Human Reproduction Update Advance Access originally published online on March 31, 2006
Human Reproduction Update 2006 12(4):417-435; doi:10.1093/humupd/dml009
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Protamines and male infertility
Human Genetics Laboratory, Genetics Unit, Department of Ciències Fisiològiques I, Faculty of Medicine, University of Barcelona and Hospital Clínic, Institut d’Investigacions Biomèdiques August Pi i Sunyer (IDIBAPS), Barcelona, Spain
To whom correspondence should be addressed at: Human Genetics Laboratory, Department of Ciencies Fisiològiques I, University of Barcelona, Institut d’Investigacions Biomèdiques August Pi i Sunyer (IDIBAPS), Casanova 143, 08036 Barcelona, Spain. E-mail: roliva{at}ub.edu
Submitted on November 23, 2005; resubmitted on February 8, 2006; accepted on February 15, 2006
Protamines are the major nuclear sperm proteins. The human sperm nucleus contains two types of protamine: protamine 1 (P1) encoded by a single-copy gene and the family of protamine 2 (P2) proteins (P2, P3 and P4), all also encoded by a single gene that is transcribed and translated into a precursor protein. The protamines were discovered more than a century ago, but their function is not yet fully understood. In fact, different hypotheses have been proposed: condensation of the sperm nucleus into a compact hydrodynamic shape, protection of the genetic message delivered by the spermatozoa, involvement in the processes maintaining the integrity and repair of DNA during or after the nucleohistone–nucleoprotamine transition and involvement in the epigenetic imprinting of the spermatozoa. Protamines are also one of the most variable proteins found in nature, with data supporting a positive Darwinian selection. Changes in the expression of P1 and P2 protamines have been found to be associated with infertility in man. Mutations in the protamine genes have also been found in some infertile patients. Transgenic mice defective in the expression of protamines also present several structural defects in the sperm nucleus and have variable degrees of infertility. There is also evidence that altered levels of protamines may result in an increased susceptibility to injury in the spermatozoan DNA causing infertility or poor outcomes in assisted reproduction. The present work reviews the articles published to date on the relationship between protamines and infertility.
Key words: chromatin / genome / mutation / protamine / spermatozoa
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