TY - JOUR
T1 - CHD5 is required for spermiogenesis and chromatin condensation
AU - Zhuang, Tiangang
AU - Hess, Rex A.
AU - Kolla, Venkatadri
AU - Higashi, Mayumi
AU - Raabe, Tobias D.
AU - Brodeur, Garrett M.
N1 - Funding Information:
We thank Drs. Lei Ying, Satoru Otsuru and Ted J. Hofmann (CHOP), for helpful discussions and experiment protocols. We thank Dr. Biao Zhu for EM assistance, as well as Daniel Martinez, Socrates Agrio and Neena Panackal (Pathology Core, CHOP) for assistance in preparing testis sections. We thank Dr. Armore P. Fernando for reading the manuscript. This research was supported by grants from the National Cancer Institute (R01-CA039771), Alex’s Lemonade Stand Foundation, and the Audrey Evans Endowed Chair (GMB). Appendix A
PY - 2014/2
Y1 - 2014/2
N2 - 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.
AB - 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.
KW - CHD5
KW - Chromatin condensation
KW - Histone modification
KW - Infertility
KW - Spermatogenesis
KW - Spermiogenesis
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U2 - 10.1016/j.mod.2013.10.005
DO - 10.1016/j.mod.2013.10.005
M3 - Article
C2 - 24252660
AN - SCOPUS:84892372838
SN - 0925-4773
VL - 131
SP - 35
EP - 46
JO - Mechanisms of Development
JF - Mechanisms of Development
IS - 1
ER -