Aberrant mRNA expression of chromatin remodelling factors in round spermatid maturation arrest compared with normal human spermatogenesis

Abstract

During human spermiogenesis, chromatin condensation is associated with replacement of histones by protamines. This exchange is supported by acetylated histones and chromatin remodelling factors. Ten chromatin remodelling factor protein families are known. This study aims to analyse whether a different chromatin remodelling factor expression pattern exists between normal spermatogenesis and round spermatid maturation arrest as potential reason for impaired spermatogenesis and idiopathic male infertility. Laser capture microdissection was used to excise seminiferous tubules from testicular biopsies with normal spermatogenesis and round spermatid maturation arrest. RNA was isolated, first strand cDNA synthesis and pre-amplification were performed using Epigenetic Chromatin Remodelling Factors PCR arrays with 84 genes. Applying hierarchical cluster analysis, three gene expression clusters with six subgroups were identified. The expression pattern ranges from a few high expressed genes in round spermatid maturation arrest to a multitude of genes (74) which are more highly expressed in normal spermatogenesis than in maturation arrest. A total of 22 genes showed a significant difference between normal spermatogenesis and round spermatid maturation arrest (1 gene was up-regulated and 21 genes were down-regulated in the developmental arrest). The significantly different expression of chromatin remodelling factors between normal spermatogenesis and round spermatid maturation arrest may lead to impaired epigenetic information and aberrant transcription during sperm development representing one possible reason for developmental arrest of round spermatids.

The tumour suppressor CHD5 forms a NuRD-type chromatin remodelling complex

“…This finding has been confirmed recently by others [51]. In addition, high expression of chromatin remodelling factors, including CHD5, are associated with normal spermatogenesis, whereas decreased expression of these genes is closely associated with round spermatid arrest [52]. …”

CHD5 is required for spermiogenesis and chromatin condensation

“…During spermiogenesis, the condensation of chromatin and the organization of DNA within the nucleus determine the final shape of the nucleus (Hammadeh et al, 1999). Indeed, there are many reports describing the association between disturbances in sperm chromatin condensation, morphology and male infertility (Lin et al, 2011; Sadek et al, 2011; Steilmann et al, 2010; Talebi et al, 2011). …”

“…Chd5 is most abundantly expressed in the nervous system and the testis. In humans, high CHD5 and other chromatin remodeling factors are associated with normal spermatogenesis, whereas decreased expression of these genes closely associated with round spermatid arrest (Steilmann et al, 2010). CHD5 may play different roles in different cell types, and so the suppression of cell growth and facilitating chromatin condensation are only two aspects of this protein’s chromatin-remodeling functions (Saito et al, 2010).…”

Mouse BAZ1A (ACF1) Is Dispensable for Double-Strand Break Repair but Is Essential for Averting Improper Gene Expression during Spermatogenesis

“…Interestingly, human BAZ1A was down-regulated in testis tissue displaying round spermatid maturation arrest, isolated from infertile men with azoospermia [80]. Thus, it is possible that decreased BAZ1A levels may also lead to human male sterility.…”