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Placental deficiency of the (pro)renin receptor ((P)RR) reduces placental development and functional capacity

The (pro)renin receptor ((P)RR; also known as ATP6AP2) is a multifunctional receptor. The (P)RR activates the tissue renin-angiotensin system (RAS) and is also involved in regulating integral intracellular pathways such as V-ATPase and Wnt/β-catenin signalling. Given this, the (P)RR may be associate...

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Autores principales: Schofield, Lachlan G., Kahl, Richard G. S., Rodrigues, Samantha L., Fisher, Joshua J., Endacott, Saije K., Delforce, Sarah J., Lumbers, Eugenie R., Martin, Jacinta H., Pringle, Kirsty G.
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Frontiers Media S.A. 2023
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10427116/
https://www.ncbi.nlm.nih.gov/pubmed/37588662
http://dx.doi.org/10.3389/fcell.2023.1212898
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author Schofield, Lachlan G.
Kahl, Richard G. S.
Rodrigues, Samantha L.
Fisher, Joshua J.
Endacott, Saije K.
Delforce, Sarah J.
Lumbers, Eugenie R.
Martin, Jacinta H.
Pringle, Kirsty G.
author_facet Schofield, Lachlan G.
Kahl, Richard G. S.
Rodrigues, Samantha L.
Fisher, Joshua J.
Endacott, Saije K.
Delforce, Sarah J.
Lumbers, Eugenie R.
Martin, Jacinta H.
Pringle, Kirsty G.
author_sort Schofield, Lachlan G.
collection PubMed
description The (pro)renin receptor ((P)RR; also known as ATP6AP2) is a multifunctional receptor. The (P)RR activates the tissue renin-angiotensin system (RAS) and is also involved in regulating integral intracellular pathways such as V-ATPase and Wnt/β-catenin signalling. Given this, the (P)RR may be associated with essential pathways in placentation, however its role within the context of pregnancy remains poorly characterised. The first trimester/extravillous trophoblast cell line, HTR-8/SVneo, underwent an siRNA knockdown where they were incubated for 24 h with a negative control siRNA or siRNA targeting ATP6AP2 mRNA. xCELLigence real-time cell analysis was performed to assess the effect of ATP6AP2 mRNA knockdown on HTR-8/SVneo cell proliferation, migration, and invasion. In subsequent experiments, GFP-encoding lentiviral packaged gene-constructs were used to knockdown (P)RR expression in the trophectoderm of C57/BL6/CBA-F1 mouse blastocysts. Blastocysts were incubated for 6 h with vehicle (no-virus), control virus (non-targeting shRNA and GFP), or (P)RR-knockdown virus ((P)RR shRNA and GFP) before transfer into recipient pseudo-pregnant Swiss CD1 female mice. Fetal and placental tissues were collected and assessed at embryonic age (EA) 10 and 18. (P)RR levels were measured in the labyrinth zone of day 18 placentae and stereological Merz grid analysis was performed to determine the volumetric distribution of trophoblasts, fetal capillaries, and the maternal blood space. We showed that a reduction of ATP6AP2 expression in HTR-8/SVneo cells in vitro, impaired trophoblast proliferation, migration, and invasion. In vivo, decreasing placental labyrinth (P)RR expression adversely effected placental physiology, decreasing placental trophoblast number and total surface area available for exchange, while also increasing maternal blood space. Additionally, decreased (P)RR affected placental efficacy evident by the reduced fetal-placental weight ratio. Our study shows that the (P)RR is necessary for appropriate placental development and function.
