Essential requirement for both hsf1 and hsf2 transcriptional activity in spermatogenesis and male fertility.
Heat shock factors (Hsfs) are major transactivators of heat shock proteins but are also involved in regulation of other genes active in embryonic development. High expression levels of Hsfs in mouse testis during development suggest a role for these factors in spermatogenesis, a cyclic process of spermatogonia cell-differentiation into mature spermatozoa. In contrast to hsf1(-/-) mice, which exhibit normal spermatogenesis, targeted disruption of hsf2 results in reduced testicular size but only a small impairment in male fertility. We show here that disruption of both hsf1 and hsf2 results in a more severe phenotype associated with male sterility due to severe defects in spermatogenesis. Earliest defects observed are the reduced number of germ cells in juvenile mice and germ cells that enter the meiotic prophase fail to progress beyond the pachytene stage. This was associated with a reduction or absence of transcription of genes critically involved in spermatogenesis. The findings suggest that additive or synergistic transcriptional activity of both hsf1 and hsf2 is required for normal mammalian spermatogenesis and male fertility.
Institute of Molecular Medicine and Genetics, Medical College of Georgia, Augusta, Georgia.
Guanghu
G
Wang
Zhekang
Z
Ying
Xiongjie
X
Jin
Naxin
N
Tu
Yan
Y
Zhang
Michele
M
Phillips
Demetrius
D
Moskophidis
Nahid F
NF
Mivechi
D000818:Animals; D017931:DNA Primers; D004268:DNA-Binding Proteins / Q000378:metabolism*; D005298:Fertility / Q000235:genetics*; D005434:Flow Cytometry; D015870:Gene Expression; D020868:Gene Silencing; D005838:Genotype; D000076249:Heat Shock Transcription Factors; D006360:Heat-Shock Proteins / Q000378:metabolism*; D006652:Histological Techniques; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D008854:Microscopy, Electron; D020411:Oligonucleotide Array Sequence Analysis; D013091:Spermatogenesis / Q000235:genetics*; D013094:Spermatozoa / Q000473:pathology; D013737:Testis / Q000378:metabolism / Q000648:ultrastructure; D014157:Transcription Factors / Q000378:metabolism*
D017931:DNA Primers; D004268:DNA-Binding Proteins; D000076249:Heat Shock Transcription Factors; D006360:Heat-Shock Proteins; C490017:Hsf1 protein, mouse; D014157:Transcription Factors; C070389:HSF2 protein, human