Lambertini L, Li Q, Ma Y, Zhang W, Hao K, Marsit C, Chen J, Nomura Y
Department of Environmental Medicine and Public Health, Icahn School of Medicine at Mount Sinai, New York, NY, USA.
Department of Obstetrics, Gynecology and Reproductive Science, Icahn School of Medicine at Mount Sinai, New York, NY, USA.
J Dev Orig Health Dis. 2019 Apr;10(2):196-205. doi: 10.1017/S2040174418000545. Epub 2019 Apr 10.
Imprinted genes uniquely drive and support fetoplacental growth by controlling the allocation of maternal resources to the fetus and affecting the newborn's growth. We previously showed that alterations of the placental imprinted gene expression are associated with suboptimal perinatal growth and respond to environmental stimuli including socio-economic determinants. At the same time, maternal psychosocial stress during pregnancy (MPSP) has been shown to affect fetal growth. Here, we set out to test the hypothesis that placental imprinted gene expression mediates the effects of MPSP on fetal growth in a well-characterized birth cohort, the Stress in Pregnancy (SIP) Study. We observed that mothers experiencing high MPSP deliver infants with lower birthweight (P=0.047). Among the 109 imprinted genes tested, we detected panels of placental imprinted gene expression of 23 imprinted genes associated with MPSP and 26 with birthweight. Among these genes, five imprinted genes (CPXM2, glucosidase alpha acid (GAA), GPR1, SH3 and multiple ankyrin repeat domains 2 (SHANK2) and THSD7A) were common to the two panels. In multivariate analyses, controlling for maternal age and education and gestational age at birth and infant gender, two genes, GAA and SHANK2, each showed a 22% mediation of MPSP on fetal growth. These data provide new insights into the role that imprinted genes play in translating the maternal stress message into a fetoplacental growth pattern.
印记基因通过控制母体资源向胎儿的分配以及影响新生儿的生长，独特地驱动和支持胎儿-胎盘的生长。我们之前表明，胎盘印记基因表达的改变与围产期生长欠佳相关，并且对包括社会经济决定因素在内的环境刺激有反应。与此同时，孕期母亲的心理社会压力（MPSP）已被证明会影响胎儿生长。在此，我们着手在一个特征明确的出生队列——孕期压力（SIP）研究中，检验胎盘印记基因表达介导MPSP对胎儿生长影响的假说。我们观察到，经历高MPSP的母亲所分娩的婴儿出生体重较低（P = 0.047）。在检测的109个印记基因中，我们检测到与MPSP相关的23个印记基因以及与出生体重相关的26个印记基因的胎盘印记基因表达谱。在这些基因中，有5个印记基因（CPXM2、α-酸性葡萄糖苷酶（GAA）、GPR1、含SH3结构域和多个锚蛋白重复结构域2（SHANK2）以及THSD7A）在这两个谱中是共有的。在多变量分析中，在控制了母亲年龄、教育程度、出生时的孕周和婴儿性别后，两个基因，GAA和SHANK2，各自显示出MPSP对胎儿生长有22%的中介作用。这些数据为印记基因在将母体压力信息转化为胎儿-胎盘生长模式中所起的作用提供了新的见解。