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spelling pubmed-104271162023-08-16 Placental deficiency of the (pro)renin receptor ((P)RR) reduces placental development and functional capacity Schofield, Lachlan G. Kahl, Richard G. S. Rodrigues, Samantha L. Fisher, Joshua J. Endacott, Saije K. Delforce, Sarah J. Lumbers, Eugenie R. Martin, Jacinta H. Pringle, Kirsty G. Front Cell Dev Biol Cell and Developmental Biology The (pro)renin receptor ((P)RR; also known as ATP6AP2) is a multifunctional receptor. The (P)RR activates the tissue renin-angiotensin system (RAS) and is also involved in regulating integral intracellular pathways such as V-ATPase and Wnt/β-catenin signalling. Given this, the (P)RR may be associated with essential pathways in placentation, however its role within the context of pregnancy remains poorly characterised. The first trimester/extravillous trophoblast cell line, HTR-8/SVneo, underwent an siRNA knockdown where they were incubated for 24 h with a negative control siRNA or siRNA targeting ATP6AP2 mRNA. xCELLigence real-time cell analysis was performed to assess the effect of ATP6AP2 mRNA knockdown on HTR-8/SVneo cell proliferation, migration, and invasion. In subsequent experiments, GFP-encoding lentiviral packaged gene-constructs were used to knockdown (P)RR expression in the trophectoderm of C57/BL6/CBA-F1 mouse blastocysts. Blastocysts were incubated for 6 h with vehicle (no-virus), control virus (non-targeting shRNA and GFP), or (P)RR-knockdown virus ((P)RR shRNA and GFP) before transfer into recipient pseudo-pregnant Swiss CD1 female mice. Fetal and placental tissues were collected and assessed at embryonic age (EA) 10 and 18. (P)RR levels were measured in the labyrinth zone of day 18 placentae and stereological Merz grid analysis was performed to determine the volumetric distribution of trophoblasts, fetal capillaries, and the maternal blood space. We showed that a reduction of ATP6AP2 expression in HTR-8/SVneo cells in vitro, impaired trophoblast proliferation, migration, and invasion. In vivo, decreasing placental labyrinth (P)RR expression adversely effected placental physiology, decreasing placental trophoblast number and total surface area available for exchange, while also increasing maternal blood space. Additionally, decreased (P)RR affected placental efficacy evident by the reduced fetal-placental weight ratio. Our study shows that the (P)RR is necessary for appropriate placental development and function. Frontiers Media S.A. 2023-08-01 /pmc/articles/PMC10427116/ /pubmed/37588662 http://dx.doi.org/10.3389/fcell.2023.1212898 Text en Copyright © 2023 Schofield, Kahl, Rodrigues, Fisher, Endacott, Delforce, Lumbers, Martin and Pringle. https://creativecommons.org/licenses/by/4.0/This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY). The use, distribution or reproduction in other forums is permitted, provided the original author(s) and the copyright owner(s) are credited and that the original publication in this journal is cited, in accordance with accepted academic practice. No use, distribution or reproduction is permitted which does not comply with these terms.
spellingShingle Cell and Developmental Biology
Schofield, Lachlan G.
Kahl, Richard G. S.
Rodrigues, Samantha L.
Fisher, Joshua J.
Endacott, Saije K.
Delforce, Sarah J.
Lumbers, Eugenie R.
Martin, Jacinta H.
Pringle, Kirsty G.
Placental deficiency of the (pro)renin receptor ((P)RR) reduces placental development and functional capacity
title Placental deficiency of the (pro)renin receptor ((P)RR) reduces placental development and functional capacity
title_full Placental deficiency of the (pro)renin receptor ((P)RR) reduces placental development and functional capacity
title_fullStr Placental deficiency of the (pro)renin receptor ((P)RR) reduces placental development and functional capacity
title_full_unstemmed Placental deficiency of the (pro)renin receptor ((P)RR) reduces placental development and functional capacity
title_short Placental deficiency of the (pro)renin receptor ((P)RR) reduces placental development and functional capacity
title_sort placental deficiency of the (pro)renin receptor ((p)rr) reduces placental development and functional capacity
topic Cell and Developmental Biology
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10427116/
https://www.ncbi.nlm.nih.gov/pubmed/37588662
http://dx.doi.org/10.3389/fcell.2023.1212898
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