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Department of Obstetrics & Gynecology, Center for Research on Reproduction & Women's Health,5 and Center for Clinical Epidemiology and Biostatistics,6 University of Pennsylvania, Philadelphia, Pennsylvania 19104
ABSTRACT
Extracellular adenosine 5'-triphosphate (ATPe) treatment of human sperm has been implicated in improving in vitro fertilization (IVF) results. We used the mouse model to investigate mechanisms of action of ATPe on sperm. ATPe treatment significantly enhanced IVF success as indicated by both rate of pronuclear formation and percentage cleavage to the 2-cell stage. However, ATPe did not increase the percentage of sperm undergoing spontaneous acrosomal exocytosis nor change the pattern of protein tyrosine phosphorylation normally observed in capacitated sperm. ATPe altered sperm motility parameters; in particular, both noncapacitated and capacitated sperm swam faster and straighter. The percentage of hyperactivated sperm did not increase in capacitated ATPe-treated sperm compared to control sperm. ATPe induced a rapid increase in the level of intracellular calcium that was inhibited by two distinct P2 purinergic receptor inhibitors, confirming that these receptors have an ionotropic role in sperm function. The observed motility changes likely explain, in part, the improved fertilizing capability when ATPe-treated sperm were used in IVF procedures and suggest a mechanism by which ATPe treatment may be beneficial for artificial reproductive techniques.
acrosomal exocytosis, acrosome reaction, assisted reproductive technology, extracellular ATP, fertilization, hyperactivation, intracellular calcium, purinergic receptor, sperm motility and transport
3These authors contributed equally to this work.
4These authors were coprincipal investigators of this work.
1Supported by a grant from Duska Scientific Co. to S.B.M. and C.J.W.; the authors do not have any financial interests in this company. G.L.G. was supported by NIH grant HD41552. E.R.-M. and M.G.B were supported by the International Training and Research Program in Population and Health (D43-TW00671).
Correspondence: 2Carmen J. Williams, National Institute of Environmental Health Sciences, P.O. Box 12233, MD E4-05, Research Triangle Park, NC 27709. FAX: 919 541 0696; e-mail: williamsc5{at}niehs.nih.gov
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