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Effects of aldosterone on the human placenta: Insights from placental perfusion studies.
Placenta. 2022 Jun 01; 123:32-40.P

Abstract

INTRODUCTION

In pregnancy, aldosterone is linked to maternal plasma volume expansion, improved fetal and placental growth/angiogenesis and reduced maternal blood pressure. Aldosterone levels are low in women with pre-eclampsia. Given the placental growth properties of aldosterone in pregnancy, we hypothesised that increased aldosterone improves placental function ex vivo. We applied aldosterone in the dual human placenta perfusion model and analysed specific regulatory markers.

METHODS

A single cotyledon was perfused using a trimodal perfusion setup consisting of a control phase (CP; basic perfusion medium (BPM) alone) and two consecutive experimental phases (EP1/EP2; BPM supplemented with 1.5 x 10-9M and 1.5 x 10-7M aldosterone, respectively). CP and EP1/EP2 were conducted in closed circuits lasting 2 h each. Quality/time control perfusions using BPM alone were performed for 360 min to distinguish time-dependent effects from aldosterone-related effects. Perfusates were assessed for control parameters (pH/pO2/pCO2/glucose/lactate/creatinine/antipyrine). Maternal perfusates were analysed for placental growth factor (PlGF), soluble fms-like tyrosine kinase-1 (sFlt-1), interleukin-10 (IL-10) and tumour necrosis factor-alpha (TNF-α) using ELISAs. mRNA expression of abovementioned factors was measured by qPCR in post-perfusion tissue.

RESULTS

Data from quality/time control perfusions indicated that TNF-α and IL-10 release continuously increased over time. Contrary, in the trimodal perfusion setup the application of aldosterone decreased TNF-α secretion (P < 0.05, EP1/EP2 vs CP, 120 min) and increased PlGF release (P < 0.05, EP1 vs CP, 90/120 min) into the maternal perfusates. mRNA expression followed similar trends, but did not reach significance.

DISCUSSION

Our ex vivo placental perfusion data suggest that increasing aldosterone promotes anti-inflammatory and pro-angiogenic factors, which could positively contribute to healthy pregnancy outcomes.

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Publisher Full Text (DOI)

Authors+Show Affiliations

Mistry HD
Department of Women's and Children's Health, King's College London, UK.
Klossner R
Department of Nephrology, Hypertension and Clinical Pharmacology, University of Bern, Switzerland; Department of Internal Medicine, Lindenhofgruppe Bern, Switzerland.
Kallol S
Institute of Biochemistry and Molecular Medicine, University of Bern, Switzerland; Swiss National Center of Competence in Research, NCCR TransCure, University of Bern, Switzerland.
Lüthi MP
Institute of Biochemistry and Molecular Medicine, University of Bern, Switzerland; Swiss National Center of Competence in Research, NCCR TransCure, University of Bern, Switzerland.
Moser R
Institute of Biochemistry and Molecular Medicine, University of Bern, Switzerland; Swiss National Center of Competence in Research, NCCR TransCure, University of Bern, Switzerland.
Schneider H
Institute of Biochemistry and Molecular Medicine, University of Bern, Switzerland.
Ontsouka EC
Institute of Biochemistry and Molecular Medicine, University of Bern, Switzerland.
Kurlak LO
School of Medicine (Stroke Research), University of Nottingham, UK.
Mohaupt MG
Department of Women's and Children's Health, King's College London, UK; Department of Nephrology, Hypertension and Clinical Pharmacology, University of Bern, Switzerland; Department of Internal Medicine, Lindenhofgruppe Bern, Switzerland.
Albrecht C
Institute of Biochemistry and Molecular Medicine, University of Bern, Switzerland; Swiss National Center of Competence in Research, NCCR TransCure, University of Bern, Switzerland. Electronic address: christiane.albrecht@ibmm.unibe.ch.

