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Mol. Hum. Reprod. Advance Access originally published online on January 10, 2006
Molecular Human Reproduction 2006 12(1):41-50; doi:10.1093/molehr/gah258
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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

A novel mechanism of protamine expression deregulation highlighted by abnormal protamine transcript retention in infertile human males with sperm protamine deficiency

V.W. Aoki1,2,3, L. Liu1,2 and D.T. Carrell1,2,3,4,5

1Andrology and IVF Laboratories, 2Department of Surgery, 3Department of Physiology and 4Department of Obstetrics and Gynecology, University of Utah School of Medicine, Salt Lake City, UT, USA

5 To whom correspondence should be addressed at: Andrology and IVF Laboratories, University of Utah School of Medicine, 675 Arapeen Dr Ste 205, Salt Lake City, UT 84117, USA. E-mail: douglas.carrell{at}hsc.utah.edu

Sperm protamine deficiency has been associated with human male infertility. However, the aetiology of deregulated protamine expression remains elusive. The objective of this study was to evaluate the underlying aetiology of protamine deficiency in male infertility patients with deregulated protamine expression. Protamine-1 (P1) and protamine-2 (P2) protein concentrations were compared against P1 and P2 mRNA levels in the sperm of 166 male infertility patients and 27 men of known fertility. Protamine protein concentrations were quantified by nuclear protein extraction, gel electrophoresis and densitometry analysis. Semi-quantitative real-time RT–PCR was used to quantify P1 and P2 mRNA levels. P1 mRNA concentrations were significantly increased in patients underexpressing P1 protein versus those with normal and increased P1 levels. In patients with an abnormally low ratio of P1 to P2 (P1/P2 <0.8), there was a significant increase in P1 mRNA retention. Patients underexpressing P2 also had significantly increased mean P2 mRNA levels, although the majority of these P2-deficient patients showed an increased frequency of significantly reduced P2 mRNA levels. This is the first study to concomitantly evaluate P1 and P2 protein and mRNA levels in mature human sperm. Abnormally elevated protamine mRNA retention appears to be associated with aberrant protamine expression in infertile human males. These data suggest that defects in protamine translation regulation may contribute to protamine deficiency in infertile males.

Key words: expression/human/protamines/RT–PCR/sperm


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