Ribeiro Camilla M, Ferreira Lucas G A, Thimoteo Daniel S, Smith Lee B, Hinton Barry T, Avellar Maria Christina W
Section of Experimental Endocrinology, Department of Pharmacology, Universidade Federal de São Paulo, Escola Paulista de Medicina, São Paulo, SP, Brazil.
MRC Centre for Reproductive Health, University of Edinburgh, The Queen's Medical Research Institute, Edinburgh, UK.
Mol Cell Endocrinol. 2017 Feb 15;442:142-152. doi: 10.1016/j.mce.2016.12.016. Epub 2016 Dec 15.
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.
沃尔夫管（WD）会经历由雄激素诱导的形态变化，形成附睾，附睾是精子成熟所必需的器官。雄激素在WD上皮中的作用涉及间充质来源的旁分泌因子，其作用机制仍知之甚少。在这里，我们研究了抗菌β-防御素SPAG11C作为导管形态发生中的一个新因子，其在产前定位于WD间充质中。使用了大鼠WD的器官型培养物和雄激素受体（AR）基因敲除小鼠（ARKO）的组织。我们的结果表明，雄激素/AR信号在发育中的WD中以不同方式调节SPAG11C在mRNA和蛋白质水平的表达。用重组人SPAG11C孵育的WD由于上皮细胞增殖减少而变短且卷曲程度降低，但细胞凋亡并未增加。我们的结果表明β-防御素SPAG11C是WD形态发生所需的雄激素靶点。这突出了β-防御素蛋白家族的多功能性及其对决定男性生殖成功的子宫内环境的潜在贡献。