MeSH

AldosteroneFemaleHumansInterleukin-10PerfusionPlacentaPlacenta Growth FactorPre-EclampsiaPregnancyPregnancy OutcomeRNA, MessengerTumor Necrosis Factor-alphaVascular Endothelial Growth Factor Receptor-1

Pub Type(s)

Journal Article
Research Support, Non-U.S. Gov't

Language

eng

PubMed ID

35537250

Citation

Mistry, Hiten D., et al. "Effects of Aldosterone On the Human Placenta: Insights From Placental Perfusion Studies." Placenta, vol. 123, 2022, pp. 32-40.
Mistry HD, Klossner R, Kallol S, et al. Effects of aldosterone on the human placenta: Insights from placental perfusion studies. Placenta. 2022;123:32-40.
Mistry, H. D., Klossner, R., Kallol, S., Lüthi, M. P., Moser, R., Schneider, H., Ontsouka, E. C., Kurlak, L. O., Mohaupt, M. G., & Albrecht, C. (2022). Effects of aldosterone on the human placenta: Insights from placental perfusion studies. Placenta, 123, 32-40. https://doi.org/10.1016/j.placenta.2022.03.129
Mistry HD, et al. Effects of Aldosterone On the Human Placenta: Insights From Placental Perfusion Studies. Placenta. 2022 06 1;123:32-40. PubMed PMID: 35537250.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - Effects of aldosterone on the human placenta: Insights from placental perfusion studies. AU - Mistry,Hiten D, AU - Klossner,Rahel, AU - Kallol,Sampada, AU - Lüthi,Michael P, AU - Moser,Ruedi, AU - Schneider,Henning, AU - Ontsouka,Edgar C, AU - Kurlak,Lesia O, AU - Mohaupt,Markus G, AU - Albrecht,Christiane, Y1 - 2022/05/02/ PY - 2021/07/15/received PY - 2022/03/21/revised PY - 2022/03/23/accepted PY - 2022/5/11/pubmed PY - 2022/5/25/medline PY - 2022/5/10/entrez KW - Aldosterone KW - IL-10 KW - PlGF KW - Placenta perfusion KW - TNF-α KW - sFlt-1 SP - 32 EP - 40 JF - Placenta JO - Placenta VL - 123 N2 - INTRODUCTION: In pregnancy, aldosterone is linked to maternal plasma volume expansion, improved fetal and placental growth/angiogenesis and reduced maternal blood pressure. Aldosterone levels are low in women with pre-eclampsia. Given the placental growth properties of aldosterone in pregnancy, we hypothesised that increased aldosterone improves placental function ex vivo. We applied aldosterone in the dual human placenta perfusion model and analysed specific regulatory markers. METHODS: A single cotyledon was perfused using a trimodal perfusion setup consisting of a control phase (CP; basic perfusion medium (BPM) alone) and two consecutive experimental phases (EP1/EP2; BPM supplemented with 1.5 x 10-9M and 1.5 x 10-7M aldosterone, respectively). CP and EP1/EP2 were conducted in closed circuits lasting 2 h each. Quality/time control perfusions using BPM alone were performed for 360 min to distinguish time-dependent effects from aldosterone-related effects. Perfusates were assessed for control parameters (pH/pO2/pCO2/glucose/lactate/creatinine/antipyrine). Maternal perfusates were analysed for placental growth factor (PlGF), soluble fms-like tyrosine kinase-1 (sFlt-1), interleukin-10 (IL-10) and tumour necrosis factor-alpha (TNF-α) using ELISAs. mRNA expression of abovementioned factors was measured by qPCR in post-perfusion tissue. RESULTS: Data from quality/time control perfusions indicated that TNF-α and IL-10 release continuously increased over time. Contrary, in the trimodal perfusion setup the application of aldosterone decreased TNF-α secretion (P < 0.05, EP1/EP2 vs CP, 120 min) and increased PlGF release (P < 0.05, EP1 vs CP, 90/120 min) into the maternal perfusates. mRNA expression followed similar trends, but did not reach significance. DISCUSSION: Our ex vivo placental perfusion data suggest that increasing aldosterone promotes anti-inflammatory and pro-angiogenic factors, which could positively contribute to healthy pregnancy outcomes. SN - 1532-3102 UR - https://www.unboundmedicine.com/medline/citation/35537250/full_citation DB - PRIME DP - Unbound Medicine ER -
Grapherence [↓3]

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