Human Reproduction, Vol 13, 1248-1254, Copyright © 1998 by Oxford University Press
JD Fisch, B Behr and M Conti
Inhibition of sperm phosphodiesterase (PDE) has been shown to increase cAMP
concentrations and stimulate motility and the acrosome reaction. While
several PDE genes exist in mammals, little is known about the physiological
role of PDE forms expressed in human spermatozoa. Using type-selective
inhibitors, we identified two of the PDE forms expressed in human
spermatozoa and studied their involvement in sperm function. Selective
inhibitors of calcium-calmodulin-regulated PDE1 (8-methoxy-
isobutyl-methylxanthine) and cAMP-specific PDE4 (RS-25344, Rolipram) were
used to study PDE forms in human sperm extracts. 8-MeIBMX and
Rolipram/RS-25344 inhibited sperm PDE activity by 35-40 and 25-30%
respectively. Subcellular fractionation of the sperm homogenate suggests
these pharmacologically distinct forms may be located in separate cellular
regions. To evaluate the functional significance of different PDE forms,
the effect of type-specific PDE inhibition on sperm motility and the
acrosome reaction was examined. PDE4 inhibitors enhanced sperm motility
over controls without affecting the acrosome reaction, while PDE1
inhibitors selectively stimulated the acrosome reaction. These data
indicate at least two distinct PDE types exist in human spermatozoa. Our
findings also support the hypothesis that PDE subtypes affect sperm
function by regulating separate pools of cAMP and may ultimately offer
novel treatments to infertile couples with abnormal semen parameters.
ARTICLES
Enhancement of motility and acrosome reaction in human spermatozoa: differential activation by type-specific phosphodiesterase inhibitors
Division of Reproductive Endocrinology and Infertility, Department of Gynecology and Obstetrics, Stanford University School of Medicine, CA 94305, USA.
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