Human Reproduction Update Advance Access originally published online on January 5, 2007
Human Reproduction Update 2007 13(3):313-327; doi:10.1093/humupd/dml057
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Altered protamine expression and diminished spermatogenesis: what is the link?
1 Andrology and IVF Laboratories, Department of Surgery 2 Department of Physiology 3 Department of Obstetrics and Gynecology, University of Utah School of Medicine, Salt Lake City, UT, USA
4 To whom correspondence should be addressed at: Andrology and IVF Laboratories, 675 S. Arapeen Dr, Suite #205, Salt Lake City, UT 84108, USA. E-mail: douglas.carrell{at}hsc.utah.edu
During the elongating spermatid stage of spermiogenesis, human sperm chromatin undergoes a complex transition in which histones are extensively replaced by protamines in a carefully regulated transition including histone modifications and intermediate and temporary replacement of the histones by sperm-specific transition proteins. The replacement of most histones by protamines 1 and 2 facilitates a high order of chromatin packaging necessary for normal sperm function and may also be necessary for DNA silencing and imprinting changes within the sperm cell. Protamines 1 and 2 are usually expressed in nearly equal quantities, but elevated or diminished protamine 1/protamine 2 ratios are observed in some infertile men and is often associated with severe spermatogenesis defects. Human and animal studies demonstrate that expression of the protamine proteins is uniquely regulated by transcription/translation factors, including storage of the mRNA in ribonucleoprotein (RNP) particles composed of the mRNA, transcription factors and a kinesin molecule necessary for transport of the RNP to the cytoplasm and removal of transcriptional activators from the nucleus. Recent studies indicate that most patients with abnormal protamine protein levels have elevated levels of protamine transcript in the mature sperm cell, indicating a possible defect in transcription or translation. The regulation of protamine expression is unique and includes several possible mechanisms which may be responsible for dysregulation of protamine expression and concurrent broad spectrum defects in spermatogenesis. We suggest two hypotheses: (i) that abnormal protamine expression is indicative of a generalized defect in mRNA storage and/or translation which affects other mRNA transcripts or (ii) that protamines may act as a checkpoint of spermatogenesis.
Key words: chromatin / gene expression / protamine / spermatogenesis / transition protein
Received on September 15, 2006; revised October 20, 2006; accepted on November 7, 2006
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