Sperm Cholesterol Content Modifies Sperm Function and TRPV1-Mediated Sperm Migration.
cholesterol recognition amino acid consensus sequence
epicholesterol
molecular modeling
sperm membrane
thermotaxis
Journal
International journal of molecular sciences
ISSN: 1422-0067
Titre abrégé: Int J Mol Sci
Pays: Switzerland
ID NLM: 101092791
Informations de publication
Date de publication:
18 Mar 2021
18 Mar 2021
Historique:
received:
09
02
2021
revised:
12
03
2021
accepted:
16
03
2021
entrez:
3
4
2021
pubmed:
4
4
2021
medline:
22
4
2021
Statut:
epublish
Résumé
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.
Identifiants
pubmed: 33803867
pii: ijms22063126
doi: 10.3390/ijms22063126
pmc: PMC8003190
pii:
doi:
Substances chimiques
Cyclodextrins
0
TRPV Cation Channels
0
TRPV1 protein, human
0
Cholesterol
97C5T2UQ7J
Types de publication
Journal Article
Langues
eng
Sous-ensembles de citation
IM
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