Excess type I interferon signaling in the mouse seminiferous tubules leads to germ cell loss and sterility. - Université de Rennes Accéder directement au contenu
Article Dans Une Revue Journal of Biological Chemistry Année : 2011

Excess type I interferon signaling in the mouse seminiferous tubules leads to germ cell loss and sterility.

Résumé

Type I (α and β) interferons (IFNs) elicit antiproliferative and antiviral activities via the surface receptor IFNAR. Serendipitous observations in transgenic mice in 1988 strongly suggested that IFNα/β overexpression in the testis disrupts spermatogenesis. Here, we compare a new mouse strain transgenic for IFNβ (Tg10) and a sister strain lacking the IFNAR1 subunit of IFNAR (Tg10-Ifnar1(-/-)), both strains expressing the transgene in the testis. The main source of IFNβ RNA was the spermatid population. Importantly, the Tg10 mice, but not the double mutant Tg10-Ifnar1(-/-), showed altered spermatogenesis. The first IFNAR-dependent histological alteration was a higher apoptosis index in all germ cell categories apart from non-dividing spermatogonia. This occurred 3 weeks after the onset of IFNβ production at postnatal day 20 and in the absence of somatic cell defects in terms of cell number, expression of specific cell markers, and hormonal activities. Several known interferon-stimulated genes were up-regulated in Tg10 Sertoli cells and prepachytene germ cells but not in pachytene spermatocytes and spermatids. In concordance with this, pachytene spermatocytes and spermatids isolated from wild-type testes did not display measurable amounts of IFNAR1 and phosphorylated STAT1 upon IFNβ challenge in vitro, suggesting hyporesponsiveness of these cell types to IFN. At day 60, Tg10 males were sterile, and Sertoli cells showed increased amounts of anti-Mullerian hormone and decreased production of inhibin B, both probably attributable to the massive germ cell loss. Type I interferon signaling may lead to idiopathic infertilities by affecting the interplay between germ cells and Sertoli cells.

Dates et versions

hal-00682893 , version 1 (27-03-2012)

Identifiants

Citer

Anne-Pascale Satie, Severine Mazaud-Guittot, Isabelle Seif, Dominique Mahé, Zhiguo He, et al.. Excess type I interferon signaling in the mouse seminiferous tubules leads to germ cell loss and sterility.. Journal of Biological Chemistry, 2011, 286 (26), pp.23280-95. ⟨10.1074/jbc.M111.229120⟩. ⟨hal-00682893⟩
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