Progesterone Accelerates the Completion of Sperm Capacitation and Activates CatSper Channel in Spermatozoa from the Rhesus Macaque.
During transit through the female reproductive tract, mammalian spermatozoa are exposed to increasing concentrations of progesterone (P4) released by the cumulus oophorus. P4 triggers massive calcium influx into human sperm through activation of the sperm-specific calcium channel CatSper. These properties of human spermatozoa are thought to be unique since CatSper is not progesterone sensitive in rodent sperm. Here, by performing patch clamp recording from spermatozoa from rhesus macaque for the first time, we report that they express P4-sensitive CatSper channel identically to human sperm and react to P4 by inducing responsiveness to zona pellucida, unlike human sperm, which respond directly to P4. We have also determined the physiologic levels of P4 capable of inducing capacitation-associated changes in macaque sperm. Progesterone (1 μM) induced up to a 3-fold increase in the percentage of sperm undergoing the zona pellucida-induced acrosome reaction with the lowest threshold as low as 10 nM of P4. Submicromolar levels of P4 induced a dose-dependent increase in curvilinear velocity and lateral head displacement, while sperm protein tyrosine phosphorylation was not altered. Macaque spermatozoa exposed to 10 μM of P4 developed fully hyperactivated motility. Similar to human sperm, on approaching cumulus mass and binding to zona pellucida, macaque spermatozoa display hyperactivation and undergo an acrosome reaction that coincides with the rise in the sperm intracellular calcium. Taken together, these data indicate that P4 accelerates the completion of capacitation and provides evidence of spermatozoa "priming" as they move into a gradient of progesterone in search for the oocyte.
Department of Anatomy, Physiology, and Cell Biology, School of Veterinary Medicine, University of California, Davis, California.
Shiho
S
Sumigama
Department of Molecular and Cell Biology, University of California, Berkeley, California.
Steven
S
Mansell
Department of Molecular and Cell Biology, University of California, Berkeley, California.
Melissa
M
Miller
Department of Molecular and Cell Biology, University of California, Berkeley, California.
Polina V
PV
Lishko
Bodega Marine Laboratory, Departments of Environmental Toxicology and Nutrition, University of California, Davis, California.
Gary N
GN
Cherr
Department of Anatomy, Physiology, and Cell Biology, School of Veterinary Medicine, University of California, Davis, California smeyers@ucdavis.edu.
Stuart A
SA
Meyers
Department of Obstetrics and Gynecology, School of Medicine, University of California, Davis, California Center for Health and the Environment, University of California, Davis, California.
Theodore
T
Tollner
D000818:Animals; D002118:Calcium / Q000378:metabolism*; D015220:Calcium Channels / Q000378:metabolism*; D004305:Dose-Response Relationship, Drug; D008253:Macaca mulatta; D008297:Male; D010766:Phosphorylation / Q000187:drug effects; D011374:Progesterone / Q000494:pharmacology*; D011944:Receptors, Androgen / Q000378:metabolism; D013075:Sperm Capacitation / Q000187:drug effects*; D013081:Sperm Motility / Q000187:drug effects; D013094:Spermatozoa / Q000187:drug effects* / Q000378:metabolism; D015044:Zona Pellucida / Q000187:drug effects / Q000378:metabolism
D015220:Calcium Channels; D011944:Receptors, Androgen; D011374:Progesterone; D002118:Calcium
CatSper ion channel; hyperactivation; progesterone; sperm capacitation; zona-induced acrosome reaction