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Genetically edited human placental organoids cast new light on the role of ACE2
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Genetically edited human placental organoids cast new light on the role of ACE2
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Journal Article
Genetically edited human placental organoids cast new light on the role of ACE2
2025
Overview
ACE2 expression is altered in pregnancy disorders and
ACE2
gene variants are associated with several major pregnancy complications including small-for-gestational-age, fetal growth restriction and preeclampsia. This study utilised gene-editing to generate both
ACE2
knockout and
ACE2
rs2074192 placental organoids, facilitating mechanistic studies into the role of
ACE2
in placental development, and the effect of fetal carriage of
ACE2
rs2074192 CC, CT and TT genotypes. Parameters of cell and organoid growth were measured, together with qPCR, Western Blotting, and ELISA assessments, in all groups from both organoid models. Here, we report that
ACE2
knockout results in delayed placental cell growth and increased cell death.
ACE2
knockout organoids had lower ACE protein expression, reduced organoid diameters and asymmetrical growth. Placental organoids with the ACE2 rs2074192 TT genotype had significantly higher expression of
ACE2
mRNA and ACE2 protein with elevated ACE2:ACE expression ratio and no change in ACE protein. Despite increased expression of ACE2 protein, ACE2 enzyme activity was significantly decreased in ACE2 rs2074192 TT placental organoids. TT organoids also had reduced diameters and asymmetrical growth. Our research provides a new molecular understanding of the role of ACE2 in placental development, with potential implications for pregnancy in the carriage of the
ACE2
rs2074192 gene variant.
Publisher
Nature Publishing Group UK,Springer Nature B.V,Nature Publishing Group
Subject
/ 13/106
/ 14/63
/ 38/109
/ 38/22
/ 38/39
/ 38/44
/ 38/77
/ 38/90
/ 42
/ 45
/ 631/136
/ 631/45
/ ACE2
/ Angiotensin-converting enzyme 2
/ Angiotensin-Converting Enzyme 2 - genetics
/ Angiotensin-Converting Enzyme 2 - metabolism
/ Biomedical and Life Sciences
/ Enzyme-linked immunosorbent assay
/ Enzymes
/ Female
/ Fetuses
/ Humans
/ mRNA
/ Peptidyl-Dipeptidase A - genetics
/ Peptidyl-Dipeptidase A - metabolism
/ Placenta
/ Proteins
