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单绒毛膜性双胎中选择性胎儿生长受限:胎盘全转录组分析的见解。

Monochorionic twins with selective fetal growth restriction: insight from placental whole-transcriptome analysis.

机构信息

Department of Obstetrics and Gynaecology, Faculty of Medicine, the Chinese University of Hong Kong, Shatin, Hong Kong.

School of Life Sciences, the Chinese University of Hong Kong, Shatin, Hong Kong; Hong Kong Bioinformatics Centre, the Chinese University of Hong Kong, Shatin, Hong Kong.

出版信息

Am J Obstet Gynecol. 2020 Nov;223(5):749.e1-749.e16. doi: 10.1016/j.ajog.2020.05.008. Epub 2020 May 11.

DOI:10.1016/j.ajog.2020.05.008
PMID:32437666
Abstract

BACKGROUND

The underlying pathomechanism in placenta-related selective fetal growth restriction in monochorionic diamniotic twin pregnancy is not known.

OBJECTIVE

This study aimed to investigate any differences in placental transcriptomic profile between the selectively growth-restricted twins and the normally grown cotwins in monochorionic diamniotic twin pregnancies.

STUDY DESIGN

This was a prospective study of monochorionic diamniotic twin pregnancies complicated by selective fetal growth restriction. Placental biopsy specimens were obtained from the subjects in the delivery suite. The placental transcriptome of the selectively growth-restricted twin was compared with that of the normally grown cotwin. This study was divided into 2 stages: (1) gene discovery phase in which placental tissues from 5 monochorionic diamniotic twin pregnancies complicated by selective fetal growth restriction plus 2 control twin pregnancies underwent transcriptome profiling, and transcriptome profiling was carried out using whole-genome RNA sequencing; and (2) validation phase in which placental tissues from 13 monochorionic diamniotic twin pregnancies with selective fetal growth restriction underwent RNA and protein validation. RNA and protein expression levels of candidate genes were determined using quantitative real-time polymerase chain reaction and immunohistochemistry staining.

RESULTS

A total of 1429 transcripts were differentially expressed in the placentae of selectively growth-restricted twin pairs, where 610 were up-regulated and 819 were down-regulated. Endoplasmic reticulum lectin and mannose 6-phosphate receptor were consistently differentially up-regulated in all placentae of selectively growth-restricted twins. Quantitative real-time polymerase chain reaction and immunohistochemistry staining were used to validate the results (P<.05).

CONCLUSION

The expression of endoplasmic reticulum lectin and mannose 6-phosphate receptor, which are important for angiogenesis and fetal growth, was significantly increased in the placentae of selectively growth-restricted twin of a monochorionic twin pair.

摘要

背景

在单绒毛膜双羊膜囊双胎妊娠中,胎盘相关性选择性胎儿生长受限的潜在发病机制尚不清楚。

目的

本研究旨在探讨单绒毛膜双羊膜囊双胎妊娠中选择性胎儿生长受限的双胎胎盘转录组谱是否存在差异。

研究设计

这是一项前瞻性研究,纳入了伴有选择性胎儿生长受限的单绒毛膜双羊膜囊双胎妊娠。在分娩室获取研究对象的胎盘活检标本。将选择性生长受限的胎儿胎盘转录组与正常生长的胎儿胎盘转录组进行比较。本研究分为 2 个阶段:(1)基因发现阶段,对 5 例伴有选择性胎儿生长受限的单绒毛膜双羊膜囊双胎妊娠及 2 例对照双胎妊娠的胎盘组织进行转录组谱分析,采用全基因组 RNA 测序进行转录组谱分析;(2)验证阶段,对 13 例伴有选择性胎儿生长受限的单绒毛膜双羊膜囊双胎妊娠的胎盘组织进行 RNA 和蛋白质验证。采用实时定量聚合酶链反应和免疫组织化学染色法检测候选基因的 RNA 和蛋白质表达水平。

结果

在选择性生长受限的胎儿胎盘对中,共有 1429 个转录本差异表达,其中 610 个上调,819 个下调。内质网凝集素和甘露糖 6-磷酸受体在所有选择性生长受限胎儿的胎盘组织中均一致上调。实时定量聚合酶链反应和免疫组织化学染色验证了这些结果(P<.05)。

结论

内质网凝集素和甘露糖 6-磷酸受体的表达在单绒毛膜双羊膜囊双胎妊娠的选择性生长受限胎儿胎盘组织中显著增加,这对于血管生成和胎儿生长很重要。

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