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

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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

Original languageEnglish
Pages (from-to)32-40
Number of pages9
JournalPlacenta
Volume123
DOIs
Published1 Jun 2022

Bibliographical note

Funding Information: We have previously reported that aldosterone increases PlGF expression in isolated trophoblasts [ 36 ]. Our current findings support this assumption and underline the regulatory role of aldosterone. Given the stimulatory capacity of aldosterone on PlGF, a regulator central to maternal angiogenic signalling, these findings are crucial. The systemic role for aldosterone is supported by the finding that sFlt-1 efflux from the placenta is unaltered. This precludes a potentially adverse antiangiogenic event, which is contributed to aldosterone in other vascular beds in the non-pregnant condition [ 37 , 38 ]. The idea that there is a stimulatory effect on PlGF was supported by a tendency for higher transcription of PlGF within the perfused cotyledon. Our findings agree with previous studies that have demonstrated that exposure of vessels to aldosterone in models of atherosclerosis show enhanced PlGF expression, mediated by a mineralocorticoid responsive element in the promoter region of plgf [ 39 , 40 ]. Funding Information: This project was supported by the Swiss National Science Foundation (SNSF) (Grant No. 310030_149958 ), through the National Centre of Competence in Research (NCCR) TransCure , University of Bern, Switzerland and the Stiftung Lindenhof Bern (Grant No. 17-15-F ), Switzerland. Publisher Copyright: © 2022 The Authors

King's Authors

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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