Original Article

Virchows Archiv

, Volume 451, Issue 4, pp 805-814

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 MeytsAffiliated withUniversity Department of Growth and Reproduction, Section GR-5064, Rigshospitalet Email author 
  • , S. N. PollAffiliated withUniversity Department of Growth and Reproduction, Section GR-5064, Rigshospitalet
  • , I. GoukasianAffiliated withUniversity Department of Growth and Reproduction, Section GR-5064, Rigshospitalet
  • , C. JeanneauAffiliated withDepartments of Oral Diagnostics and Cellular and Molecular Medicine, University of Copenhagen
  • , A. S. HerlihyAffiliated withUniversity Department of Growth and Reproduction, Section GR-5064, Rigshospitalet
  • , E. P. BennettAffiliated withDepartments of Oral Diagnostics and Cellular and Molecular Medicine, University of Copenhagen
  • , N. E. SkakkebækAffiliated withUniversity Department of Growth and Reproduction, Section GR-5064, Rigshospitalet
  • , H. ClausenAffiliated withDepartments of Oral Diagnostics and Cellular and Molecular Medicine, University of Copenhagen
  • , A. GiwercmanAffiliated withUniversity Department of Growth and Reproduction, Section GR-5064, RigshospitaletFertility Centre and Department of Urology, Malmö University Hospital, Lund University
    • , U. MandelAffiliated withDepartments of Oral Diagnostics and Cellular and Molecular Medicine, University of Copenhagen

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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