Effect of di-(2-ethylhexyl)phtalate (DEHP) on N-cadherin and catenin expression in rat testis.

SOBARZO C.; LUSTIG L.; DENDUCHIS B.

Seul, Corea

Congreso; 8th International Congress of Andrology; 2005

International Society of Andrology

EFFECT OF DI-(2-ETYLHEXYL) PHTHALATE (DEHP) ON N-CADHERIN AND  CATENIN PROTEIN EXPRESSION IN RAT TESTIS Cristian Sobarzo1,2, Livia Lustig1 and Berta Denduchis1* 1Centro de Investigaciones en Reproducción, Facultad de Medicina Universidad de Buenos Aires, Buenos Aires, Argentina. 2Facultad de Ciencias, Universidad Católica de Temuco, Chile.     Objectives: The aim of this work was to study the effect of DEHP, a specific Sertoli cell toxicant, on the testicular expression of the classic N-cadherin and  a, b and pp120 catenin proteins, in rats. Methods: DEHP was administered by gavage to male Sprague-Dawley rats (25-day old) in a dose of 2 g DEHP/5 ml corn-oil/kg body weight during 2 days (experimental rats, E) or with vehicle corn oil in the same conditions ( control rats, C). Animals were sacrificed 24 h (E1 and C1 groups) or 30 days after treatment (recovery groups E2 or C2).  Testes were removed for histopathology, apoptosis and immunofluorescence (IF) techniques and Western blot (Wb) analyses. Results:  Various degrees of damage and cell sloughing of the germinal epithelium and seminiferous tubule atrophy were observed in testes of E1 rats. Testes of recovery rats shows an incomplete germ cell repopulation compare to C2. No lesions were detected in C groups. A significant increase of the apoptotic index by TUNEL in the testis of E1 rats (15%) compared to C1 rats (4%). Apoptosis was mainly localized in spermatocytes and few spermatogonia.  In E and C rats, N-cadherin was localized at the basal compartment of the seminiferous tubules, with a linear IF pattern. However, a higher intensity of IF was observed in the testis of E1 compared to C1 rats. A similar immunolocalization was detected for a, b and pp120 catenins but with a milder IF. No difference in the expression of these molecules was observed among E and C rats. By Wb analysis a significant increase in N-cadherin and  a, b and pp120 catenin proteins  expression was observed in the testis of E1 compared to C1 rats. Testes of E2 rats showed the same N-cadherin and catenin protein expression as C2 rats. Conclusions: we demonstrated  that DEHP induces in rat testis a germ cells damage with increase of germ cell apoptosis and an up-regulation of N-cadherin and  a,  b and pp120 catenin expression. Data suggest that DEHP induces a deregulation of molecules involved in cell adherens junctions. That might affect Sertoli cell function and, consequently, the germinal epithelium.   *e-mail: ciruba@fmed.uba.ar