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

- SPAG11C immunoreactivity is exclusively found in the Wolffian duct mesenchyme.
- Androgen receptor signaling regulates SPAG11C expression in developing Wolffian duct.
- Recombinant hSPAG11C protein affects Wolffian duct morphogenesis ex vivo.
- The hSPAG11C mechanism relies on regulation of ductal epithelial cell proliferation.
- The β-defensin SPAG11C is suggested as a new player in 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 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.