Soluble adenylyl cyclase inhibition prevents human sperm functions essential for fertilization
| Autor: | Thomas Rossetti, Lis C. Puga Molina, Makoto Fushimi, Jochen Buck, Dagmar Wachten, Dario Krapf, Lonny R. Levin, Lubna Ghanem, Carla Ritagliati, Melanie Balbach, Navpreet Kaur, Jacob Ferreira, Peter T. Meinke, Jan N. Hansen, Celia M. Santi |
|---|---|
| Rok vydání: | 2021 |
| Předmět: |
Male
Embryology endocrine system Acrosome reaction Motility Biology ADCY10 Mice Human fertilization Pregnancy Capacitation Genetics medicine Animals Humans Protein kinase A education Molecular Biology Sperm motility Cells Cultured reproductive and urinary physiology Original Research Mice Knockout Mice Inbred ICR education.field_of_study urogenital system Chemistry Obstetrics and Gynecology Cell Biology Soluble adenylyl cyclase Oocyte Spermatozoa Sperm Cell biology Mice Inbred C57BL medicine.anatomical_structure Reproductive Medicine Fertilization Adenylyl Cyclase Inhibitors Female Developmental Biology Adenylyl Cyclases |
| Zdroj: | Mol Hum Reprod |
| Popis: | 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. |
| Databáze: | OpenAIRE |
| Externí odkaz: |
|