Montoya-Williams D, Quinlan J, Clukay C, Rodney N C, Kertes D A, Mulligan C J
1Department of Pediatrics,University of Florida,Gainesville,FL,USA.
2Department of Anthropology,University of Florida,Gainesville,FL,USA.
J Dev Orig Health Dis. 2018 Apr;9(2):215-222. doi: 10.1017/S2040174417000800. Epub 2017 Oct 11.
Maternal stress has been linked to low birth weight in newborns. One potential pathway involves epigenetic changes at candidate genes that may mediate the effects of prenatal maternal stress on birth weight. This relationship has been documented in stress-related genes, such as NR3C1. There is less literature exploring the effect of stress on growth-related genes. IGF1 and IGF2 have been implicated in fetal growth and development, though via different mechanisms as IGF2 is under imprinting control. In this study, we tested for associations between prenatal stress, methylation of IGF1 and IGF2, and birth weight. A total of 24 mother-newborn dyads in the Democratic Republic of Congo were enrolled. Ethnographic interviews were conducted with mothers at delivery to gather culturally relevant war-related and chronic stressors. DNA methylation data were generated from maternal venous, cord blood and placental tissue samples. Multivariate regressions were used to test for associations between stress measures, DNA methylation and birth weight in each of the three tissue types. We found an association between IGF2 methylation in maternal blood and birth weight. Previous literature on the relationship between IGF2 methylation and birth weight has focused on methylation at known differentially methylated regions in cord blood or placental samples. Our findings indicate there may be links between the maternal epigenome and low birth weight that rely on mechanisms outside known imprinting pathways. It thus may be important to consider the effect of maternal exposures and epigenetic profiles on birth weight even in the setting of maternally imprinted genes such as IGF2.
母体应激与新生儿低出生体重有关。一种潜在途径涉及候选基因的表观遗传变化，这些变化可能介导产前母体应激对出生体重的影响。这种关系已在与应激相关的基因（如NR3C1）中得到记录。探索应激对生长相关基因影响的文献较少。IGF1和IGF2与胎儿生长发育有关，尽管IGF2受印记控制，二者作用机制不同。在本研究中，我们测试了产前应激、IGF1和IGF2的甲基化与出生体重之间的关联。刚果民主共和国共有24对母婴被纳入研究。在分娩时对母亲进行人种学访谈，以收集与文化相关的战争相关和慢性应激源信息。从母体静脉血、脐带血和胎盘组织样本中获取DNA甲基化数据。使用多变量回归来测试三种组织类型中应激指标、DNA甲基化与出生体重之间的关联。我们发现母体血液中IGF2甲基化与出生体重之间存在关联。先前关于IGF2甲基化与出生体重关系的文献主要关注脐带血或胎盘样本中已知差异甲基化区域的甲基化情况。我们的研究结果表明，母体表观基因组与低出生体重之间可能存在依赖于已知印记途径之外机制的联系。因此，即使在诸如IGF2等母体印记基因的情况下，考虑母体暴露和表观遗传特征对出生体重的影响可能也很重要。
