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Activin bioactivity affects germ cell differentiation in the postnatal mouse testis in vivo

journal contribution
posted on 2010-05-01, 00:00 authored by S Mithraprabhu, S Mendis, S J Meachem, Laura TubinoLaura Tubino, M M Matzuk, C W Brown, K L Loveland
The transforming growth factor beta superfamily ligand activin A controls juvenile testis growth by stimulating Sertoli cell proliferation. Testicular levels are highest in the first postnatal week, when Sertoli cells are proliferating and spermatogonial stem cells first form. Levels decrease sharply as Sertoli cell proliferation ceases and spermatogenic differentiation begins. We hypothesized that changing activin levels also affect germ cell maturation. We detected an acute and developmentally regulated impact of activin on Kit mRNA in cocultures of Sertoli cells and germ cells from Day 8, but not Day 4, mice. Both stereological and flow cytometry analyses identified an elevated spermatogonium:Sertoli cell ratio in Day 7 testes from Inhba BK/BK mice, which have decreased bioactive activin, and the germ cell markers Sycp3, Dazl, and Ccnd3 were significantly elevated in Inhba BK/BK mice. The flow cytometry measurements demonstrated that surface KIT protein is significantly higher in Day 7 Inhba BK/BK germ cells than in wild-type littermates. By Day 14, the germ cell:Sertoli cell ratio did not differ between genotypes, but the transition of type A spermatogonia into spermatocytes was altered in Inhba BK/BK testes. We conclude that regulated activin signaling not only controls Sertoli cell proliferation, as previously described, but also influences the in vivo progression of germ cell maturation in the juvenile testis at the onset of spermatogenesis. © 2010 by the Society for the Study of Reproduction, Inc.

History

Journal

Biology of Reproduction

Volume

82

Issue

5

Pagination

980 - 990

ISSN

0006-3363

eISSN

1529-7268