CHD5 is required for spermiogenesis and chromatin condensation

Abstract

Haploid spermatids undergo extensive cellular, molecular and morphological changes to form spermatozoa during spermiogenesis. Abnormalities in these steps can lead to serious male fertility problems, from oligospermia to complete azoospermia. CHD5 is a chromatin-remodeling nuclear protein expressed almost exclusively in the brain and testis. Male Chd5 knockout (KO) mice have deregulated spermatogenesis, characterized by immature sloughing of spermatids, spermiation failure, disorganization of the spermatogenic cycle and abnormal head morphology in elongating spermatids. This results in the inappropriate placement and juxtaposition of germ cell types within the epithelium. Sperm that did enter the epididymis displayed irregular shaped sperm heads, and retained cytoplasmic components. These sperm also stained positively for acidic aniline, indicating improper removal of histones and lack of proper chromatin condensation. Electron microscopy showed that spermatids in the seminiferous tubules of Chd5 KO mice have extensive nuclear deformation, with irregular shaped heads of elongated spermatids, and lack the progression of chromatin condensation in an anterior-to-posterior direction. However, the mRNA expression levels of other important genes controlling spermatogenesis were not affected. Chd5 KO mice also showed decreased H4 hyperacetylation beginning at stage IX, step 9, which is vital for the histone-transition protein replacement in spermiogenesis. Our data indicate that CHD5 is required for normal spermiogenesis, especially for spermatid chromatin condensation.

Sperm head shaping in ratites: New insights, yet more questions

“…In late phase II spermatids, the condensing chromatin, excluding the contents of the nuclear rostrum beneath the developing acrosome (see below), begins to shrink away from the surrounding nuclear envelope. This process is most conspicuous immediately beneath the forming nuclear rostrum, possibly indicating that chromatin condensation occurs in an anterior-posterior direction as reported, with the exception of man, in mammalian sperm (Dadounne, 1995;Zhuang et al, 2014). As noted above, compaction and shrinkage of the chromatin only occurs well after the appearance of the CM and initial elongation of the nucleus.…”

“…This would appear to indicate that the rostral concentration of microtubules is instrumental in re-modelling that part of the nucleus, in contrast to the caudal part which remains rounded. However, the anterior-posterior gradient observed during the chromatin condensation process in some species (Zhuang et al, 2014) may also account for this phenomenon (see below). The spatial arrangement and extent of the two sets of manchette microtubules would further seem to indicate a role for the CM in head shaping in ratites.…”

“…A correlation has been demonstrated between aberrant chromatin condensation and sperm head shape. In man, for example, a high percentage of abnormally elongated heads display altered chromatin compaction (Prisant et al, 2007), whereas CHD5 (a chromatin remodeling nuclear protein) -deficient mice display abnormal head morphology in elongating spermatids and epididymal spermatozoa (Zhuang et al, 2014). Moreover, in some animal species condensation of the chromatin occurs without the presence of a manchette (Phillips and Asa, 1989).…”

“…Formation and shaping of the sperm head has been studied in numerous vertebrate and invertebrate species (Fawcett et al, 1971;Phillips, 1974;Toshimori and Ito, 2003), particularly in mammals, and a link established between defective head formation / structure and compromised fertility (Barth and Oko, 1989;Dadoune, 1995Dadoune, , 2003Zamboni, 1987;Zhuang et al, 2014). Although conflicting evidence has been presented in the literature, morphological data supplied by conventional transmission electron microscopy, supplemented by the use of animal models, have implicated various cellular components and processes in nuclear (head) morphogenesis (Fawcett, et al, 1971;Hermo et al, 2010;Kierszenbaum et al, 2003Kierszenbaum et al, , 2004Kierszenbaum et al, , 2007Meistrich, 1993).…”

“…Although conflicting evidence has been presented in the literature, morphological data supplied by conventional transmission electron microscopy, supplemented by the use of animal models, have implicated various cellular components and processes in nuclear (head) morphogenesis (Fawcett, et al, 1971;Hermo et al, 2010;Kierszenbaum et al, 2003Kierszenbaum et al, , 2004Kierszenbaum et al, , 2007Meistrich, 1993). These include the role of the forming acrosome ( Kierszenbaum et al, 2003( Kierszenbaum et al, , 2004( Kierszenbaum et al, , 2007Russell et al, 1991) inherent properties of the chromatin condensation process (Fawcett et al, 1971;Prisant et al, 2007;Nozawa et al, 2014;Zhuang et al, 2014) and the involvement of the manchette microtubules (Kierszenbaum, 2002;Meistrich, 1993;Meistrich et al, 1990;Nozawa et al, 2014;Russell et al, 1991Russell et al, , 1994Toshimori and Ito, 2003). In addition, it has been proposed that the ectoplasmic specializations of the Sertoli cells surrounding the sperm head are instrumental in effecting remodeling of the spermatid nucleus (Kierszenbaum et al, 2007;Russell et al, 1994).…”