CHROMATIN REMODELING IN SPERMATIDS: A SENSITIVE STEP FOR THE GENETIC INTEGRITY OF THE MALE GAMETE

Abstract

Several causes of male infertility remain idiopathic. Recently, the condensed state of the sperm head has been demonstrated as a discriminating parameter for the assessment of male infertility. Altered DNA condensation is associated with an increase in DNA strand breakage so the genetic integrity of the male gamete is threatened. The origin of the DNA strand breaks in unknown. However, transient DNA strand breaks appear in the whole population of elongating spermatids during mid-spermiogenesis steps. Most likely, these transient breaks are required to support the change in DNA topology associated with chromatin remodeling at these steps. Histones hyperacetylation is also coincident with the DNA strand breakage steps. Hyperacetylation of histones may represent a necessary condition for strand breakages to form allowing access to the yet unknown enzymatic activity involved in the removal of DNA supercoils. A better characterization of this enzyme activity at these steps is necessary as this may represent a very sensitive process where altercations in the genetic integrity of the male gamete may arise and persist up to the mature spermatozoa. During the chromatin remodeling in spermatids, the combined DNA-condensing activities provides by the basic transition proteins and protamines may optimize the strand repair process emphasizing the link between altered sperm DNA condensation and DNA fragmentation. The mutagenic potential of these events may have been overlooked as it may result in fertility and/or developmental problems.