Apoptosis regulation in the testis: Involvement of Bcl-2 family members

Using immunohistochemical techniques and Western blot analysis, the possibl e role of Bcl-2 family members Bax, Bcl-2, Bct-x(s), and Bcl-x(l) in male g erm cell density-related apoptosis and DNA damage induced apoptosis was stu died. The apoptosis inducer Bax was localized in all mouse and human testic ular cell types, but despite the fact that irradiation induces its transcri ptional activator, p53 in the human, Bax expression did not change after ir radiation. The apoptosis inhibitor Bcl-2 appeared to be present in late spe rmatocytes and spermatids and was up-regulated in these cells after a dose of 4 Gy of X-rays. Finally Bcl-x was expressed in both the mouse and human testis. The apoptosis inhibiting long transcripts of Bcl-x, Bcl-x(l), were expressed in spermatogonia and spermatocytes and were up-regulated after X- irradiation. The apoptosis inducing shorter form of Bcl-x, Bcl-x,, was foun d to be expressed only in somatic cells, like peritubular and Leydig cells. While Bax is important in germ cell density regulation, Bax expression did not change after DNA damage inflicted by X-radiation. Hence, spermatogonia l apoptosis after X-irradiation may not be induced via the apoptosis induce r Bax. Furthermore, as Bcl-x(l), but not Bcl-2, is present in spermatogonia and spermatocytes, Bcl-x(l) may regulate germ cell density, possibly in co operation with Bax. As Bcl-x(l) expression is enhanced after irradiation, t his protein may also have a role in the response of spermatogonia and sperm atocytes to irradiation. Mol. Reprod. Dev. 56:353-359, 2000. (C) 2000 Wiley -Liss, Inc.