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Hum. Reprod. Advance Access published online on May 14, 2009
Human Reproduction, doi:10.1093/humrep/dep178
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© The Author 2009. Published by Oxford University Press on behalf of the European Society of Human Reproduction and Embryology. All rights reserved. For Permissions, please email: journals.permissions@oxfordjournals.org

Interactions between apoptotic signal transduction and capacitation in human spermatozoa

S. Grunewald1, C. Kriegel, T. Baumann, H.-J. Glander and U. Paasch

Department of Dermatology, Training Center of the European Academy of Andrology, University of Leipzig, Ph.-Rosenthal-Str. 23, 04103 Leipzig, Germany

1 Correspondence address. Tel: +49-341-9718740; Fax: +49-341-9718749; E-mail: sonja.grunewald{at}medizin.uni-leipzig.de

BACKGROUND: Capacitation of sperm is a prerequisite for successful fertilization, determined by hyperactivated motility, increased tyrosine phosphorylation (TyrP) and membrane changes. However, the exact molecular mechanism is not fully clarified. The calpain–calmodulin-system is essential for membrane fusion during capacitation. Recently, interactions with caspase (CP) activation, a main feature of apoptotic cells, were postulated. The objective of our study was to examine interactions between apoptosis signalling and the calpain–calmodulin-system during capacitation.

METHODS: Semen samples from 20 healthy donors were incubated in human tubal fluid at 37°C, 5% CO2 for 3 h without additives (control), with 3% BSA (capacitation), 10 µM calpain-inhibitor III, 20 µM CP-1 inhibitor or 20 µM calmodulin-antagonist. Capacitation was monitored by computer assisted sperm motion analyzer, chlortetracycline (CTC)-assay and western blot (TyrP). Activation of caspases and integrity of transmembrane mitochondrial potential (TMP) were evaluated by flow cytometry.

RESULTS: Capacitation, as measured by CTC assay, increased TyrP levels and hyperactivation, resulted in inactivation of CP-9, CP-3 and improved integrity of the TMP. Inhibition of calpain and CP-1 during capacitation reduced the capacitation-related parameters, but did not lead to apoptosis. Inhibition of calmodulin resulted in blocking of capacitation and stimulation of apoptosis.

CONCLUSION: Interaction of the capacitation and apoptosis signalling systems seems to enable the capacitation process by prevention of apoptosis.

Key words: sperm/capacitation/apoptotic signalling/calpain/calmodulin

Submitted on February 14, 2009; resubmitted on April 12, 2009; accepted on April 17, 2009.


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