Soluble adenylyl cyclase inhibition prevents human sperm functions essential for fertilization.
acrosome reaction
capacitation
contraception
cyclic AMP
sperm motility
Journal
Molecular human reproduction
ISSN: 1460-2407
Titre abrégé: Mol Hum Reprod
Pays: England
ID NLM: 9513710
Informations de publication
Date de publication:
01 09 2021
01 09 2021
Historique:
received:
28
04
2021
revised:
16
08
2021
pubmed:
1
9
2021
medline:
27
1
2022
entrez:
31
8
2021
Statut:
ppublish
Résumé
Soluble adenylyl cyclase (sAC: ADCY10) has been genetically confirmed to be essential for male fertility in mice and humans. In mice, ex vivo studies of dormant, caudal epididymal sperm demonstrated that sAC is required for initiating capacitation and activating motility. We now use an improved sAC inhibitor, TDI-10229, for a comprehensive analysis of sAC function in mouse and human sperm. In contrast to caudal epididymal mouse sperm, human sperm are collected post-ejaculation, after sAC activity has already been stimulated. In addition to preventing the capacitation-induced stimulation of sAC and protein kinase A activities, tyrosine phosphorylation, alkalinization, beat frequency and acrosome reaction in dormant mouse sperm, sAC inhibitors interrupt each of these capacitation-induced changes in ejaculated human sperm. Furthermore, we show for the first time that sAC is required during acrosomal exocytosis in mouse and human sperm. These data define sAC inhibitors as candidates for non-hormonal, on-demand contraceptives suitable for delivery via intravaginal devices in women.
Identifiants
pubmed: 34463764
pii: 6360468
doi: 10.1093/molehr/gaab054
pmc: PMC8473925
pii:
doi:
Substances chimiques
Adenylyl Cyclase Inhibitors
0
ADCY10 protein, human
EC 4.6.1.1
Adenylyl Cyclases
EC 4.6.1.1
Types de publication
Journal Article
Research Support, N.I.H., Extramural
Research Support, Non-U.S. Gov't
Langues
eng
Sous-ensembles de citation
IM
Subventions
Organisme : NIGMS NIH HHS
ID : T32 GM073546
Pays : United States
Organisme : NIA NIH HHS
ID : F31 AG069501
Pays : United States
Organisme : NICHD NIH HHS
ID : R01 HD088571
Pays : United States
Organisme : NICHD NIH HHS
ID : R01 HD069631
Pays : United States
Organisme : NICHD NIH HHS
ID : F31 HD105363
Pays : United States
Organisme : NICHD NIH HHS
ID : P50 HD100549
Pays : United States
Informations de copyright
© The Author(s) 2021. Published by Oxford University Press on behalf of European Society of Human Reproduction and Embryology. All rights reserved. For permissions, please email: journals.permissions@oup.com.
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