Kristjansson Dana, Lee Yunsung, Page Christian M, Gjessing Håkon, Magnus Maria C, Jugessur Astanand, Lyle Robert, Håberg Siri E
Center for Fertility and Health, Norwegian Institute of Public Health, Skøyen, Postboks 222, 0213, Oslo, Norway.
Department of Genetics and Bioinformatics, Norwegian Institute of Public Health, Oslo, Norway.
Sci Rep. 2024 Oct 2;14(1):22904. doi: 10.1038/s41598-024-73845-3.
Previous studies have shown cord-blood DNA methylation differences in newborns conceived using assisted reproductive technologies (ART) compared to those conceived naturally. However, whether these ART-related DNA methylation differences vary with children's sex is unknown. We hypothesize that the DNA methylation differences in cord blood between ART-conceived and naturally conceived newborns also varies by the sex of the child, with distinct patterns of differential methylation present in males and females. We investigated sex differences in cord-blood DNA methylation variation according to conception by ART using the Illumina MethylationEPIC platform, comparing 456 ART-conceived versus 507 naturally-conceived girls, and 503 ART-conceived and 473 naturally-conceived boys. We identified 37 differentially methylated CpGs according to ART-conception among girls, and 70 differentially methylated CpGs according to ART-conception among boys, when we used a 1% false discovery rate to account for multiple testing. Ten CpGs were differentially methylated according to conception by ART in both sexes. Among the genes that were associated with these CpGs, we found the BRCA1; NBR2 gene (two CpGs) was hypermethylated in girls while the APC2 (two CpGs) and NECAB3;ACTL10, (four CpGs) related to cellular signaling were hypomethylated in boys. These findings confirm the presence of sex-specific epigenetic differences, illustrating the nuanced impact of ART on the fetal epigenome. There is a need for further explorations into the implications for sex-specific developmental trajectories and health outcomes in ART-conceived children.
先前的研究表明，与自然受孕的新生儿相比，使用辅助生殖技术（ART）受孕的新生儿脐带血DNA甲基化存在差异。然而，这些与ART相关的DNA甲基化差异是否因儿童性别而异尚不清楚。我们假设，ART受孕和自然受孕的新生儿脐带血中的DNA甲基化差异也因儿童性别而异，男性和女性存在不同的差异甲基化模式。我们使用Illumina MethylationEPIC平台，研究了ART受孕情况下脐带血DNA甲基化变异的性别差异，比较了456名ART受孕女孩与507名自然受孕女孩，以及503名ART受孕男孩与473名自然受孕男孩。当我们使用1%的错误发现率来校正多重检验时，在女孩中我们鉴定出37个根据ART受孕而差异甲基化的CpG，在男孩中鉴定出70个根据ART受孕而差异甲基化的CpG。有10个CpG在两性中根据ART受孕均存在差异甲基化。在与这些CpG相关的基因中，我们发现BRCA1;NBR2基因（两个CpG）在女孩中高甲基化，而与细胞信号传导相关的APC2（两个CpG）和NECAB3;ACTL10（四个CpG）在男孩中低甲基化。这些发现证实了性别特异性表观遗传差异的存在，说明了ART对胎儿表观基因组的细微影响。有必要进一步探索ART受孕儿童性别特异性发育轨迹和健康结果的影响。
