Novel androgen-induced activity of an antimicrobial beta-defensin: Regulation of Wolffian duct morphogenesis

The Wolffian duct (WD) undergoes morphological changes induced by androgens to form the epididymis, which is an organ essential for sperm maturation. Androgen action in WD epithelium involves paracrine factors of mesenchymal origin that function by still poorly understood mechanisms. Here we studied the antimicrobial beta-defensin SPAGIIC as a new player in duct morphogenesis, localized prenatally in the WD mesenchyme. Organotypic culture of rat WDs and tissues from Androgen Receptor (AR) knockout mice (ARKO) were used. Our results show that androgen/AR signaling differentially regulated SPAGIIC expression at mRNA and protein levels in the developing WD. WDs incubated with recombinant human SPAGI1C were shorter and less coiled as a result of reduced epithelial cell proliferation, but not increased apoptosis. Our results suggested beta-defensin SPAGIIC as an androgen-target required for WD morphogenesis. This highlights the multifunctional repertoire of the beta-defensin protein family and their potential contribution to the in utero environment that determines male reproductive success. (C) 2016 Elsevier Ireland Ltd. All rights reserved.Conselho Nacional de Desenvolvimento Cientifico e TecnologicoSao Paulo Research Foundation (FAPESP)Coordenacao de Aperfeicoamento de Pessoal de Nivel Superior (CAPES fellowship)National Institutes of Health Eunice Kennedy Shriver NICHD (NIH)UK MRCUniv Fed Sao Paulo, Escola Paulista Medicina, Dept Pharmacol, Sect Expt Endocrinol, Rua 03 maio 100,INFAR,Vila Clementino, BR-04044020 Sao Paulo, SP, BrazilUniv Edinburgh, MRC Ctr Reprod Hlth, Queens Med Res Inst, Edinburgh, Midlothian, ScotlandUniv Virginia, Sch Med, Dept Cell Biol, Charlottesville, VA USAUniv Fed Sao Paulo, Escola Paulista Medicina, Dept Pharmacol, Sect Expt Endocrinol, Rua 03 maio 100,INFAR,Vila Clementino, BR-04044020 Sao Paulo, SP, BrazilCNPq: 401932/2013-3CNPq: 150066/2016-3CNPq: 101955/2015-4CNPq: 308349/2010-5FAPESP: 2010/52711-0FAPESP: 2009/14649-3National Institutes of Health Eunice Kennedy Shriver NICHD (NIH):R01-HD069654UK MRC: MR/N002970/1Web of Scienc