Involvement of A1 adenosine receptors in the acquisition of fertilizing capacity.
Ejaculated mammalian spermatozoa acquire competence to fertilize oocytes by a two-step process: capacitation followed by acrosome reaction. The biochemical and biophysical modifications occurring in vivo in the female reproductive tract can be reproduced in vitro, and previous studies have suggested a capacitative role for adenosine A(1) receptor (A(1)R). Mice with a targeted disruption of the Adora 1 gene (A(1)R-/- mice) provide a useful model for better understanding the role of the A(1)R in fertility. Murine spermatozoa express A(1)R in the head, neck, midpiece region, and tail. The number of capacitated spermatozoa incubated in human tubal fluid was significantly reduced in A(1)R-/- compared with A(1)R+/+ and A(1)R+/- spermatozoa. The difference between A(1) R+/+ and A(1)R-/- mouse spermatozoa was mainly in the time necessary to reach the maximum percentage of capacitation. A(1)R+/+ murine sperm obtained the full state of capacitation within 90 minutes whereas A(1)R-/- sperm required 240 minutes. Caffeine, a known antagonist of A(1) and A(2A) adenosine receptors, lowered the number of capacitated sperm and affected the time of capacitation in a dose-dependent manner, mimicking the effects of the lack of A(1) receptors. Although number, motility, and viability of A(1)R-/- murine sperm was not significantly different from A(1)R+/+ mouse spermatozoa, a significant reduction of the number of pups produced by A(1)R-/- male mice suggests that A(1) receptors must be fully operative to accomplish the optimal degree of capacitation and thereby fertilization.
Minelli
Alba
A
Dipartimento di Scienze Biochimiche e Biotecnologie Molecolari, Sezione Biochimica Cellulare, Perugia, Italy.
Liguori
Lavinia
L
Bellazza
Ilaria
I
Mannucci
Roberta
R
Johansson
Björn
B
Fredholm
Bertil B
BB
D000818:Animals; D002110:Caffeine / Q000494:pharmacology; D002470:Cell Survival / Q000502:physiology; D004305:Dose-Response Relationship, Drug; D005298:Fertility / Q000502:physiology*; D005455:Fluorescent Antibody Technique; D006801:Humans; D008297:Male; D051379:Mice; D018345:Mice, Knockout; D010726:Phosphodiesterase Inhibitors / Q000494:pharmacology; D043682:Receptor, Adenosine A1 / Q000502:physiology*; D013075:Sperm Capacitation / Q000187:drug effects / Q000502:physiology*; D013076:Sperm Count; D013081:Sperm Motility / Q000235:genetics
D010726:Phosphodiesterase Inhibitors; D043682:Receptor, Adenosine A1; D002110:Caffeine