Virchows Archiv

, 451:805

Changes in the profile of simple mucin-type O-glycans and polypeptide GalNAc-transferases in human testis and testicular neoplasms are associated with germ cell maturation and tumour differentiation

  • E. Rajpert-De Meyts
  • S. N. Poll
  • I. Goukasian
  • C. Jeanneau
  • A. S. Herlihy
  • E. P. Bennett
  • N. E. Skakkebæk
  • H. Clausen
  • A. Giwercman
  • U. Mandel
Original Article

Abstract

Testicular germ cell tumours (TGCT) exhibit remarkable ability to differentiate into virtually all somatic tissue types. In this study, we investigated changes in mucin-type O-glycosylation, which have been associated with somatic cell differentiation and cancer. Expression profile of simple mucin-type O-glycans (Tn, sialyl-Tn, T), histo-blood group H and A variants and six polypeptide GalNAc-transferases (T1–4, T6, T11) that control the site and density of O-glycosylation were analysed by immunohistochemistry during human testis development and in TGCT. Normal testis showed a restricted pattern; gonocytes expressed abundant sialyl-Tn and sialyl-T, and adult spermatogonia were devoid of any glycans, whereas spermatocytes and spermatids expressed exclusively glycans Tn and T and the GalNAc-T3 isoform. A subset of mature ejaculated spermatozoa expressed an additional glycan sialyl-T. The pattern found in testicular neoplasms recapitulated the developmental order: Pre-invasive carcinoma in situ (CIS) cells and seminoma expressed fetal type sialylated glycans in keeping with their gonocyte-like phenotype. Neither simple mucin-type O-glycans nor GalNAc-transferase isoforms were found in undifferentiated nonseminoma, i.e. embryonal carcinoma, whereas teratomas expressed them all to some extent but in a disorganized manner. We concluded that simple mucin-type O-glycans and their transferases are developmentally regulated in the human testis, with profound changes associated with neoplasia. The restricted O-glycosylation pattern in haploid germ cells suggests a role in their maturation or egg recognition/fertilization warranting further studies in male infertility, whereas the findings in TGCT provide new diagnostic tools and support our hypothesis that testicular cancer is a developmental disease of germ cell differentiation.

Keywords

Testicular neoplasm Glycosyltransferases GalNAc-transferases Mucin-type O-linked glycosylation Carcinoma in situ testis 

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Copyright information

© Springer-Verlag 2007

Authors and Affiliations

  • E. Rajpert-De Meyts
    • 1
  • S. N. Poll
    • 1
  • I. Goukasian
    • 1
  • C. Jeanneau
    • 2
  • A. S. Herlihy
    • 1
  • E. P. Bennett
    • 2
  • N. E. Skakkebæk
    • 1
  • H. Clausen
    • 2
  • A. Giwercman
    • 1
    • 3
  • U. Mandel
    • 2
  1. 1.University Department of Growth and Reproduction, Section GR-5064RigshospitaletCopenhagenDenmark
  2. 2.Departments of Oral Diagnostics and Cellular and Molecular MedicineUniversity of CopenhagenCopenhagenDenmark
  3. 3.Fertility Centre and Department of UrologyMalmö University Hospital, Lund UniversityMalmöSweden

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