Bcl-2 inhibits apoptosis of spermatogonia and growth of spermatogonial stem cells in a cell-intrinsic manner

The growth, differentiation, and death/survival of spermatogonia are precis ely regulated for the proper production of spermatozoa. We have previously shown that Bcl-2 ectopically expressed in spermatogonia caused the inhibiti on of normal spermatogonial apoptosis and the subsequent failure of differe ntiation in transgenic mice. In addition, the growth of spermatogonial stem cells seemed to be temporally arrested in the transgenic mice. In the pres ent study, we attempted to examine whether the abnormality of spermatogonia described above was caused by Bcl-2 misexpression in the spermatogonia or by an abnormal spermatogenic environment of the transgenic mice. We transpl anted testicular cells of transgenic mice to seminiferous tubules of W/W-v mice in which transplanted normal testicular cells can undergo spermatogene sis. We found that the transplanted spermatogonia of the transgenic mice re produced a series of abnormal changes including temporal growth arrest of s permatogonial stem cells and abnormal accumulation of spermatogonia in tubu les, which were also observed in the testes of the transgenic mice. The res ults indicated that Bcl-2 inhibited apoptosis of spermatogonia and growth o f spermatogonial stem cells in a cell-intrinsic manner. We also cultured te sticular cells of transgenic mice and found that the spermatogonia of the t ransgenic mice were better able to survive than were those of wild-type mic e but that their differentiation was not affected. The result suggested tha t failure of differentiation of the accumulated spermatogonia in the transg enic testes is not due to the abnormality of the bcl-2 misexpressing sperma togonia, but may be caused by extrinsic problems including improper interac tion of spermatogonia with supporting cells. (C) 2001 Wiley-Liss, Inc.