孕期暴露于外源性雌激素混合物与人类胎盘全基因组DNA甲基化
Prenatal exposure to mixtures of xenoestrogens and genome-wide DNA methylation in human placenta.
作者信息
Vilahur Nadia, Bustamante Mariona, Morales Eva, Motta Valeria, Fernandez Mariana Fátima, Salas Lucas Andrés, Escaramis Georgia, Ballester Ferran, Murcia Mario, Tardon Adonina, Riaño Isolina, Santa-Marina Loreto, Ibarluzea Jesús, Arrebola Juan Pedro, Estivill Xavier, Bollati Valentina, Sunyer Jordi, Olea Nicolás
机构信息
ISGlobal, Center for Research in Environmental Epidemiology (CREAL), Barcelona, Spain.
Universitat Pompeu Fabra (UPF), Barcelona, Spain.
出版信息
Epigenomics. 2016 Jan;8(1):43-54. doi: 10.2217/epi.15.91. Epub 2015 Dec 18.
BACKGROUND
In utero exposure to xenostrogens may modify the epigenome. We explored the association of prenatal exposure to mixtures of xenoestrogens and genome-wide placental DNA methylation.
MATERIALS & METHODS: Sex-specific associations between methylation changes in placental DNA by doubling the concentration of TEXB-alpha exposure were evaluated by robust multiple linear regression. Two CpG sites were selected for validation and replication in additional male born placentas.
RESULTS
No significant associations were found, although the top significant CpGs in boys were located in the LRPAP1, HAGH, PPARGC1B, KCNQ1 and KCNQ1DN genes, previously associated to birth weight, Type 2 diabetes, obesity or steroid hormone signaling. Neither technical validation nor biological replication of the results was found in boys for LRPAP and PPARGC1B.
CONCLUSION
Some suggestive genes were differentially methylated in boys in relation to prenatal xenoestrogen exposure, but our initial findings could not be validated or replicated.
背景
子宫内暴露于外源性雌激素可能会改变表观基因组。我们探讨了产前暴露于外源性雌激素混合物与全基因组胎盘DNA甲基化之间的关联。
材料与方法
通过稳健的多元线性回归评估将TEXB-α暴露浓度加倍时胎盘DNA甲基化变化的性别特异性关联。选择两个CpG位点在另外的男性出生胎盘样本中进行验证和重复研究。
结果
未发现显著关联，尽管男孩中最显著的CpG位点位于LRPAP1、HAGH、PPARGC1B、KCNQ1和KCNQ1DN基因中，这些基因先前与出生体重、2型糖尿病、肥胖或类固醇激素信号传导有关。在男孩中未发现LRPAP和PPARGC1B结果的技术验证或生物学重复。
结论
一些提示性基因在男孩中与产前外源性雌激素暴露相关的甲基化存在差异，但我们的初步发现无法得到验证或重复。
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