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Activation of an Endogenous Opsin 3 Light Receptor Mediates Photo-Relaxation of Pre-Contracting Late Gestation Human Uterine Smooth Muscle Ex Vivo

Authors
  • Yim, Peter D.1
  • Hyuga, Shunsuke1
  • Wu, Amy D.1
  • Dan, William1
  • Vink, Joy Y.2
  • Gallos, George1
  • 1 Columbia University, 622 168th Street, New York, NY, USA , New York (United States)
  • 2 Columbia University, New York, NY, USA , New York (United States)
Type
Published Article
Journal
Reproductive Sciences
Publisher
SAGE Publications
Publication Date
Mar 12, 2020
Volume
27
Issue
9
Pages
1791–1801
Identifiers
DOI: 10.1007/s43032-020-00180-z
Source
Springer Nature
Keywords
License
Yellow

Abstract

Spontaneous preterm birth (sPTB) remains a worldwide healthcare challenge. Preterm labor (PTL) is thought to be the largest reversible cause of sPTB, but current tocolytic therapies are ineffective and associated with systemic side effects from chronic use. Therefore, identifying novel mechanisms that promote human uterine smooth muscle (hUSM) relaxation is essential to improving clinical management of PTL. Here, we aimed to determine if an extraocular opsin receptor (OPN 3,4,5) system is expressed in pregnant hUSM and to characterize how photo-mediated relaxation of pre-contracting hUSM may be facilitated by external application of light. Translational studies were performed with hUSM from healthy late gestation patients (n = 8) and non-pregnant, similarly aged patients undergoing hysterectomy (n = 4). First, RT-PCR screened for mRNA coding for components of the classical extraocular light receptors (OPN 3,4,5). We found a restricted repertoire of opsin receptors (OPN3) expressed in pregnant hUSM tissue. Immunohistochemistry was performed to confirm protein expression. Pre-contracting late gestation hUSM strips were studied in functional organ bath studies to determine if photo-mediated relaxation is intensity or wavelength dependent. Functional organ bath studies revealed acute photo-mediated relaxation occurring in an intensity- and wavelength-dependent manner. Finally, coimmunoprecipitation of OPN3 with Gs following light activation suggests that a component of photo-relaxation occurs via G protein-coupled receptor machinery. This is the first report of light-mediated relaxation of pre-contracted human myometrium. Activation of endogenous light receptors on human myometrium may become a novel, non-invasive tocolytic strategy.

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