Disruption of germ cell-Sertoli cell interactions leads to spermatogenic defects.

In the aging human testis, partially regressed tubules contain Sertoli cells with an altered appearance and reduced numbers of germ cells. Investigating the effects of aging on Sertoli cell-germ cell interactions from Brown Norway rats, we have found that a selective breakdown in germ cell-Sertoli interactions could lead to severe reductions in male fertility. Previous studies have identified two specific inducible germ cell markers (a von Ebner's-like protein and the Huntington disease protein) and two specific inducible Sertoli cell markers (a sertonin receptor and a novel gene) that are expressed in Sertoli cell-germ cell cocultures and in vivo [Endocrinology 140 (1999a) 5754; J. Biol. Chem. 27 (1999b) 10737]. We find that germ cells from aged regressed testes are unable to respond to selective signals from Sertoli cells, although germ cells from aged normal sized testes respond well. Similarly, Sertoli cells from aged regressed testes fail to respond to certain signals from young germ cells. We propose that selective disruptions in communication between Sertoli cells and germ cells contribute to germ cell loss during aging.