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Hum. Reprod. Advance Access published online on April 21, 2006
Human Reproduction, doi:10.1093/humrep/del114
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© The Author 2006. 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
Received February 28, 2006
Accepted March 22, 2006

Article

Protamine 2 precursors, protamine 1/protamine 2 ratio, DNA integrity and other sperm parameters in infertile patients

Nuria Torregrosa 1, David Domínguez-Fandos 1, Maria Isabel Camejo 2, Cynthia R. Shirley 3, Marvin L. Meistrich 3, José Luis Ballescà 4, and Rafael Oliva 1 *

1 Human Genetics Research Group, IDIBAPS, University of Barcelona, Barcelona, Spain and Genetics Service, Hospital Clínic i Provincial, Barcelona, Spain
2 Human Genetics Research Group, IDIBAPS, University of Barcelona, Barcelona, Spain and Genetics Service, Hospital Clínic i Provincial, Barcelona, Spain; Departamento de Biología de Organismos, Universidad Simón Bolívar, Baruta, Venezuela
3 Department of Experimental Radiation Oncology, The University of Texas M. D. Anderson Cancer Center, Houston, TX, USA
4 Institut Clínic de Ginecologia, Obstetricia i Neonatología, Hospital Clínic i Provincial, Barcelona, Spain

* To whom correspondence should be addressed.
Rafael Oliva, E-mail: roliva{at}ub.edu


  Abstract

BACKGROUND: The protamine 1-to-protamine 2 ratio (P1/P2) is altered in the sperm cells of some infertile patients. Also, evidence for increased protamine 2 precursors (pre-P2) in a few patients has been reported. But so far, there have been no studies measuring simultaneously these two variables in a large number of patients. METHODS: We measured the P1/P2 ratio and the presence of pre-P2 using, for the first time, an antibody specific to the precursor pre-P2, together with other sperm parameters in 224 infertile patients. Additionally, the DNA integrity was assessed by terminal transferase dUTP nick-end labelling (TUNEL) in a subset of the samples. RESULTS: Pre-P2 levels show a significant positive correlation with the P1/P2 ratio, with the presence of other proteins and, at low pre-P2 levels, with TUNEL-positive sperm. An inverse correlation with sperm count, normal morphology and motility was detected. CONCLUSIONS: The levels of pre-P2 may provide clues into the pathogenic mechanisms of infertility. The increased proportion of pre-P2 in some patients with increased P1/P2 ratio suggests an involvement of pre-P2 processing. The positive correlation between TUNEL-positive sperm and pre-P2 at low pre-P2/P2 ratios also suggests a link between deficient protamine processing and decreased DNA integrity.

Keywords: DNA integrity/infertility/precursor/protamine/sperm.
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