Isoform-specific expression of hypoxia-inducible factor-1alpha during the late stages of mouse spermiogenesis.
The heterodimeric hypoxia-inducible factor (HIF)-1 is a transcriptional master regulator of several genes involved in mammalian oxygen homeostasis, including erythropoietin, vascular endothelial growth factor, and factors involved in glucose transport and metabolism. The mouse Hif1a gene is expressed from two distinct promoter/first exon combinations resulting in tissue-specific (mHIF-1alphaI.1) and ubiquitous (mHIF-1alphaI.2) mRNA isoforms. By in situ hybridization, we detected mHIF-1alphaI.1 mRNA exclusively in the elongated spermatids of the testis. In vitro studies indicated that the switch from mHIF-1alphaI.2 to mHIF-1alphaI.1 mRNA expression does not occur at the premeiotic stages of mouse spermatogenesis. Exposure of mice to hypoxic conditions induced mHIF-1alphaI.2 protein in spermatocytes and probably in Sertoli cells but not in spermatogonia. In contrast, expression of the putative mHIF-1alphaI.1 protein in spermatozoa of the testis and epididymis was oxygen independent and located to the midpiece of the spermatozoal flagellum. Both the switch in transcript expression during spermiogenesis and the unexpected protein localization in mature sperm cells suggest a so far unrecognized function of HIF-1alpha.
Marti
Hugo H
HH
Max-Planck-Institute for Physiological and Clinical Research, Department of Molecular Cell Biology, D-61231 Bad Nauheim, Germany.
Katschinski
Dörthe M
DM
Wagner
Klaus F
KF
Schäffer
Leonhard
L
Stier
Bettina
B
Wenger
Roland H
RH
D000818:Animals; D002460:Cell Line; D004268:DNA-Binding Proteins / Q000235:genetics / Q000378:metabolism*; D018507:Gene Expression Regulation, Developmental; D000860:Hypoxia / Q000378:metabolism; D051793:Hypoxia-Inducible Factor 1; D051795:Hypoxia-Inducible Factor 1, alpha Subunit; D007150:Immunohistochemistry; D017403:In Situ Hybridization; D007985:Leydig Cells / Q000378:metabolism; D008297:Male; D008540:Meiosis; D051379:Mice; D009687:Nuclear Proteins / Q000235:genetics / Q000378:metabolism*; D009928:Organ Specificity; D010100:Oxygen / Q000378:metabolism; D020033:Protein Isoforms / Q000235:genetics / Q000378:metabolism; D021381:Protein Transport; D012333:RNA, Messenger / Q000235:genetics / Q000378:metabolism; D020133:Reverse Transcriptase Polymerase Chain Reaction; D012708:Sertoli Cells / Q000378:metabolism; D013082:Sperm Tail / Q000378:metabolism; D013087:Spermatids / Q000378:metabolism; D013091:Spermatogenesis / Q000235:genetics*; D013737:Testis / Q000166:cytology / Q000378:metabolism; D014157:Transcription Factors
D004268:DNA-Binding Proteins; C497443:Hif1a protein, mouse; D051793:Hypoxia-Inducible Factor 1; D051795:Hypoxia-Inducible Factor 1, alpha Subunit; D009687:Nuclear Proteins; D020033:Protein Isoforms; D012333:RNA, Messenger; D014157:Transcription Factors; D010100:Oxygen