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      • Record: found
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      Significance of transient receptor potential vanilloid 4 and aquaporin 5 co-expression in the rat uterus at term

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          Abstract

          Aims

          Aquaporins (AQPs) are channel proteins that facilitate the rapid passive movement of water. In our studies it was proved that the decreased AQP5 expression is followed by the increase of uterine contractility. The transient receptor potential vanilloid 4 (TRPV4) is a calcium channel, which is activated in response to osmotic changes. Our aim was to determine the possible role of AQP5 in this osmotic regulation of TRPV4, thus in pregnant uterine contraction.

          Main methods

          We used RT-PCR and Western blot techniques for the detection of the TRPV4 expression during pregnancy in rat uterus. The localization of AQP5 and TRPV4 was determined by immunohistochemical studies. The role of TRPV4 in uterus contraction was investigated in an isolated organ bath system. In vitro uterus contractions were stimulated with KCl and its effect was investigated with the selective TRPV4 agonist (RN1747) and antagonist (RN1734).

          Key findings

          The TRPV4 expression continuously increased from day 18 to the last day of pregnancy. The co-expression of TRPV4 and AQP5 in the myometrium and endometrium was determined in the late pregnant uterus. The TRPV4 antagonist and agonist significantly decreased and increased uterine contraction, respectively, especially on the last day of pregnancy.

          Significance

          We presume the decreased AQP5 expression triggers hypertonic stress, which activates TRPV4 and increases uterus contraction on the day of labor. Based on these findings, we suppose the TRPV4 effect on uterus contraction is AQP5 control, which could be a new target in preterm birth therapy.

          Abstract

          Obstetrics; Pharmacology; Physiology; Pregnancy; Molecular biology; Reproductive system; AQP5; Pregnancy; Preterm birth; TRPV4

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          Most cited references26

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          Single-step method of RNA isolation by acid guanidinium thiocyanate-phenol-chloroform extraction.

          P. Chomczynski, N Sacchi (1987)
          A new method of total RNA isolation by a single extraction with an acid guanidinium thiocyanate-phenol-chloroform mixture is described. The method provides a pure preparation of undegraded RNA in high yield and can be completed within 4 h. It is particularly useful for processing large numbers of samples and for isolation of RNA from minute quantities of cells or tissue samples.
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            An aquaporin-4/transient receptor potential vanilloid 4 (AQP4/TRPV4) complex is essential for cell-volume control in astrocytes.

            Stefano Ferroni, Marco Caprini, Valentina Benfenati … (2011)
            Regulatory volume decrease (RVD) is a key mechanism for volume control that serves to prevent detrimental swelling in response to hypo-osmotic stress. The molecular basis of RVD is not understood. Here we show that a complex containing aquaporin-4 (AQP4) and transient receptor potential vanilloid 4 (TRPV4) is essential for RVD in astrocytes. Astrocytes from AQP4-KO mice and astrocytes treated with TRPV4 siRNA fail to respond to hypotonic stress by increased intracellular Ca(2+) and RVD. Coimmunoprecipitation and immunohistochemistry analyses show that AQP4 and TRPV4 interact and colocalize. Functional analysis of an astrocyte-derived cell line expressing TRPV4 but not AQP4 shows that RVD and intracellular Ca(2+) response can be reconstituted by transfection with AQP4 but not with aquaporin-1. Our data indicate that astrocytes contain a TRPV4/AQP4 complex that constitutes a key element in the brain's volume homeostasis by acting as an osmosensor that couples osmotic stress to downstream signaling cascades.
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              Novel concepts on pregnancy clocks and alarms: redundancy and synergy in human parturition

