Gliga Anda R, Malin Igra Annachiara, Hellberg Alexander, Engström Karin, Raqib Rubhana, Rahman Anisur, Vahter Marie, Kippler Maria, Broberg Karin
Institute of Environmental Medicine, Karolinska Institutet, Box 210, 171 77 Stockholm, Sweden.
Institute of Environmental Medicine, Karolinska Institutet, Box 210, 171 77 Stockholm, Sweden.
Environ Int. 2022 May;163:107188. doi: 10.1016/j.envint.2022.107188. Epub 2022 Mar 22.
Cadmium (Cd) exposure during gestation has been associated with altered DNA methylation at birth, but it is not known if the changes in methylation persist into childhood.
To evaluate whether gestational Cd-related changes of DNA methylation persist from birth to 9 years of age.
We studied mother-child dyads in a longitudinal cohort in rural Bangladesh. Cadmium concentrations in maternal blood (erythrocyte fraction; Ery-Cd) at gestational week 14 and in child urine (U-Cd, long-term exposure marker) at 9 years were measured using inductively coupled plasma mass spectrometry. The epigenome-wide DNA methylation was measured in mononuclear cells (PBMCs) prepared from cord blood and peripheral blood at 9 years in 71 children (hereafter referred to as the explorative group) by Infinium HumanMethylation450K BeadChip. Replication of one differentially methylated region (DMR; 9 CpG sites) was performed in PBMCs of 160 9-year-old children (validation group) by EpiTyper MALDI-TOF mass spectrometry.
The median maternal Ery-Cd concentration was 1.24 µg/kg (range 0.35, 4.55) in the explorative group and 0.83 µg/kg (0.08, 2.97) in the validation group. The median U-Cd concentration in the 9-year-old children was 0.26 µg/L (0.09, 1.06) in the explorative group and 0.32 µg/L (0.07, 1.33) in the validation group. In the explorative group, we identified ten DMRs, both in cord blood and in PBMCs at 9 years, that were associated with maternal Ery-Cd. Eight out of the ten DMRs were hypomethylated and three of the hypomethylated DMRs were located in the HLA region on chromosome 6. One of the DMRs (hypomethylated) in the HLA region (upstream of the zinc finger protein 57 homolog, ZFP57 gene) was replicated in the validation group, and we found that it was hypomethylated in relation to maternal Ery-Cd, but not child U-Cd.
Gestational exposure to Cd appears to be associated with regional changes, especially hypomethylated, in DNA methylation that linger from birth up to prepubertal age.
孕期镉（Cd）暴露与出生时DNA甲基化改变有关，但尚不清楚甲基化变化是否会持续到儿童期。
评估孕期与镉相关的DNA甲基化变化从出生到9岁是否持续存在。
我们在孟加拉国农村的一个纵向队列中研究了母婴二元组。使用电感耦合等离子体质谱法测量孕14周时母血（红细胞部分；Ery-Cd）和9岁时儿童尿液（U-Cd，长期暴露标志物）中的镉浓度。通过Infinium HumanMethylation450K BeadChip对71名儿童（以下简称探索组）脐带血和9岁时外周血制备的单核细胞（PBMC）进行全基因组DNA甲基化测量。通过EpiTyper MALDI-TOF质谱法在160名9岁儿童的PBMC中对一个差异甲基化区域（DMR；9个CpG位点）进行复制（验证组）。
探索组中母血Ery-Cd浓度中位数为1.24μg/kg（范围0.35，4.55），验证组为0.83μg/kg（0.08，2.97）。9岁儿童U-Cd浓度中位数在探索组为0.26μg/L（0.09，1.06），在验证组为0.32μg/L（0.07，1.33）。在探索组中，我们在脐带血和9岁时的PBMC中均鉴定出10个与母血Ery-Cd相关的DMR。10个DMR中有8个发生低甲基化，其中3个低甲基化DMR位于6号染色体的HLA区域。HLA区域（锌指蛋白57同源物ZFP57基因上游）中的一个DMR（低甲基化）在验证组中得到复制，我们发现它与母血Ery-Cd相关呈低甲基化，但与儿童U-Cd无关。
孕期镉暴露似乎与DNA甲基化的区域变化有关，尤其是低甲基化，这种变化从出生一直持续到青春期前。
