Sox8 is a critical regulator of adult Sertoli cell function and male fertility

Sox8 encodes a high-mobility group transcription factor that is widely expressed during development. Sox8, -9 and -10 form group E of the Sox gene family which has been implicated in several human developmental disorders. In contrast to other SoxE genes, the role of Sox8 is unclear and Sox8 mouse mu...

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Bibliographic Details
Published in:Developmental biology 2008-04, Vol.316 (2), p.359-370
Main Authors: O'Bryan, Moira K., Takada, Shuji, Kennedy, Claire L., Scott, Greg, Harada, Shun-ichi, Ray, Manas K., Dai, Qunsheng, Wilhelm, Dagmar, de Kretser, David M., Eddy, E. Mitch, Koopman, Peter, Mishina, Yuji
Format: Article
Language:English
Subjects:
Adhesion
Animals
DNA-Binding Proteins - deficiency
DNA-Binding Proteins - genetics
DNA-Binding Proteins - physiology
Exons
Fertility
Fertility - physiology
Gene Deletion
Genotype
Male
Mice - embryology
Mice - genetics
Mice, Knockout
Mice, Transgenic
Polymerase Chain Reaction
Restriction Mapping
Sertoli Cells - physiology
Sox
SOXE Transcription Factors
Sperm
Spermatogenesis
Testis
Testis - cytology
Testis - embryology
Testis - physiology
Transcription Factors - deficiency
Transcription Factors - genetics
Transcription Factors - physiology
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Summary:Sox8 encodes a high-mobility group transcription factor that is widely expressed during development. Sox8, -9 and -10 form group E of the Sox gene family which has been implicated in several human developmental disorders. In contrast to other SoxE genes, the role of Sox8 is unclear and Sox8 mouse mutants reportedly showed only idiopathic weight loss and reduced bone density. The careful analysis of our Sox8 null mice, however, revealed a progressive male infertility phenotype. Sox8 null males only sporadically produced litters of reduced size at young ages. We have shown that SOX8 protein is a product of adult Sertoli cells and its elimination results in an age-dependent deregulation of spermatogenesis, characterized by sloughing of spermatocytes and round spermatids, spermiation failure and a progressive disorganization of the spermatogenic cycle, which resulted in the inappropriate placement and juxtaposition of germ cell types within the epithelium. Those sperm that did enter the epididymides displayed abnormal motility. These data show that SOX8 is a critical regulator of adult Sertoli cell function and is required for both its cytoarchitectural and paracrine interactions with germ cells.
ISSN:0012-1606
1095-564X
DOI:10.1016/j.ydbio.2008.01.042