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

Abstract

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.

Differential developmental expression of transcription factors GATA-4 and GATA-6, their cofactor FOG-2 and downstream target genes in testicular carcinoma in situ and germ cell tumors

“…Normal germ cells were negative for GATA-4, except for a heterogeneous staining of acrosomes in subset of spermatids, which was apparently unspecific. GATA-6, FOG-2, SF1, and INHa were mostly negative in germ cells, whereas Sertoli and Leydig cells expressed GATA-6, FOG-2, SF1, and INHa, as described earlier (10,12,17).…”

“…Several GATA-4 target genes are essential in gonadal differentiation steroidogenic factor 1 (SF1, SRY, SOX9) and hormone regulation anti-Mü llerian hormone (AMH, inhibin-a (INH-a)) (3,(5)(6)(7)(8). During fetal testis development, GATA-4 and GATA-6 are expressed in mouse and human Sertoli and Leydig cells (9,10). An essential GATA-4 co-factor, friend of GATA (FOG)-2 is also expressed in murine Sertoli and Leydig cells (11,12), and it is known that FOG-2 interaction is required for proper GATA-4 function in the testis.…”

Bilateral anorchia in infancy: Occurence of micropenis and the effect of testosterone treatment

“…An imbalance between testicular cell proliferation and apoptosis during fetal and newborn periods also needs to be explored. 31,32 A small but otherwise normally shaped penis is seen in various conditions and is mostly related to congenital hypopituitarism or isolated hypothalamic hypogonadism. As in these cases, patients with bilateral anorchia and micropenis require testosterone therapy to increase penis length.…”

Expression of FGFR3 during human testis development and in germ cell-derived tumours of young adults

“…2004; Ketola et al, 2003;Müller and Skakkebaek, 1983;Paniagua and Nistal, 1984), prompting us to look into a possible association between FGFR3 expression and cell proliferation. It turned out harder than expected because of the problem with the two proliferation marker antibodies, which were not compatible with both fixatives used to preserve the human tissues.…”