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Transcription Factor GATA-6, Cell Proliferation, Apoptosis, and Apoptosis-Related Proteins Bcl-2 and Bax in Human Fetal Testis

Children’s Hospital and Program for Developmental and Reproductive Biology, Biomedicum Helsinki, University of Helsinki (I.K., M.H.), 00014 Helsinki, Finland; Departments of Physiology and Pediatrics, University of Turku (J.T.), 20520 Turku, Finland; Departments of Obstetrics and Gynecology (T.V., J.S.T.) and Pathology (R.H.), University of Oulu, 90220 Oulu, Finland; and Department of Pediatrics, Washington University (M.H.), St. Louis, Missouri 63110

Address all correspondence and requests for reprints to: Markku Heikinheimo, M.D., Ph.D., Biomedicum Helsinki, 5th floor, Room B525b, P.O. Box 63, University of Helsinki, 00014 Helsinki, Finland. E-mail: markku.heikinheimo{at}helsinki.fi.

The GATA family of transcription factors have been implicated in regulating the development and function of many organs. Furthermore, they have been linked to signaling cascades regulating cell fate through apoptosis. GATA-6 has been shown to be expressed in the gonads, but its cell-specific expression in the testis has remained unclear. We have studied GATA-6 expression in human fetal testis using in situ hybridization and immunohistochemistry and compared these results with the expression of the apoptosis-related proteins Bcl-2 and Bax. Furthermore, apoptosis was studied by thymidine deoxyribose-mediated deoxy-UTP nick end labeling assay, and cell proliferation by Ki-67 immunohistochemistry. GATA-6 mRNA and protein were expressed in Sertoli and Leydig cells early in gestation. Apoptotic cells were scanty between wk 16 and 40, and proliferation significantly ceased during the third trimester, supporting the view that only a little tissue remodeling occurs in the late fetal testis. Bax was present throughout the fetal period, whereas Bcl-2 expression decreased toward term. Neither of these factors correlated to the extent of apoptosis, and thus their role in the regulation of apoptosis in the fetal testis remains open. Despite strong expression, GATA-6 did not correlate with apoptosis or cell proliferation and is therefore unlikely to be directly involved in these processes in the human fetal testis.

This work was supported by the Finnish Pediatric Research Foundation, the Finnish Medical Foundation, and the Finnish Cultural Foundation (to I.K.); the Sigrid Jusélius Foundation (to J.S.T., and M.H.); Oulu University Central Hospital (to J.S.T. and T.V.); the Academy of Finland (to J.S.T. and J.T.); the Finnish Research Program on Environmental Health, of the Academy of Finland and Turku University Central Hospital (to J.T.); University Central Hospital in Helsinki (to I.K. and M.H.); and Helsinki University Research Foundation (to I.K.) and Funds (to M.H.).

Abbreviations: TUNEL, Thymidine deoxyribose-mediated deoxy-UTP nick end labeling.

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