Department of Pharmacology, Dartmouth Medical School, Hanover, New Hampshire, United States of America.
PLoS One. 2012;7(3):e33794. doi: 10.1371/journal.pone.0033794. Epub 2012 Mar 14.
There is growing evidence that the intrauterine environment can impact the neurodevelopment of the fetus through alterations in the functional epigenome of the placenta. In the placenta, the HSD11B2 gene encoding the 11-beta hydroxysteroid dehydrogenase enzyme, which is responsible for the inactivation of maternal cortisol, is regulated by DNA methylation, and has been shown to be susceptible to stressors from the maternal environment.
METHODOLOGY/PRINCIPAL FINDINGS: We examined the association between DNA methylation of the HSD11B2 promoter region in the placenta of 185 healthy newborn infants and infant and maternal characteristics, as well as the association between this epigenetic variability and newborn neurobehavioral outcome assessed with the NICU Network Neurobehavioral Scales. Controlling for confounders, HSD11B2 methylation extent is greatest in infants with the lowest birthweights (P = 0.04), and this increasing methylation was associated with reduced scores of quality of movement (P = 0.04).
CONCLUSIONS/SIGNIFICANCE: These results suggest that factors in the intrauterine environment which contribute to birth outcome may be associated with placental methylation of the HSD11B2 gene and that this epigenetic alteration is in turn associated with a prospectively predictive early neurobehavioral outcome, suggesting in some part a mechanism for the developmental origins of infant neurological health.
越来越多的证据表明，宫内环境可以通过改变胎盘的功能性表观基因组来影响胎儿的神经发育。在胎盘组织中，HSD11B2 基因编码 11-β羟类固醇脱氢酶，该酶负责使母体皮质醇失活，其表达受 DNA 甲基化调控，并且易受母体环境应激源的影响。
方法/主要发现：我们研究了 185 名健康新生儿胎盘组织中 HSD11B2 启动子区域的 DNA 甲基化与婴儿和产妇特征之间的关系，以及这种表观遗传变异性与使用新生儿重症监护病房网络神经行为量表评估的新生儿神经行为结果之间的关系。在控制混杂因素后，出生体重最低的婴儿的 HSD11B2 甲基化程度最大（P=0.04），这种甲基化程度的增加与运动质量评分降低有关（P=0.04）。
结论/意义：这些结果表明，导致出生结局的宫内环境因素可能与 HSD11B2 基因的胎盘甲基化有关，而这种表观遗传改变又与前瞻性预测的早期神经行为结果相关，这在一定程度上表明了婴儿神经健康的发育起源的机制。
