title: Spermatogenesis arrest caused by conditional deletion of Hsp90α in adult mice.
abstract: It is controversial whether a functional androgen receptor (AR) on germ cells, including spermatogonia, is essential for their development into sperm and, thus, initiation and maintenance of spermatogenesis. It was recently shown that many spermatocytes underwent apoptosis in the testes of Hsp90α KO mice. We had generated Hsp90α KO mice independently and confirmed this phenotype. However, the important question of whether Hsp90α is required to maintain spermatogenesis in adult mice in which testicular maturation is already completed could not be addressed using these conventional KO mice. To answer this question, we generated a tamoxifen-inducible deletion mutant of Hsp90α and found that conditional deletion of Hsp90α in adult mice caused even more severe apoptosis in germ cells beyond the pachytene stage, leading to complete arrest of spermatogenesis and testicular atrophy. Importantly, immunohistochemical analysis revealed that AR expression in WT testis was more evident in spermatogonia than in spermatocytes, whereas its expression was aberrant and ectopic in Hsp90α KO testis, raising the possibility that an AR abnormality in primordial germ cells is involved in spermatogenesis arrest in the Hsp90α KO mice. Our results suggest that the AR, specifically chaperoned by Hsp90α in spermatogonia, is critical for maintenance of established spermatogenesis and for survival of spermatocytes in adult testis, in addition to setting the first wave of spermatogenesis before puberty.
authors.affiliation: Laboratories for Immunochaperones, Research Center for Allergy and Immunology (RCAI), RIKEN Yokohama Institute ,  Yokohama 230-0045 ,  Japan.
authors.forename: Chiaki
authors.initials: C
authors.lastname: Kajiwara
authors.forename: Shiho
authors.initials: S
authors.lastname: Kondo
authors.forename: Shizuha
authors.initials: S
authors.lastname: Uda
authors.forename: Lei
authors.initials: L
authors.lastname: Dai
authors.forename: Tomoko
authors.initials: T
authors.lastname: Ichiyanagi
authors.forename: Tomoki
authors.initials: T
authors.lastname: Chiba
authors.forename: Satoshi
authors.initials: S
authors.lastname: Ishido
authors.forename: Takehiko
authors.initials: T
authors.lastname: Koji
authors.forename: Heiichiro
authors.initials: H
authors.lastname: Udono