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宫内生长受限对人类胎盘的影响导致性别特异性表观遗传基因激活谱存在差异调节。

Sex-specific epigenetic gene activation profiles are differentially modulated in human placentas affected by intrauterine growth restriction.

机构信息

LMU Munich, Department of Gynecology and Obstetrics, Maistrasse 11, 80337, Munich, Germany.

LMU Munich, Department of Pathology, Thalkirchner Str. 36, 80337 Munich, Germany.

出版信息

J Reprod Immunol. 2020 Jun;139:103124. doi: 10.1016/j.jri.2020.103124. Epub 2020 Mar 25.

Abstract

BACKGROUND

The purpose of this study was to investigate the sex specific expression of histone protein modifications responsible for rapid gene expression in IUGR placentas.

PATIENTS AND METHODS

We screened for fetal sex-specific expression of the histone proteins H3K4me3 and H3K9ac in 23 IUGR and 40 control placentas via immunohistochemistry. The trophoblast-like cell line BeWo was used in order to analyze a potential effect of stimulation with prednisolone on H3K4me3 and H3K9ac in vitro. Calculating regression models with additional adjustment for potential confounders were used.

RESULTS

A significantly decreased level of H3K4me3 was detectable in female syncytiotrophoblasts, whereas H3K9ac was reduced predominantly in male extravillous throphoblast (EVT). No association to the gestational age existed.

CONCLUSION

Our data showed a reduced expression of the histone proteins H3K4me3 (female) and H3K9ac (male) in IUGR, furthermore elevated cortisol levels may lead to a sex-specific down-regulation of histone proteins in IUGR placentas.

摘要

背景

本研究旨在探讨导致 IUGR 胎盘快速基因表达的组蛋白修饰的性别特异性表达。

患者和方法

我们通过免疫组织化学法筛选了 23 例 IUGR 和 40 例对照胎盘组织中组蛋白 H3K4me3 和 H3K9ac 的胎儿性别特异性表达。我们使用滋养细胞样细胞系 BeWo 来分析体外泼尼松龙刺激对 H3K4me3 和 H3K9ac 的潜在影响。使用回归模型计算,同时对潜在混杂因素进行了额外调整。

结果

在女性合体滋养细胞中可检测到 H3K4me3 的水平显著降低,而 H3K9ac 主要减少在男性绒毛外滋养细胞(EVT)中。与胎龄无相关性。

结论

我们的数据显示,IUGR 中组蛋白 H3K4me3(女性)和 H3K9ac(男性)的表达降低,此外,皮质醇水平升高可能导致 IUGR 胎盘组织中组蛋白蛋白的性别特异性下调。

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