Abstract P146: Testicular Inflammation Is Associated With Immune Cell Infiltration And Lymphangiogenesis In L-NAME-induced Hypertension
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Hypertension (HTN) is associated with reduced fertility in men. Although numerous studies report that HTN disrupts hormonal balance in men, less is known about the direct effect of HTN on testes and how HTN influences testicular inflammation and lymphatics. We hypothesized that HTN increases testicular lymphatic vessel density and this is associated with immune cell infiltration and inflammation. Male mice (8 weeks old) were made hypertensive by providing them with L-arginine methyl ester hydrochloride (L-NAME) (0.5 mg/mL) in the drinking water for 3 weeks and control mice received tap water. Testes of hypertensive mice had a significant increase in gene expression of the lymphatic vessel markers Lyve-1 (17.7 2.1 fold; p<0.05), Podoplanin (6.7 1.2 fold; p<0.05), and Prox-1 (68.1 10.6 fold; p<0.05), the lymphangiogenic growth factors VEGF-C (5.7 1.1 fold; p<0.05), VEGF-D (2.2 0.7 fold; p<0.05), and VEGF-A (5.8 1.1 fold; p<0.05) and their receptors VEGFR-2 (8.0 2.0 fold; p<0.05) and VEGFR-3 (25.4 3.5 fold; p<0.05). There was also a significant increase in the expression of the pro-inflammatory cytokines TNF-a (24.0 6.8 fold; p<0.05), IFN-g (17.5 3.0 fold; p<0.05), IL-1b (4.2 1.2 fold; p<0.05), IL-6 (24.8 13.0 fold; p<0.05), and IL-17 (4.4 0.4 fold; p<0.05). There were also increases in the lymphatic endothelial cell-derived immune cell trafficking chemokines CCL21 (7.8 1.7 fold; p<0.05) and CCL19 (9.0 4.1 fold; p<0.05) and their receptor CCR7 (9.6 3.2 fold; p<0.05), as well as the cell adhesion molecule ICAM (6.2 1.0 fold; p<0.05) in testes of hypertensive mice. Flow cytometry analysis revealed an increased accumulation of F4/80+ macrophages in the testes from hypertensive mice. Together, these data demonstrate that HTN induces inflammation-associated lymphangiogenesis in testes, in association with immune cell infiltration. It is possible that increasing testicular lymphatics may reduce inflammation and improve reproductive function in hypertensive men.
