Differences in placental telomere length suggest a link between racial disparities in birth outcomes and cellular aging.
Differences in placental telomere length suggest a link between racial disparities in birth outcomes and cellular aging.
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DOI：
10.1016/j.ajog.2016.11.1027
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发表时间：
2017-03
影响因子：
9.8
通讯作者：
Drury SS
中科院分区：
文献类型：
--
作者：
Jones CW;Gambala C;Esteves KC;Wallace M;Schlesinger R;O'Quinn M;Kidd L;Theall KP;Drury SS
健康差异在生命早期就开始了，并在整个生命过程中持续存在。尽管目前的努力，黑人妇女比白人妇女表现出更大的妊娠并发症和负面围产期结局的风险。胎盘是一个复杂的多组织器官，是母亲和胎儿之间双向信息的主要换能器。胎盘功能的改变与多种不同种族的妊娠并发症有关，但对胎盘内分子因素的种族差异知之甚少。一些妊娠并发症，包括先兆子痫和胎儿生长受限，表现出种族差异，并与胎盘端粒长度较短有关，端粒长度是细胞应激和衰老的指标。细胞衰老和端粒动力学与劳动和分娩开始的分子机制有关。此外，在一系列不同的外周组织中发现了端粒长度的种族差异。总之，这些因素表明，探索胎盘端粒长度的种族差异可能为出生结果的种族差异提供新的机制见解。本研究考察了在四种不同的胎源性组织中测量的端粒长度在黑人和白人之间是否有显著差异。该研究有两个假设：(1)在不同胎盘组织类型中测量的端粒长度将是相关的；(2)在所有样本组织中端粒长度将因种族而异。在一项前瞻性研究中，从黑白单胎妊娠（N=46）的羊膜、绒毛膜、绒毛和脐带中收集胎盘组织样本。端粒长度测定采用单色多重定量实时聚合酶链反应在每个胎盘组织。还收集了人口统计和妊娠相关数据。描述性统计描述了样本的总体特征，并分别在黑人和白人妇女中进行了分析。种族的总体影响通过包含经验相关协变量的多水平混合效应线性回归模型进行评估。端粒长度在所有胎盘组织中均显著相关。胎盘组织端粒长度的两两分析显示羊膜的端粒长度明显长于绒毛膜（t= - 2.06, p=0.043）。黑人母亲胎盘样品的端粒总长度明显短于白人母亲（β= - 0.09, p=0.04）。控制相关的母婴特征加强了观察到的种族差异的显著性（β= - 0.12, p=0.02）。组织分析显示，不同种族的最大差异是绒毛膜端粒长度（t= - 2.81, p=0.007）。这些发现为胎盘端粒长度的种族差异提供了第一个证据。与白人母亲相比，来自黑人母亲的胎盘样本的端粒长度明显短。鉴于先前的研究报告端粒长度、细胞衰老和端粒动力学是导致羊膜囊破裂、分娩和分娩的分子因素，我们发现黑人母亲胎盘端粒长度较短，这表明胎盘组织细胞老化加速可能与黑人早产风险增加有关。我们的研究结果表明，胎盘细胞衰老的种族差异是健康差异的最早根源。
Health disparities begin early in life and persist across the life course. Despite current efforts Black women exhibit greater risk for pregnancy complications and negative perinatal outcomes compared to White women. The placenta, a complex multi-tissue organ, serves as the primary transducer of bidirectional information between the mother and fetus. Altered placental function is linked to multiple racially disparate pregnancy complications, however little is known about racial differences in molecular factors within the placenta. Several pregnancy complications, including preeclampsia and fetal growth restriction, exhibit racial disparities and are associated with shorter placental telomere length, an indicator of cellular stress and aging. Cellular senescence and telomere dynamics are linked to the molecular mechanisms associated with the onset of labor and parturition. Further, racial differences in telomere length are found in a range of different peripheral tissues. Together these factors suggest that exploration of racial differences in telomere length of the placenta may provide novel mechanistic insight into racial disparities in birth outcomes. This study examined whether telomere length measured in four distinct fetally-derived tissues were significantly different between Blacks and Whites. The study had two hypotheses: (1) that telomere length measured in different placental tissue types would be correlated and (2) that across all sampled tissues telomere length would differ by race. In a prospective study, placental tissue samples were collected from the amnion, chorion, villus, and umbilical cord from Black and White singleton pregnancies (N=46). Telomere length was determined using monochrome multiplex quantitative real-time polymerase chain reaction in each placental tissue. Demographic and pregnancy-related data were also collected. Descriptive statistics characterized the sample overall and among Black and White women separately. The overall impact of race was assessed by multilevel mixed-effects linear regression models that included empirically relevant covariates. Telomere length was significantly correlated across all placental tissues. Pairwise analyses of placental tissue telomere length revealed significantly longer telomere length in the amnion compared to the chorion (t=−2.06, p=0.043). Overall telomere length measured in placenta samples from Black mothers were significantly shorter than those from White mothers (β=−0.09, p=0.04). Controlling for relevant maternal and infant characteristics strengthened the significance of the observed racial differences (β=−0.12, p=0.02). Within tissue analyses revealed that the greatest difference by race was found in chorionic telomere length (t=−2.81, p=0.007). These findings provide the first evidence of racial differences in placental telomere length. Telomere length was significantly shorter in placental samples derived from Black mothers compared to White. Given previous studies reporting that telomere length, cellular senescence, and telomere dynamics are molecular factors contributing to the rupture of the amniotic sac, onset of labor, and parturition, our findings of shorter telomere length in placentas from Black mothers suggests that accelerated cellular aging across placental tissues may be relevant to the increased risk of preterm delivery in Blacks. Our results suggest that racial differences in cellular aging in the placenta contribute to the earliest roots of health disparities.