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 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.
O'Bryan
Moira K
MK
Monash Institute of Medical Research, Monash University, Melbourne, Australia. moira.obryan@med.monash.edu.au
Takada
Shuji
S
Kennedy
Claire L
CL
Scott
Greg
G
Harada
Shun-ichi
S
Ray
Manas K
MK
Dai
Qunsheng
Q
Wilhelm
Dagmar
D
de Kretser
David M
DM
Eddy
E Mitch
EM
Koopman
Peter
P
Mishina
Yuji
Y
D000818:Animals; D004268:DNA-Binding Proteins / Q000172:deficiency / Q000235:genetics / Q000502:physiology*; D005091:Exons; D005298:Fertility / Q000502:physiology*; D017353:Gene Deletion; D005838:Genotype; D008297:Male; D051379:Mice / Q000196:embryology / Q000235:genetics*; D018345:Mice, Knockout; D008822:Mice, Transgenic; D016133:Polymerase Chain Reaction; D015183:Restriction Mapping; D055757:SOXE Transcription Factors; D012708:Sertoli Cells / Q000502:physiology*; D013737:Testis / Q000166:cytology / Q000196:embryology / Q000502:physiology; D014157:Transcription Factors / Q000172:deficiency / Q000235:genetics / Q000502:physiology*
D004268:DNA-Binding Proteins; D055757:SOXE Transcription Factors; C498639:Sox8 protein, mouse; D014157:Transcription Factors