Feto-placental and coronary endothelial genes implicated in miscarriage, congenital heart disease and stillbirth, a systematic review and meta-analysis.

Autor: Kalisch-Smith JI; Institute for Developmental and Regenerative Medicine, Department of Physiology, Anatomy and Genetics, University of Oxford, Oxford, OX3 7TY, UK. Electronic address: jacinta.kalisch-smith@idrm.ox.ac.uk., Ehtisham-Uddin N; Institute for Developmental and Regenerative Medicine, Department of Physiology, Anatomy and Genetics, University of Oxford, Oxford, OX3 7TY, UK., Rodriguez-Caro H; Institute for Developmental and Regenerative Medicine, Department of Physiology, Anatomy and Genetics, University of Oxford, Oxford, OX3 7TY, UK; Department of Oncology, University of Lausanne and Ludwig Institute for Cancer Research, Lausanne, Switzerland.
Jazyk: angličtina
Zdroj: Placenta [Placenta] 2024 Oct; Vol. 156, pp. 55-66. Date of Electronic Publication: 2024 Sep 01.
DOI: 10.1016/j.placenta.2024.08.015
Abstrakt: The first trimester placenta is very rarely investigated for placental vascular formation in developmental or diseased contexts. Defects in placental formation can cause heart defects in the fetus, and vice versa. Determining the causality is therefore difficult as both organs develop concurrently and express many of the same genes. Here, we performed a systematic review to determine feto-placental and coronary endothelial genes implicated in miscarriages, stillbirth and congenital heart defects (CHD) from human genome wide screening studies. 4 single cell RNAseq datasets from human first/early second trimester cardiac and placental samples were queried to generate a list of 1187 endothelial genes. This broad list was cross-referenced with genes implicated in the pregnancy disorders above. 39 papers reported feto-placental and cardiac coronary endothelial genes, totalling 612 variants. Vascular gene variants were attributed to the incidence of miscarriage (8 %), CHD (4 %) and stillbirth (3 %). The most common genes for CHD (NOTCH, DST, FBN1, JAG1, CHD4), miscarriage (COL1A1, HERC1), and stillbirth (AKAP9, MYLK), were involved in blood vessel and cardiac valve formation, with roles in endothelial differentiation, angiogenesis, extracellular matrix signaling, growth factor binding and cell adhesion. NOTCH1, AKAP12, CHD4, LAMC1 and SOS1 showed greater relative risk ratios with CHD. Many of the vascular genes identified were expressed highly in both placental and heart EC populations. Both feto-placental and cardiac vascular genes are likely to result in poor endothelial cell development and function during human pregnancy that leads to higher risk of miscarriage, congenital heart disease and stillbirth.
Competing Interests: Declaration of competing interest The authors have no interests to declare.
(Copyright © 2024 Elsevier Ltd. All rights reserved.)
Databáze: MEDLINE
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