title: Novel androgen-induced activity of an antimicrobial β-defensin: Regulation of Wolffian duct morphogenesis.
abstract: 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 β-defensin SPAG11C 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 SPAG11C expression at mRNA and protein levels in the developing WD. WDs incubated with recombinant human SPAG11C were shorter and less coiled as a result of reduced epithelial cell proliferation, but not increased apoptosis. Our results suggested β-defensin SPAG11C as an androgen-target required for WD morphogenesis. This highlights the multifunctional repertoire of the β-defensin protein family and their potential contribution to the in utero environment that determines male reproductive success.
authors.affiliation: Section of Experimental Endocrinology, Department of Pharmacology, Universidade Federal de São Paulo, Escola Paulista de Medicina, São Paulo, SP, Brazil.
authors.forename: Camilla M
authors.initials: CM
authors.lastname: Ribeiro
authors.affiliation: Section of Experimental Endocrinology, Department of Pharmacology, Universidade Federal de São Paulo, Escola Paulista de Medicina, São Paulo, SP, Brazil.
authors.forename: Lucas G A
authors.initials: LG
authors.lastname: Ferreira
authors.affiliation: Section of Experimental Endocrinology, Department of Pharmacology, Universidade Federal de São Paulo, Escola Paulista de Medicina, São Paulo, SP, Brazil.
authors.forename: Daniel S
authors.initials: DS
authors.lastname: Thimoteo
authors.affiliation: MRC Centre for Reproductive Health, University of Edinburgh, The Queen's Medical Research Institute, Edinburgh, UK.
authors.forename: Lee B
authors.initials: LB
authors.lastname: Smith
authors.affiliation: Department of Cell Biology, University of Virginia, School of Medicine, Charlottesville, VA, USA.
authors.forename: Barry T
authors.initials: BT
authors.lastname: Hinton
authors.affiliation: Section of Experimental Endocrinology, Department of Pharmacology, Universidade Federal de São Paulo, Escola Paulista de Medicina, São Paulo, SP, Brazil. Electronic address: avellar@unifesp.br.
authors.forename: Maria Christina W
authors.initials: MC
authors.lastname: Avellar
mesh_terms: D000728:Androgens / Q000494:pharmacology*; D000818:Animals; D000890:Anti-Infective Agents / Q000494:pharmacology*; D000954:Antigens, Surface / Q000378:metabolism; D017209:Apoptosis / Q000187:drug effects; D049109:Cell Proliferation / Q000187:drug effects; D004822:Epididymis / Q000187:drug effects / Q000378:metabolism; D004848:Epithelium / Q000187:drug effects / Q000378:metabolism; D005260:Female; D018507:Gene Expression Regulation, Developmental / Q000187:drug effects; D006801:Humans; D008297:Male; D051379:Mice; D018345:Mice, Knockout; D009024:Morphogenesis / Q000187:drug effects*; D038081:Organogenesis / Q000187:drug effects; D051381:Rats; D017208:Rats, Wistar; D011944:Receptors, Androgen / Q000378:metabolism; D014928:Wolffian Ducts / Q000187:drug effects* / Q000378:metabolism; D023083:beta-Defensins / Q000494:pharmacology*
chemical_list: D000728:Androgens; D000890:Anti-Infective Agents; D000954:Antigens, Surface; D011944:Receptors, Androgen; D023083:beta-Defensins
keywords: Androgen; Epididymis; Innate immunity; Male infertility; Wolffian duct; β-defensin