Multiple roles of FOXJ3 in spermatogenesis: A lesson from Foxj3 conditional knockout mouse models

Abstract

The transcription factor FOXJ3 (Forkhead box J3) is highly expressed in spermatogonia and meiotic spermatocytes within mouse testes. Here, we addressed how FOXJ3 might participate in spermatogenesis using two conditional knockout mouse models in which Foxj3 was deleted from either spermatogonia or meiotic spermatocytes. Both models exhibited complete male sterility, but distinct etiologies: Deleting FOXJ3 from spermatogonia using Foxj3^flox/flox , Mvh-Cre mice caused Sertoli-cell-only syndrome in males. Foxj3-deficient spermatogonia were lost as early as postnatal Day 4, partially due to the accumulation of DNA double-stranded breaks. In contrast, loss of FOXJ3 in spermatocytes using Foxj3^flox/flox , Stra8-Cre mice led to meiotic arrest. Indeed, the mRNA abundance of meiotic arrest-related proteins (Rad51, Dmc1, Brca1, Brca2, Brit1, Eif4g3, Hop2, Hormad1, and Rnf212) was significantly reduced in Foxj3^flox/flox , Stra8-Cre spermatocytes. Thus, we conclude that FOXJ3 is required for the survival of spermatogonia and participates in spermatocyte meiosis. Mol. Reprod. Dev. 83: 1060-1069, 2016. © 2016 Wiley Periodicals, Inc.