TRPV2, a novel player in the human ovary and human granulosa cells

Author:

Eubler Katja1,Caban Karolina M2,Dissen Gregory A3,Berg Ulrike4,Berg Dieter4,Herrmann Carola1,Kreitmair Nicole1,Tiefenbacher Astrid1,Fröhlich Thomas2ORCID,Mayerhofer Artur1ORCID

Affiliation:

1. Biomedical Center Munich (BMC), Cell Biology, Anatomy III, Faculty of Medicine, Ludwig-Maximilian-University (LMU) Munich , Planegg-Martinsried, Germany

2. Laboratory for Functional Genome Analysis LAFUGA, Gene Center, LMU Munich , Munich, Germany

3. Molecular Virology Core, Oregon Health & Science University (OHSU), Oregon National Primate Research Center , Beaverton, OR, USA

4. A.R.T. Bogenhausen , Munich, Germany

Abstract

Abstract The cation channel ‘transient receptor potential vanilloid 2’ (TRPV2) is activated by a broad spectrum of stimuli, including mechanical stretch, endogenous and exogenous chemical compounds, hormones, growth factors, reactive oxygen species, and cannabinoids. TRPV2 is known to be involved in inflammatory and immunological processes, which are also of relevance in the ovary. Yet, neither the presence nor possible roles of TRPV2 in the ovary have been investigated. Data mining indicated expression, for example, in granulosa cells (GCs) of the human ovary in situ, which was retained in cultured GCs derived from patients undergoing medical reproductive procedures. We performed immunohistochemistry of human and rhesus monkey ovarian sections and then cellular studies in cultured GCs, employing the preferential TRPV2 agonist cannabidiol (CBD). Immunohistochemistry showed TRPV2 staining in GCs of large antral follicles and corpus luteum but also in theca, endothelial, and stromal cells. TRPV2 transcript and protein levels increased upon administration of hCG or forskolin. Acutely, application of the agonist CBD elicited transient Ca2+ fluxes, which was followed by the production and secretion of several inflammatory factors, especially COX2, IL6, IL8, and PTX3, in a time- and dose-dependent manner. CBD interfered with progesterone synthesis and altered both the proteome and secretome, as revealed by a proteomic study. While studies are somewhat hampered by the lack of highly specific TRPV2 agonist or antagonists, the results pinpoint TRPV2 as a modulator of inflammation with possible roles in human ovarian (patho-)physiology. Finally, as TRPV2 is activated by cannabinoids, their possible ovarian actions should be further evaluated.

Funder

Deutsche Forschungsgemeinschaft

National Institutes of Health

Publisher

Oxford University Press (OUP)

Subject

Cell Biology,Developmental Biology,Obstetrics and Gynecology,Genetics,Molecular Biology,Embryology,Reproductive Medicine

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