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Bacterial Lipopolysaccharide-Induced Inflammation Compromises Testicular Function at Multiple Levels in Vivo¹

Institute of Reproduction and Development, Monash University, Monash Medical Center, Clayton, Victoria 3168, Australia

Address all correspondence and requests for reprints to: Dr. M. P. Hedger, Institute of Reproduction and Development Monash University, Monash Medical Center, Clayton, Victoria 3168, Australia. E-mail: mark.hedger{at}med.monash.edu.au

While it is well known that serious illness and inflammation reduce male fertility, the mechanisms involved are poorly understood. In adult male rats, a single injection of lipopolysaccharide at doses that induced either mild or severe inflammation, caused a biphasic decline in Leydig cell testosterone production and gonadotropin responsiveness. In the high dose group only, serum LH levels also were reduced; however, intratesticular testosterone concentrations remained at a level adequate to support qualitatively normal spermatogenesis in both treatment groups. Testicular interstitial fluid formation also declined in a dose-dependent fashion after lipopolysaccharide treatment. In the high dose group only, these hormonal and vascular changes were accompanied by an increase in endothelial permeability, microhemorrhage, and inflammatory cells in the testis, followed by vacuolization of round spermatid nuclei, disruption of Sertoli-germ cell contacts at stages I–IV of the cycle of the seminiferous epithelium, and subsequently apoptosis of spermatocytes at stages II–V. These data indicate that mild inflammation causes local inhibition of Leydig cell function with relatively little spermatogenic damage. The pathological changes in spermatogenic function during severe inflammation are most likely due to direct effects of inflammatory mediators on the seminiferous epithelium or testicular vasculature, rather than inhibition of the brain-pituitary-Leydig cell axis.

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