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Effect of cariporide on ram sperm pH regulation and motility: possible role of NHE1.
- Source :
-
Reproduction (Cambridge, England) [Reproduction] 2018 May; Vol. 155 (5), pp. 433-445. Date of Electronic Publication: 2018 Feb 28. - Publication Year :
- 2018
-
Abstract
- Sperm motility, a feature essential for in vivo fertilization, is influenced by intracellular pH (pH <subscript>i</subscript> ) homeostasis. Several mechanisms are involved in pH <subscript>i</subscript> regulation, among which sodium-hydrogen exchangers (NHEs), a family of integral transmembrane proteins that catalyze the exchange of Na <superscript>+</superscript> for H <superscript>+</superscript> across lipid bilayers. A preliminary characterization of NHE activity and kinetic parameters, followed by analysis of the expression and localization of the protein in ram spermatozoa was performed. NHE activity showed an apparent K <subscript>m</subscript> for external Na <superscript>+</superscript> of 17.61 mM. Immunoblotting revealed a molecular mass of 85 kDa. Immunolocalization pattern showed some species-specific aspects, such as positive labeling at the equatorial region of the sperm head. Cariporide, a selective NHE1 inhibitor, significantly reduced pH <subscript>i</subscript> recovery (85%). Similarly, exposure to cariporide significantly inhibited different motility parameters, including those related to sperm capacitation. In vitro fertilization (IVF) was not affected by cariporide, possibly due to the non-dramatic, although significant, drop in motility and velocity parameters or due to prolonged exposure during IVF, which may have caused progressive loss of its inhibitory effect. In conclusion, this is the first study documenting, in a large animal model (sheep) of well-known translational relevance, a direct functional role of NHE on sperm pH <subscript>i</subscript> and motility. The postulated specificity of cariporide toward isoform 1 of the Na <superscript>+</superscript> /H <superscript>+</superscript> exchanger seems to suggest that NHE1 may contribute to the observed effects on sperm cell functionality.<br /> (© 2018 Society for Reproduction and Fertility.)
- Subjects :
- Animals
Hydrogen-Ion Concentration
Male
Sheep
Sperm Capacitation drug effects
Sperm Capacitation physiology
Sperm Motility physiology
Spermatozoa metabolism
Guanidines pharmacology
Sodium-Hydrogen Exchanger 1 metabolism
Sperm Motility drug effects
Spermatozoa drug effects
Sulfones pharmacology
Subjects
Details
- Language :
- English
- ISSN :
- 1741-7899
- Volume :
- 155
- Issue :
- 5
- Database :
- MEDLINE
- Journal :
- Reproduction (Cambridge, England)
- Publication Type :
- Academic Journal
- Accession number :
- 29491124
- Full Text :
- https://doi.org/10.1530/REP-17-0456