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(Reference retrieved automatically from Web of Science through information on FAPESP grant and its corresponding number as mentioned in the publication by the authors.)

pididymal embryonic development harbors TLR4/NFKB signaling pathway as a morphogenetic playe

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Ferreira, Lucas G. A. [1] ; Nishino, Fernanda A. [1] ; Fernandes, Samuel G. [1] ; Ribeiro, Camilla M. [1, 2] ; Hinton, Barry T. [3] ; Avellar, Maria Christina W. [1]
Total Authors: 6
[1] Univ Fed Sao Paulo, Dept Pharmacol, Escola Paulista Med, BR-04044020 Sao Paulo, SP - Brazil
[2] Ctr Univ Planalto Araxa UNIARAXA, BR-38180084 Araxa, MG - Brazil
[3] Univ Virginia Hlth Syst, Dept Cell Biol, Charlottesville, VA 22903 - USA
Total Affiliations: 3
Document type: Journal article
Web of Science Citations: 0

The Wolffian duct (WD) is an embryonic tissue that undergoes androgen-induced morphological changes to become the epididymis. Toll-like receptor 4 (TLR4)- and nuclear factor kB (NFKB)-induced effectors are expressed in the adult epididymis and represent important players in epididymal innate immune responses. TLR4/NFKB signaling pathway is evolutionarily conserved and plays a critical morphogenetic role in several species; however, its function during WD morphogenesis is unknown. We hypothesized that TLR4/NFKB pathway plays a role during WD development. Here we examined TLR4 expression and regulation of TLR4-target genes during rat WD morphogenesis between embryonic days (e) 17.5-20.5. The functionality of TLR4/NFKB signaling was examined using WD organotypic cultures treated with lipopolysaccharide (LPS) from E. coli (TLR4 agonist) and PDTC (NFKB inhibitor). TLR4 was detected at mRNA level in e17.5 (uncoiled duct) and e20.5 (coiled duct) WDs, and spatio-temporal changes in TLR4 immunoreactivity were observed between these two time points. Expression level analysis of a subset of TLR4-regulated genes showed that TLR4/NFKB pathway was activated after exposure of cultured WD to LPS (4 h), an event that was abrogated by PDTC. Long-term exposure of cultured WDs to LPS (96 h) resulted in dysregulations of morphogenetic events and LAMA1 immunodistribution changes, suggesting the extracellular matrix at the intersection between WD morphogenesis and balance of innate immune components. Our results unveil the epididymal morphogenesis as an event equipped with TLR4/NFKB signaling components that may serve developmental functions, and eventually transition to host defense function when the fetus is exposed to an infectious or noninfectious threat. (AU)

FAPESP's process: 16/22118-1 - Androgen regulation, biological activity and cell signaling of beta-defensins in the epididymis morphogenesis
Grantee:Lucas Garcia Alves Ferreira
Support Opportunities: Scholarships in Brazil - Master
FAPESP's process: 19/02633-7 - Investigating the mechanism of action and function of innate immunity components in the morphogenesis of the epididymis
Grantee:Fernanda Akane Nishino
Support Opportunities: Scholarships in Brazil - Scientific Initiation