Journal of Andrology, Vol. 25, No. 2, March/April 2004
Copyright © American Society of Andrology
Involvement of A1 Adenosine Receptors in the Acquisition of Fertilizing Capacity
ALBA MINELLI*,
LAVINIA LIGUORI*,
ILARIA BELLAZZA*,
ROBERTA MANNUCCI
,
BJöRN JOHANSSON
AND
BERTIL B. FREDHOLM
From the * Dipartimento di Scienze Biochimiche e
Biotecnologie Molecolari, Sezione Biochimica Cellulare, Perugia, Italy;
Dipartimento di Medicina Interna e Scienze
Oncologiche, Policlinico Monteluce Perugia, Italy; and
Department of Physiology and Pharmacology,
Section of Molecular Neuropharmacology, Karolinska Institutet, Stockholm,
Sweden.
|
Correspondence to: Dr Alba Minelli, Dipartimento Scienze Biochimiche e
Biotecnologie Molecolari, Sezione Biochimica Cellulare, Via del Giochetto,
06123 Perugia, Italy. |
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 A1 receptor
(A1R). Mice with a targeted disruption of the Adora 1 gene
(A1R/ mice) provide a useful model for better
understanding the role of the A1R in fertility. Murine spermatozoa
express A1R in the head, neck, midpiece region, and tail. The
number of capacitated spermatozoa incubated in human tubal fluid was
significantly reduced in A1R/ compared with
A1R+/+ and A1R+/ spermatozoa. The difference
between A1 R+/+ and A1R/ mouse spermatozoa
was mainly in the time necessary to reach the maximum percentage of
capacitation. A1R+/+ murine sperm obtained the full state of
capacitation within 90 minutes whereas A1R/ sperm
required 240 minutes. Caffeine, a known antagonist of A1 and
A2A 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 A1 receptors. Although number, motility,
and viability of A1R/ murine sperm was not
significantly different from A1R+/+ mouse spermatozoa, a
significant reduction of the number of pups produced by
A1R/ male mice suggests that A1 receptors
must be fully operative to accomplish the optimal degree of capacitation and
thereby fertilization.
Key words: A1 adenosine receptors KO mice, A1 adenosine receptors mouse sperm localization, capacitation, caffeine, fertility
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Copyright © 2004 by The American Society of Andrology.