Ultrastructural alterations of the prostate after bacterial infection under different hormonal status.

QUINTAR A; LEIMGRUBER C.; MALDONADO C.A.

Rosario, Argentina

Congreso; 10th Inter-American Congress of Electron Microscopy 2009 (CIASEM) 1st Congress of the Argentine Society of Microscopy SAMIC 2009.; 2009

Interamerican Committee of Societies for Electron Microscopy

ULTRASTRUCTURAL ALTERATIONS OF THE PROSTATE AFTER BACTERIAL INFECTION UNDER DIFFERENT HORMONAL STATUS Quintar AA, Leimgruber C & Maldonado CA Centro de Microscopía Electrónica. Universidad Nacional de Córdoba. Argentina. cmaldon@cmefcm.uncor.edu The prostate gland consists of a secretory epithelium and a stroma formed by periacinar smooth muscle cells and scarce fibroblasts. The organization and functional status of both compartments are under androgen control mediated by epithelial-stromal interactions, being both highly sensitive to changes in the hormonal levels (Cunha et al, 2004). In addition, we previously demonstrated that prostate epithelial and stromal compartments respond to an inflammatory microenvironment induced by E. coli, determining a characteristic morphologic reaction (Quintar et al, 2006). The main goal of the present study was to evidence if androgen levels could modulate the morphological response of the prostate gland to infection with E. coli. For this purpose, we performed a prostatitis model in Wistar rats by inoculating intraprostatically 108 CFU/ml of E. coli under three different hormonal status: (i) the INF group, infected rats with normal androgen level; (ii) CAST+INF, which were castrated on the day before bacterial inoculation, and (iii) TEST+INF, which were also castrated and infected, but daily treated with 2,5mg/rat/d of testosterone propionate for 5 days. Control groups were comprised of animals injected with the respective vehicle. The morphology of the ventral prostate was analyzed on the fifth day after bacterial infection by both light and electron microscopy. At the same time, we evaluated by inmunoelectronmicrocopy the immunomodulatory and antiinflammatory protein Prostatein (PBP) in the epithelium and -smooth muscle actin (ACTA2) in the prostatic stroma. The INF group showed an atrophied epithelium with decreased expression of PBP. Neutrophils filled the acinar lumen exhibiting active phagocytosis of bacteria, being apoptotic a few of them (Fig. 1). Surprisingly, prostatic reaction to infection was not restricted to the epithelial compartment but the periacinar smooth muscle cells also exhibited cellular hypertrophy, presence of organelles for protein synthesis around the nuclei, and loss of contractile phenotype (Fig. 4). Immunostaining for ACTA2 showed no reactivity in the perinuclear area, being confined to peripheral regions of the smooth muscle. In TEST+INF group, the high levels of testosterone intensified the acquisition of a secretory phenotype by smooth muscle cells after bacterial infection and the consequent loss of contractile features as well as the disruption of the periacinar layer (Fig. 5). As could be expected, testosterone stimulated epithelial cells, which exhibited a well developed Golgi complex (Fig. 2), and prevented the atrophy observed in INF. However, there was a large number of neutrophils accumulated in the acinar lumen containing several fragments of bacteria (Fig. 7), as in the INF group. The combination of castration and infection (CAST+INF) resulted in a better preservation of tissue architecture comparing to infection and castration alone. Infection inhibited atrophy triggered by androgen deprivation, showing a well preserved epithelium with prominent Golgi complex and secretory vesicles (Fig. 3). Few neutrophils were seen in the lumen and most of them were apoptotic (Fig. 8). In the stroma, smooth muscle cells conserved the contractile phenotype (Fig. 6), which collaborated to maintain the integrity of the periacinar layer. Castration performed simultaneously with infection resulted in a more effective elimination of bacteria as was determined by electron microscopy and inmunocytochemistry for E. coli. CONCLUSION: These results suggest that testosterone promote an enhancement in stromal and epithelial reaction to bacterial infection contributing to amplify the prostatic inflammation. Meanwhile, castration could better preserve prostate specific activities and cell phenotypes, which collaborated for a more accurate control of infection and inflammation.