needs of the foetus. There is also a growing appreciation that male and female foetuses develop differently , with unique epigenetic changes in placental tissue. Here, we report meta-analysed sex-specific associations between gestational age and placental DNA methylation from four cohorts in the National Institutes of Health (NIH) Environmental influences on Child Health Outcomes (ECHO) Programme (355 females/419 males, gestational ages 23-42 weeks). We identified 407 cytosine-guanine dinucleotides (CpGs) in females and 794 in males where placental methylation levels were associated with gestational age. After cell-type adjustment, 55 CpGs in females and 826 in males were significant. These were enriched for biological processes critical to the immune system in females and transmembrane transport in males. Our findings are distinct between the sexes: in females, associations with gestational age are largely explained by differences in placental cellular composition, whereas in males, gestational age is directly associated with numerous alterations in methylation levels.

胎盘在整个妊娠期会发生许多变化，以支持胎儿不断发展的需求。人们越来越认识到，男性和女性胎儿的发育方式不同，胎盘组织中存在独特的表观遗传变化。在这里，我们报告了美国国立卫生研究院（NIH）环境对儿童健康结果的影响（ECHO）计划中的四个队列中，与妊娠年龄相关的胎盘 DNA 甲基化的性别特异性荟萃分析结果（355 名女性/419 名男性，妊娠年龄 23-42 周）。我们在女性中鉴定出 407 个胞嘧啶-鸟嘌呤二核苷酸（CpG），在男性中鉴定出 794 个 CpG，其中胎盘甲基化水平与妊娠年龄相关。在细胞类型调整后，女性中有 55 个 CpG，男性中有 826 个 CpG 具有统计学意义。这些 CpG 在女性中富集了对免疫系统至关重要的生物学过程，在男性中富集了跨膜转运。我们的研究结果在性别之间存在明显差异：在女性中，与妊娠年龄相关的关联主要是由胎盘细胞组成的差异解释的，而在男性中，妊娠年龄与甲基化水平的许多改变直接相关。