              Ramkumar Menon, Elizabeth Bonney, Jennifer Condon … (2016)
              The signals and mechanisms that synchronize the timing of human parturition remain a mystery and a better understanding of these processes is essential to avert adverse pregnancy outcomes. Although our insights into human labor initiation have been informed by studies in animal models, the timing of parturition relative to fetal maturation varies among viviparous species, indicative of phylogenetically different clocks and alarms; but what is clear is that important common pathways must converge to control the birth process. For example, in all species, parturition involves the transition of the myometrium from a relaxed to a highly excitable state, where the muscle rhythmically and forcefully contracts, softening the cervical extracellular matrix to allow distensibility and dilatation and thus a shearing of the fetal membranes to facilitate their rupture. We review a number of theories promulgated to explain how a variety of different timing mechanisms, including fetal membrane cell senescence, circadian endocrine clocks, and inflammatory and mechanical factors, are coordinated as initiators and effectors of parturition. Many of these factors have been independently described with a focus on specific tissue compartments. In this review, we put forth the core hypothesis that fetal membrane (amnion and chorion) senescence is the initiator of a coordinated, redundant signal cascade leading to parturition. Whether modified by oxidative stress or other factors, this process constitutes a counting device, i.e. a clock, that measures maturation of the fetal organ systems and the production of hormones and other soluble mediators (including alarmins) and that promotes inflammation and orchestrates an immune cascade to propagate signals across different uterine compartments. This mechanism in turn sensitizes decidual responsiveness and eventually promotes functional progesterone withdrawal in the myometrium, leading to increased myometrial cell contraction and the triggering of parturition. Linkage of these processes allows convergence and integration of the gestational clocks and alarms, prompting a timely and safe birth. In summary, we provide a comprehensive synthesis of the mediators that contribute to the timing of human labor. Integrating these concepts will provide a better understanding of human parturition and ultimately improve pregnancy outcomes.
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                Author and article information

                Contributors
                Eszter Ducza
                Róbert Gáspár
                Journal
                Journal ID (nlm-ta): Heliyon
                Journal ID (iso-abbrev): Heliyon
                Title: Heliyon
                Publisher: Elsevier
                ISSN (Electronic): 2405-8440
                Publication date PMC-release: 22 October 2019
                Publication date Collection: October 2019
                Publication date (Electronic): 22 October 2019
                Volume: 5
                Issue: 10
                Electronic Location Identifier: e02697
                Affiliations
                [a ]Department of Pharmacodynamics and Biopharmacy, University of Szeged, Hungary
                [b ]Department of Pharmacology and Pharmacotherapy, Medical School, University of Pécs, Pécs, Hungary
                [c ]János Szentágothai Research Center & Centre for Neuroscience, University of Pécs, Hungary
                [d ]Department of Pharmacology, Faculty of Pharmacy, University of Pécs, Pécs, Hungary
                [e ]Department of Pharmacology and Pharmacotherapy , Interdisciplinary Excellence Centre, University of Szeged, Hungary
                Author notes
                [∗ ]Corresponding author. ducza@ 123456pharm.u-szeged.hu
                [∗∗ ]Corresponding author. gaspar.robert@ 123456med.u-szeged.hu
                Article
                Publisher ID: S2405-8440(19)36357-1 Publisher ID: e02697
                DOI: 10.1016/j.heliyon.2019.e02697
                PMC ID: 6820280
                SO-VID: dc3dce61-91f3-4b41-8a44-3d22c1cd8602
                Copyright © © 2019 The Authors. Published by Elsevier Ltd.
                License:

                This is an open access article under the CC BY-NC-ND license (http://creativecommons.org/licenses/by-nc-nd/4.0/).

                History
                Date received : 7 February 2019
                Date revision received : 13 September 2019
                Date accepted : 16 October 2019
                Categories
                Subject: Article

                Keywords: obstetrics,pharmacology,physiology,pregnancy,molecular biology,reproductive system,aqp5,preterm birth,trpv4
                Data availability:
                Keywords: obstetrics, pharmacology, physiology, pregnancy, molecular biology, reproductive system, aqp5, preterm birth, trpv4

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