Impairment of spermatogenesis in transgenic mice with selective overexpression of Bcl-2 in the somatic cells of the testis

To explore the functional role of Bcl-2 in germ cell development, transgeni c mice carrying 6 kilobases of the inhibin-a promoter were generated to exp ress human bcl-2 gene product in the gonads. Although female transgenic mic e demonstrated decreased follicle apoptosis, enhanced folliculogenesis, and increased germ cell tumorigenesis, the adult males exhibited variable impa irment of spermatogenesis. The degree of damage ranged from tubules with in traepithelial vacuoles of varying sizes to near atrophied tubules consistin g of Sertoli cells and a few spermatogonia. Although there was no significa nt change in body weight, an approximately 34% decrease in testicular weigh ts was noted in transgenic animals compared with wild-type mice. Gamete mat uration, assessed by determining the percentage of tubules with advanced (s teps 13-16) spermatids, was decreased to 44.4% of the values measured in th e wild-type animals. The incidence of germ cell apoptosis increased 3.8-fol d in the transgenic animals and was associated with a marked loss of germ c ells. Electron microscopy of the testes further revealed large vacuoles in the Sertoli cell cytoplasm and dilations of the intracellular spaces betwee n adjacent Sertoli cells, spermatid malformations, and increased germ cell apoptosis in the transgenic animals. There was no evidence of Sertoli cell death either by terminal deoxynucleotidyl transferase-mediated dUTP nick en d labeling (TUNEL) assay or electron microscopy. Leydig cell ultrastructure , cell size and numbers, and plasma levels of testosterone were not differe nt between normal and the transgenic animals. Collectively, these results s upport the critical role of Bcl-2 in male germ cell development and are con sistent with the gender-specific role of the Bcl-2 family members in reprod uction.