Effects of aldosterone on the human placenta: Insights from placental perfusion studies

Hiten D Mistry; Rahel Klossner; Sampada Kallol; Michael P Lüthi; Ruedi Moser; Henning Schneider; Edgar C Ontsouka; Lesia O Kurlak; Markus G Mohaupt; Christiane Albrecht

doi:10.1016/j.placenta.2022.03.129

Effects of aldosterone on the human placenta: Insights from placental perfusion studies

Placenta. 2022 Jun 1:123:32-40. doi: 10.1016/j.placenta.2022.03.129. Epub 2022 May 2.

Authors

Affiliations

¹ Department of Women's and Children's Health, King's College London, UK.
² Department of Nephrology, Hypertension and Clinical Pharmacology, University of Bern, Switzerland; Department of Internal Medicine, Lindenhofgruppe Bern, Switzerland.
³ Institute of Biochemistry and Molecular Medicine, University of Bern, Switzerland; Swiss National Center of Competence in Research, NCCR TransCure, University of Bern, Switzerland.
⁴ Institute of Biochemistry and Molecular Medicine, University of Bern, Switzerland.
⁵ School of Medicine (Stroke Research), University of Nottingham, UK.
⁶ 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.
⁷ 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.

PMID: 35537250
DOI: 10.1016/j.placenta.2022.03.129

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.

Keywords: Aldosterone; IL-10; PlGF; Placenta perfusion; TNF-α; sFlt-1.

Publication types

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

MeSH terms

Aldosterone / metabolism
Female
Humans
Interleukin-10 / metabolism
Perfusion
Placenta Growth Factor
Placenta* / metabolism
Pre-Eclampsia* / metabolism
Pregnancy
Pregnancy Outcome
RNA, Messenger / metabolism
Tumor Necrosis Factor-alpha / metabolism
Vascular Endothelial Growth Factor Receptor-1 / metabolism

Substances

RNA, Messenger
Tumor Necrosis Factor-alpha
Interleukin-10
Placenta Growth Factor
Aldosterone
Vascular Endothelial Growth Factor Receptor-1

Grants and funding

FS/15/32/31604/BHF_/British Heart Foundation/United Kingdom