Transforming Growth Factor Beta 1 Induces Tight Junction Disruptions and Loss of Transepithelial Resistance Across Porcine Vas Deferens Epithelial Cells

• Published in: Biology of reproduction Vol. 86; no. 2; p. 36
• Main Authors: PIERUCCI-ALVES, Fernando, YI, Sheng, SCHULTZ, Bruce D
• Format: Journal Article
• Language: English
• Published: Madison, WI Society for the Study of Reproduction 01.02.2012; Society for the Study of Reproduction, Inc
• Subjects: Animals; Anions; Biological and medical sciences; Cell culture; Cell Membrane Permeability - drug effects; Cell Membrane Permeability - physiology; Cells, Cultured; Claudins - metabolism; Cytokines; Data processing; Diffusion; Electrophysiological Phenomena; Epithelial cells; Epithelial Cells - drug effects; Epithelial Cells - physiology; Epithelium; Fertility; Forskolin; Fundamental and applied biological sciences. Psychology; Male; MAP kinase; Membrane Proteins - metabolism; Microenvironments; Mitogen-Activated Protein Kinase 11 - antagonists & inhibitors; Models, Animal; Occludin; Patch-Clamp Techniques; Receptor mechanisms; Semen; Solutes; Sperm; Swine; Tight junctions; Tight Junctions - drug effects; Tight Junctions - metabolism; Transforming Growth Factor beta1 - pharmacology; Transforming growth factor- beta; Transforming growth factor- beta 1; Vas deferens; Vas Deferens - cytology; Vertebrates: reproduction; Semen pathway; growth factors; Transforming growth factor; Cytokine; Cell junction; Male; Male genital duct; Male genital system; Vas deferens; Pig; Vertebrata; Reproduction; Mammalia; Animal; Epithelial cell; Tight junction; cytokines; Artiodactyla; male epithelial barrier; male reproductive tract; Ungulata; Growth factor
• ISSN: 0006-3363; 1529-7268; 1529-7268
• DOI: 10.1095/biolreprod.111.092262

Epithelial cells lining the male excurrent duct contribute to male fertility by employing a number of physiological mechanisms that generate a luminal microenvironment conducive to spermatozoa maturation and storage. Among these mechanisms, male duct epithelia establish intercellular tight junctions that constitute a barrier to paracellular diffusion of water, solutes, large molecules, and cells. Mechanisms regulating the male duct epithelial barrier remain unidentified. Transforming growth factor beta (TGFB) is a regulatory cytokine present in high concentrations in human semen. This study examined whether TGFB has any effects on epithelial function exhibited by primary cultures of porcine vas deferens epithelia. TGFB1 exposure caused a 70%-99% decrease in basal transepithelial electrical resistance (R(TE), a sensitive indicator of barrier integrity), while a significant decrease in anion secretory response to forskolin was detected at the highest levels of TGFB1 exposure employed. SB431542, a selective TGFB receptor I (TGFBR1) inhibitor, prevented decreases in barrier function. Results also demonstrated that TGFB1 exposure modifies the distribution pattern of tight junction proteins occludin and claudin 7. TGFBR1 is localized at the apical border of the native porcine vas deferens epithelium. Pharmacological inhibition of mitogen-activated protein kinase (MAPK) 11 (also known as p38-MAPK) did not alter the effect of TGFB1 on R(TE) significantly. These data suggest that epithelia lining the vas deferens are subject to disruptions in the physical barrier if active TGFB becomes bioavailable in the luminal fluid, which might be expected to compromise fertility.