Androgen regulation, biological activity and cell signaling of beta-defensins in the epididymis morphogenesis

• Grant number: 16/22118-1
• Support Opportunities: Scholarships in Brazil - Master
• Start date: March 01, 2017
• End date: March 02, 2019
• Field of knowledge: Biological Sciences - Pharmacology - Biochemical and Molecular Pharmacology
• Agreement: Coordination of Improvement of Higher Education Personnel (CAPES)
• Principal Investigator: Maria Christina Werneck de Avellar
• Grantee: Lucas Garcia Alves Ferreira
• Host Institution: Escola Paulista de Medicina (EPM). Universidade Federal de São Paulo (UNIFESP). Campus São Paulo. São Paulo , SP, Brazil
• Associated scholarship(s): 18/13816-2 - Intra- and extracellular fates of the beta-defensin SPAG11C transiently expressed in cultured cells and the influence of a potential protein partner, BE.EP.MS

Abstract

Reproductive disorders related to male reproductive tract are of public health interest. Many reproductive problems in adult men have unknown etiology and part of them is due to the influence of environmental factors affecting the morphogenesis and the masculinization of the male reproductive tract. In adults, the epididymis is an essential organ for sperm maturation and production of viable spermatozoa, which are required for fertilization. The mesonephric duct (also known as Wolffian duct), the anlagen of the epididymis, goes through a process of tubuloepithelial morphogenesis induced by androgens that originates the epididymis. Disruption of the morphological differentiation of this structure may result in infertility at adulthood. Therefore, there is a need for a better understanding of the mechanisms and mediators of the androgen action that govern epididymis development. In the last years our research group has identified the beta-defensin SPAG11C (sperm associated antigen 11 C) as an androgen-dependent mesenchymal factor that has a role in modulating the mesonephric duct morphogenesis in rats. Here we present the basis of this discovery and the experimental data that expanded our view of beta-defensins in this embryonic tissue and gave support to our aim to investigate the androgen regulation and the functional aspects of beta-defensins during the rat epididymis morphogenesis, focusing on beta-defensins DEFB1 (defensin beta 1) and DEFB2. For this purpose, we will evaluate: a) the androgenic modulation of beta-defensins DEFB1 and DEFB2 in ex vivo cultured mesonephric duct; b) the androgenic modulation of these two beta-defensins in mesonephric duct from androgen receptor knockout mice (ARKO); c) the effects of beta-defensins DEFB1 and DEFB2 (recombinant proteins) on the morphogenesis of the ex vivo cultured mesonephric duct and d) the cellular and molecular basis of the effects of beta-defensins in ex vivo cultured mesonephric duct. (AU)

Scientific publications

(References retrieved automatically from Web of Science and SciELO through information on FAPESP grants and their corresponding numbers as mentioned in the publications by the authors)

FERREIRA, LUCAS G. A.; NISHINO, FERNANDA A.; FERNANDES, SAMUEL G.; RIBEIRO, CAMILLA M.; HINTON, BARRY T.; AVELLAR, MARIA CHRISTINA W.. pididymal embryonic development harbors TLR4/NFKB signaling pathway as a morphogenetic playe. JOURNAL OF REPRODUCTIVE IMMUNOLOGY, v. 149, FEB 2022. (16/22118-1, 19/02633-7)