Prenatal stress and newborn telomere length
Prenatal stress and newborn telomere length
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DOI：
10.1016/j.ajog.2016.01.177
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发表时间：
2016-07-01
影响因子：
9.8
通讯作者：
Haussmann, Mark F.
中科院分区：
文献类型：
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作者：
Marchetto, Nicole M.;Glynn, Rebecca A.;Haussmann, Mark F.
背景：健康与疾病假说的发展起源是基于这样一个前提，即许多慢性疾病的根源在于胎儿的发育。具体地说，怀孕期间的母亲压力与胎儿发育改变和许多不利的长期健康后果有关。虽然这种作用的机制目前还不清楚，但在细胞水平上，可能的中介是端粒长度的调节。端粒动力学似乎在疾病进展中起作用，不利的宫内环境可能有助于新生儿建立短端粒。根据这一点，最近有报道称，产前应激与新生儿平均端粒长度的缩短显著相关。然而，这一发现尚未被重复，目前我们还不知道端粒长度分布中不同大小类别的端粒是否会受到产前应激的不同影响。检查端粒长度频率分布很重要，因为分布中最短的端粒似乎是最能指示端粒功能障碍的指标，因此也是人类死亡率和发病率的最佳预测因子。目的：我们调查了整个妊娠过程中母亲应激对新生儿平均端粒长度和端粒长度频率分布的影响。研究设计：我们在一家城市教学医院对24名母亲-新生儿进行了前瞻性队列研究。非异常、无并发症妊娠的孕妇在妊娠晚期被招募和评估。使用Holmes和Rahe应激量表对母亲的心理社会压力进行量化，并将其归类为高压力(>；=300分)或低压力(>；=299分)暴露。结果：母体应激与新生儿端粒长度呈显著负相关(β=-0.463，P=0.0 4)。母亲孕期承受高压力的新生儿端粒长度(6.98+/-0.41kb)明显短于低压力母亲的新生儿(8.74+/-0.24kb；t=-3.99，P=0.003)。此外，高压力和低压力母亲之间新生儿端粒长度的差异是由于端粒长度分布的变化，高应激组表现出较长端粒的不足和较短端粒的过度表达。结论：我们的发现重复了最近的其他研究，并首次表明，产前应激导致新生儿平均端粒长度的差异是由于整体端粒分布的变化。
BACKGROUND: The developmental origin of the health and disease hypothesis is based on the premise that many chronic diseases have their roots in fetal development. Specifically, maternal stress during pregnancy is associated with altered fetal development and many adverse long-term health outcomes. Although the mechanisms underlying this effect are currently unclear, at the cellular level 1 possible mediator is the regulation of telomere length. Telomere dynamics appear to play a role in disease progression, and an adverse intrauterine environment may contribute in the establishment of short telomeres in newborns. In accordance with this, it was recently reported that prenatal stress is significantly associated with shorter mean newborn telomere length. However, this finding has yet to be replicated, and currently we know nothing about whether different size classes of telomeres within the telomere length distribution are differentially affected by prenatal stress. Examining telomere length frequency distributions is important, because the shortest telomeres in the distribution appear to be the most indicative of telomere dysfunction and thus the best predictors of mortality and morbidity in humans.OBJECTIVE: We investigated the effects of intrauterine exposure to maternal stress over the whole course of gestation on newborn mean telomere length and telomere length frequency distributions.STUDY DESIGN: We conducted a prospective cohort study of 24 mother-newborn dyads at an urban teaching hospital. Pregnant women with nonanomalous, uncomplicated pregnancies were recruited and assessed in the third trimester of gestation. Maternal psychosocial stress was quantified using the Holmes and Rahe Stress Scale and categorized as high stress (>= 300 points) or low stress (>= 299 points) exposure. Newborn telomere length was measured from cord blood at delivery using the Telomere Restriction Fragment assay.RESULTS: We found a significant negative association between maternal stress and newborn telomere length (beta = -0.463, P = 0.04). Newborns whose mothers experienced a high level of stress during pregnancy had significantly shorter telomere length (6.98 +/- 0.41 kb) compared to newborns of mothers with low stress (8.74 +/- 0.24 kb; t = -3.99, P = .003). Moreover, the difference in newborn telomere length between high-stress and low-stress mothers was due to a shift in the telomere length distribution, with the high-stress group showing an underrepresentation of longer telomeres and an over-representation of shorter telomeres.CONCLUSION: Our findings replicate those of other recent studies and also show, for the first time, that the prenatal stress - associated difference in newborn mean telomere length is due to a shift in the overall telomere distribution.