GATA-1 mutation alters the spermatogonial phase and steroidogenesis in adult mouse testis.

Abstract

GATA-1 is a transcription factor from the GATA family, which features zinc fingers for DNA binding. This protein was initially identified as a crucial regulator of blood cell differentiation, but it is currently known that the Gata-1 gene expression is not limited to this system. Although the testis is also a site of significant GATA-1 expression, its role in testicular cells remains considerably unexplored. In the present study, we evaluated the testicular morphophysiology of adult ΔdblGATA mice with a mutation in the GATA-1 protein. Regarding testicular histology, GATA-1 mutant mice exhibited few changes in the seminiferous tubules, particularly in germ cells. A high proportion of differentiated spermatogonia, an increased number of apoptotic pre-leptotene spermatocytes (Caspase-3-positive), and a high frequency of sperm head defects were observed in ΔdblGATA mice. The main differences were observed in the intertubular compartment, as ΔdblGATA mice showed several morphofunctional changes in Leydig cells. Reduced volume, increased number and down-regulation of steroidogenic enzymes were observed in ΔdblGATA Leydig cells. Moreover, the mutant animal showed lower serum testosterone concentration and high LH levels. These results are consistent with the phenotypic and biometric data of mutant mice, i.e., shorter anogenital index and reduced accessory sexual gland weight. In conclusion, our findings suggest that GATA-1 protein is an important factor for germ cell differentiation as well as for the steroidogenic activity in the testis.