Hum. Reprod. Advance Access originally published online on January 5, 2007
Human Reproduction 2007 22(4):953-960; doi:10.1093/humrep/del494
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MAGE-A1, GAGE and NY-ESO-1 cancer/testis antigen expression during human gonadal development
1 Medical Biotechnology Center, Institute of Medical Biology, University of Southern Denmark, Odense C, Denmark 2 Departments of Clinical Pathology 3 Oncology, Odense University Hospital, Odense C, Denmark
4 To whom correspondence should be addressed at: Medical Biotechnology Center, Institute of Medical Biology, University of Southern Denmark, Winsloewparken 25, 3., DK-5000 Odense C, Denmark. E-mail: hditzel{at}health.sdu.dk
BACKGROUND: Cancer/testis antigens (CTAs) are expressed in several cancers and during normal adult male germ cell differentiation. Little is known about their role in fetal development of human germ cells.
METHODS: We examined expression of the CTAs MAGE-A1, GAGE and NY-ESO-1 in fetal gonads by single and double immunohistochemical staining.
RESULTS: We found that GAGE was expressed in the primordial germ cells of the gonadal primordium, whereas MAGE-A1 and NY-ESO-1 were first detected in germ cells of both testis and ovary after sexual differentiation was initiated. The number of positive germ cells and the staining intensity of all three CTAs peaked during the second trimester and gradually decreased towards birth in both male and female germ cells. In oocytes, MAGE-A1 expression terminated around birth, whereas NY-ESO-1 expression persisted through the neonatal stage and GAGE expression was maintained until adulthood. The population of GAGE-expressing male and female germ cells partially overlapped the population of OCT4-positive cells, whereas MAGE-A1 and NY-ESO-1 were clearly expressed only by OCT4-negative cells.
CONCLUSIONS: Our results suggest that MAGE-A1 and NY-ESO-1 are associated with highly proliferating germ cells, whereas GAGE proteins have a more general function in germ cells unrelated to any specific developmental stage. The recognition of differential cellular expression of GAGE, MAGE-A1, NY-ESO-1 and OCT4 may help define biologically distinct germ cell subpopulations.
Key words: fetal germ cells/germ cell subpopulations/immunohistochemistry/OCT4/primordial germ cells
Submitted on August 23, 2006; resubmitted on October 24, 2006; accepted on December 1, 2006.
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