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白细胞端粒动力学在正常妊娠过程中的变化及其与应激的关系。

Leukocyte telomere dynamics across gestation in uncomplicated pregnancies and associations with stress.

机构信息

Department of Obstetrics and Gynecology, Stanford University, 453 Quarry Road, Palo Alto, CA, 94304, USA.

Department of Pediatrics, Stanford University, Stanford, CA, USA.

出版信息

BMC Pregnancy Childbirth. 2022 May 2;22(1):381. doi: 10.1186/s12884-022-04693-0.

DOI:10.1186/s12884-022-04693-0
PMID:35501726
原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC9063069/
Abstract

BACKGROUND

Short leukocyte telomere length is a biomarker associated with stress and morbidity in non-pregnant adults. Little is known, however, about maternal telomere dynamics in pregnancy. To address this, we examined changes in maternal leukocyte telomere length (LTL) during uncomplicated pregnancies and explored correlations with perceived stress.

METHODS

In this pilot study, maternal LTL was measured in blood collected from nulliparas who delivered live, term, singleton infants between 2012 and 2018 at a single institution. Participants were excluded if they had diabetes or hypertensive disease. Samples were collected over the course of pregnancy and divided into three time periods: < 20 weeks (Timepoint 1); 20 to 36 weeks (Timepoint 2); and 37 to 9-weeks postpartum (Timepoint 3). All participants also completed a survey assessing a multivariate profile of perceived stress at the time of enrollment in the first trimester. LTL was measured using quantitative polymerase chain reaction (PCR). Wilcoxon signed-rank tests were used to compare LTL differences within participants across all timepoint intervals. To determine whether mode of delivery affected LTL, we compared postpartum Timepoint 3 LTLs between participants who had vaginal versus cesarean birth. Secondarily, we evaluated the association of the assessed multivariate stress profile and LTL using machine learning analysis.

RESULTS

A total of 115 samples from 46 patients were analyzed. LTL (mean ± SD), expressed as telomere to single copy gene (T/S) ratios, were: 1.15 ± 0.26, 1.13 ± 0.23, and 1.07 ± 0.21 for Timepoints 1, 2, and 3, respectively. There were no significant differences in LTL between Timepoints 1 and 2 (LTL T/S change - 0.03 ± 0.26, p = 0.39); 2 and 3 (- 0.07 ± 0.29, p = 0.38) or Timepoints 1 and 3 (- 0.07 ± 0.21, p = 0.06). Participants who underwent cesareans had significantly shorter postpartum LTLs than those who delivered vaginally (T/S ratio: 0.94 ± 0.12 cesarean versus 1.12 ± 0.21 vaginal, p = 0.01). In secondary analysis, poor sleep quality was the main stress construct associated with shorter Timepoint 1 LTLs (p = 0.02) and shorter mean LTLs (p = 0.03).

CONCLUSIONS

In this cohort of healthy pregnancies, maternal LTLs did not significantly change across gestation and postpartum LTLs were shorter after cesarean than after vaginal birth. Significant associations between sleep quality and short LTLs warrant further investigation.

摘要

背景

短的白细胞端粒长度是与非怀孕成年人的压力和发病相关的生物标志物。然而,关于怀孕期间母体端粒动力学的知识却很少。为了解决这个问题,我们研究了在没有并发症的妊娠过程中母体白细胞端粒长度(LTL)的变化,并探讨了与感知压力的相关性。

方法

在这项初步研究中,我们测量了 2012 年至 2018 年期间在一家机构分娩活产、足月、单胎婴儿的初产妇的血液中的母体 LTL。如果参与者患有糖尿病或高血压疾病,则将其排除在外。样本在妊娠过程中收集,并分为三个时间段:<20 周(时间点 1);20 至 36 周(时间点 2);和 37 至 9 周产后(时间点 3)。所有参与者还在第一次妊娠的第一孕期完成了一项评估感知压力的多变量概况的调查。使用定量聚合酶链反应(PCR)测量 LTL。Wilcoxon 符号秩检验用于比较所有时间点间隔内参与者的 LTL 差异。为了确定分娩方式是否会影响 LTL,我们比较了阴道分娩和剖宫产分娩的产后时间点 3 的 LTL。其次,我们使用机器学习分析评估了评估的多变量压力概况和 LTL 的关联。

结果

对 46 名患者的 115 个样本进行了分析。LTL(平均值±标准差),表示为端粒到单拷贝基因(T/S)比值,分别为:1.15±0.26、1.13±0.23 和 1.07±0.21,用于时间点 1、2 和 3。时间点 1 和 2(LTL T/S 变化-0.03±0.26,p=0.39)之间、2 和 3(-0.07±0.29,p=0.38)之间以及时间点 1 和 3(-0.07±0.21,p=0.06)之间的 LTL 无显着差异。行剖宫产的参与者的产后 LTL 明显短于阴道分娩的参与者(T/S 比值:0.94±0.12 剖宫产与 1.12±0.21 阴道,p=0.01)。在二次分析中,睡眠质量差是与时间点 1 的较短 LTL 相关的主要压力结构(p=0.02)和较短的平均 LTL 相关(p=0.03)。

结论

在本队列的健康妊娠中,母体 LTL 在妊娠期间没有显着变化,并且剖宫产后的产后 LTL 比阴道分娩后的 LTL 短。睡眠质量与短 LTL 之间的显著关联需要进一步研究。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/4b93/9063069/fa7de197c937/12884_2022_4693_Fig5_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/4b93/9063069/90f951ee7a5f/12884_2022_4693_Fig1_HTML.jpg
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