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Sperm Cholesterol Content Modifies Sperm Function and TRPV1-Mediated Sperm Migration

descriptionPublicationkeyboard_double_arrow_right Article , Other literature type 18 Mar 2021 Italy Publisher:MDPI AGJournal:International Journal of Molecular Sciences, volume 22, page 3,126 (eissn: 1422-0067,

Authors: De Toni L.; Sabovic I.; De Filippis V.; Acquasaliente L.; Peterle D.; Guidolin D.; Sut S.; +3 Authors

doi: 10.3390/ijms22063126

pmid: 33803867

pmc: PMC8003190

handle: 11577/3390708

Sperm Cholesterol Content Modifies Sperm Function and TRPV1-Mediated Sperm Migration

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Abstract

Transient receptor potential channels-vanilloid receptor 1 (TRPV1) regulates thermotaxis in sperm-oriented motility. We investigated the role of membrane cholesterol (Chol) on TRPV1-mediated human sperm migration. Semen samples were obtained from five normozoospemic healthy volunteers. Sperm membrane Chol content, quantified by liquid chromatography-mass spectrometry, was modified by incubating cells with 2-hydroxypropyl-ß-cyclodextrin (CD) or the complex between CD and Chol (CD:Chol). The effect on sperm migration on a 10 μM capsaicin gradient (CPS), a TRPV1 agonist, was then investigated. Motility parameters were evaluated by Sperm Class Analyser. Intracellular calcium concentration and acrosome reaction were measured by staining with calcium orange and FITC-conjugated anti-CD46 antibody, respectively. TRPV1-Chol interaction was modelled by computational molecular-modelling (MM). CD and CD:Chol, respectively, reduced and increased membrane Chol content in a dose-dependent manner, resulting in a dose-dependent increase and reduction of sperm migration in a CPS gradient. MM confirmed a specific interaction of Chol with a TRPV1 domain that appeared precluded to the Chol epimer epicholesterol (Epi-Chol). Accordingly, CD:Epi-Chol was significantly less efficient than CD:Chol, in reducing sperm migration under CPS gradient. Chol inhibits TRPV1-mediated sperm function by directly interacting with a consensus sequence of the receptor.

Country

Italy

Related Organizations

University of Padua
Italy
University of Brescia
Italy

Keywords

epicholesterol, Adult, Male, Models, Molecular, Cyclodextrins, molecular modeling, Cell Membrane, TRPV Cation Channels, Spermatozoa, sperm membrane, Article, Cholesterol, Cholesterol recognition amino acid consensus sequence; Epicholesterol; Molecular modeling; Sperm membrane; Thermotaxis; Adult; Cell Membrane; Cholesterol; Cyclodextrins; Humans; Male; Models, Molecular; Spermatozoa; TRPV Cation Channels; Sperm Motility, Sperm Motility, Humans, thermotaxis, cholesterol recognition amino acid consensus sequence

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