title: Expression of a truncated form of KIT tyrosine kinase in human spermatozoa correlates with sperm DNA integrity.
abstract: BACKGROUND
  TR-KIT, a truncated form of KIT (the KITL receptor), corresponding to the c-terminal half of the intracellular split tyrosine kinase domain, is expressed during the haploid stages of mouse spermatogenesis, and is one of the candidate sperm factors possibly involved in egg activation at fertilization.
  
  
  METHODS
  Immunocytochemistry of adult human testis, and studies of human semen samples from volunteer donors through immunofluorescence, confocal microscopy, flow cytometry, western blot and RT-PCR analyses were performed.
  
  
  RESULTS
  We show that the TR-KIT is expressed during spermiogenesis in the human testis, and that it is maintained in human ejaculated spermatozoa. TR-KIT is localized both in the equatorial segment and in the sub-acrosomal region of the human sperm head. The equatorial localization of the TR-KIT persists after the spontaneous acrosome reaction. Cytometric analysis of several sperm samples from volunteer donors, showed variable degrees of the TR-KIT-specific immunolabeling, and a significant inverse correlation (Pearson's coefficient, r = -0.76, P < 0.0001, n = 23) of the TR-KIT positivity with markers of sperm damage, i.e. DNA fragmentation, as revealed by terminal deoxynucleotidyl transferase-mediated deoxyuridine triphosphate-nick end labeling (TUNEL) analysis and the intense clusterin positivity. We also found less significant inverse correlation with altered head morphology (r = -0.47, P < 0.05, n = 23) and direct correlation with sperm forward motility parameters (r = 0.59, P < 0.01, n = 23).
  
  
  CONCLUSIONS
  The TR-KIT is present in the equatorial region of human spermatozoa, which is the first sperm component entering into the oocyte cytoplasm after fusion with the egg. This localization is consistent with the function previously proposed for this protein in mice. In addition, the TR-KIT represents a potential predictive parameter of human sperm quality.
authors.affiliation: Department of Histology and Medical Embryology, University of Rome La Sapienza, Rome, Italy.
authors.forename: Barbara
authors.initials: B
authors.lastname: Muciaccia
authors.forename: Claudio
authors.initials: C
authors.lastname: Sette
authors.forename: Maria Paola
authors.initials: MP
authors.lastname: Paronetto
authors.forename: Marco
authors.initials: M
authors.lastname: Barchi
authors.forename: Simona
authors.initials: S
authors.lastname: Pensini
authors.forename: Angela
authors.initials: A
authors.lastname: D'Agostino
authors.forename: Loredana
authors.initials: L
authors.lastname: Gandini
authors.forename: Raffaele
authors.initials: R
authors.lastname: Geremia
authors.forename: Mario
authors.initials: M
authors.lastname: Stefanini
authors.forename: Pellegrino
authors.initials: P
authors.lastname: Rossi
mesh_terms: D020101:Acrosome Reaction; D000328:Adult; D000368:Aged; D015415:Biomarkers / Q000378:metabolism; D048430:Cell Shape; D051152:Clusterin / Q000378:metabolism; D053938:DNA Fragmentation; D015870:Gene Expression; D006801:Humans; D008297:Male; D008875:Middle Aged; D009928:Organ Specificity; D020033:Protein Isoforms / Q000378:metabolism; D021381:Protein Transport; D019009:Proto-Oncogene Proteins c-kit / Q000235:genetics / Q000378:metabolism*; D012333:RNA, Messenger; D055101:Semen Analysis; D013077:Sperm Head / Q000378:metabolism / Q000473:pathology; D013094:Spermatozoa / Q000737:chemistry* / Q000378:metabolism* / Q000473:pathology; D013737:Testis / Q000166:cytology / Q000378:metabolism; D055815:Young Adult
chemical_list: D015415:Biomarkers; C495242:CLU protein, human; D051152:Clusterin; D020033:Protein Isoforms; D012333:RNA, Messenger; D019009:Proto-Oncogene Proteins c-kit