Gene expression profiles in placenta and their association with anesthesia, delivery mode and maternal diabetes

IF 3 2区医学 Q2 DEVELOPMENTAL BIOLOGY

Placenta Pub Date : 2024-10-15 DOI:10.1016/j.placenta.2024.10.008

Bassam Aljani , Annette I. Garbe , Eva-Maria Sedlmeier , Ramona Lickert , Fabian Rost , Anette-Gabriele Ziegler , Ezio Bonifacio , Anne Eugster

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引用次数: 0

Abstract

Introduction

Fetal development is dependent on placenta and affected by multiple factors including maternal diabetes. Here we aimed to identify maternal diabetes-associated changes in placentas and analyzed placental gene expression to understand its modulation by maternal diabetes and birth mode.

Methods

Placental RNAseq transcriptome analyses were performed on maternally-derived decidua and fetal-derived villous tissue from pregnancies of mothers with type 1 diabetes (n = 14), gestational diabetes (n = 6) and without diabetes (n = 14). Information on delivery mode and anesthesia were included as covariables. Analyses were performed separately for decidua and fetal tissues and adjusted for sex.

Results

Substantial placenta gene expression variation was associated with factors other than maternal diabetes, including site, sex, anesthesia type and delivery mode. Two dominant gene expression clusters aligned to anesthesia and delivery mode were observed for decidua and villous tissue. Upregulation of genes within pathways related to organ morphogenesis and downregulation of immune response to steroid- and hypoxia pathway genes was characteristic of placentas from primary cesarean section deliveries with spinal anesthesia. Opposite profiles were observed for placentas from secondary cesarean and epidural anesthesia deliveries. Placentas from vaginal delivery had intermediate gene expression profiles. More subtle changes were associated with maternal diabetes: upregulation of ribosome activity, down-regulation of maternally-derived decidua chemokine signaling pathways and for gestational diabetes, alteration in hypoxia response genes.

Discussion

The findings reveal suppression of immune pathways and upregulation of ribosome activity in the placenta by maternal diabetes highlighting the importance of confounding factors when examining cell and tissue expression profiles. Further studies should determine whether the observed gene expression differences are related to underlying causes for cesarean section deliveries.

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胎盘中的基因表达谱及其与麻醉、分娩方式和产妇糖尿病的关系。

引言胎儿的发育依赖于胎盘，并受到包括母体糖尿病在内的多种因素的影响。在此，我们旨在确定胎盘中与母体糖尿病相关的变化，并分析胎盘基因表达，以了解其受母体糖尿病和分娩方式的影响：方法：对1型糖尿病（14例）、妊娠糖尿病（6例）和无糖尿病（14例）母亲的胎盘蜕膜和胎儿绒毛组织进行胎盘RNAseq转录组分析。分娩方式和麻醉信息被列为协变量。对蜕膜和胎儿组织分别进行分析，并根据性别进行调整：结果：胎盘基因表达的大量变化与产妇糖尿病以外的因素有关，包括部位、性别、麻醉类型和分娩方式。在蜕膜和绒毛组织中观察到与麻醉和分娩方式相关的两个优势基因表达群。与器官形态发生相关的通路基因上调，而对类固醇和缺氧通路基因的免疫反应下调是脊髓麻醉下初次剖宫产胎盘的特征。而二次剖宫产和硬膜外麻醉分娩的胎盘则呈现出相反的特征。阴道分娩胎盘的基因表达谱介于两者之间。更微妙的变化与孕产妇糖尿病有关：核糖体活性上调，母源性蜕膜趋化因子信号通路下调，妊娠糖尿病则与缺氧反应基因的改变有关：讨论：研究结果表明，母体糖尿病会抑制胎盘中的免疫通路并上调核糖体活性，这凸显了在研究细胞和组织表达谱时混杂因素的重要性。进一步的研究应确定观察到的基因表达差异是否与剖宫产的潜在原因有关。

本文章由计算机程序翻译，如有差异，请以英文原文为准。

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来源期刊

Placenta 医学-发育生物学

CiteScore

6.30

自引率

10.50%

发文量

391

审稿时长

78 days

期刊介绍： Placenta publishes high-quality original articles and invited topical reviews on all aspects of human and animal placentation, and the interactions between the mother, the placenta and fetal development. Topics covered include evolution, development, genetics and epigenetics, stem cells, metabolism, transport, immunology, pathology, pharmacology, cell and molecular biology, and developmental programming. The Editors welcome studies on implantation and the endometrium, comparative placentation, the uterine and umbilical circulations, the relationship between fetal and placental development, clinical aspects of altered placental development or function, the placental membranes, the influence of paternal factors on placental development or function, and the assessment of biomarkers of placental disorders.