Are expression and localization of tight and adherens junction proteins in testes of adult boar affected by foetal and neonatal exposure to flutamide?

作者：Hejmej A^*; Kopera I; Kotula Balak M; Lydka M; Lenartowicz M; Bilinska B

来源：International Journal of Andrology, 2012, 35(3): 340-352.

DOI：10.1111/j.1365-2605.2011.01206.x

• blood-testis barrier
• boar
• flutamide
• N-cadherin
• occludin
• testis
• ZO-1
• ss-catenin

Several recent studies have indicated that androgen disruption induced by the administration of anti-androgen flutamide during critical developmental stages results in various reproductive abnormalities, mainly in rodents. However, scarce data are available regarding the alterations caused by this toxicant on cellcell adhesion molecules. Of note, there is no report on the expression and regulation of tight and adherens junction proteins in the boar. Therefore, the purpose of this study was to analyse whether foetal and neonatal exposure to flutamide affects the expression and distribution of ZO-1, occludin, beta-catenin, and N-cadherin in testes of adult pigs. Moreover, to evaluate whether androgen signal was altered in the boar, testicular levels of testosterone and oestradiol and the expression of androgen receptor were examined. Flutamide (50 mg/kg bw) was injected into pregnant gilts during gestational days 2028 and 8088 (GD20, GD80), and into male piglets on postnatal days 210 (PD2). In the testes of all flutamide-exposed boars, expressions of ZO-1, N-cadherin and beta-catenin were significantly decreased at mRNA and protein level, whereas expression of occludin was unchanged when compared with the controls. In addition, in severely damaged seminiferous tubules of PD2 pigs, mislocalization of ZO-1, N-cadherin and beta-catenin was observed. Changes in junction protein expressions were accompanied by disturbed intratesticular androgenoestrogen balance, although androgen receptor expression was not altered. Taken together, these results demonstrate that blockade of androgen action by flutamide during both gestational and neonatal periods affects the expression of ZO-1, N-cadherin and beta-catenin in adult pig testes. Of concern, neonatal window seems to be most critical for the organization of BTB and consequently for normal spermatogenesis in the boar. It is likely that altered expression of junction proteins is related to insufficient testosterone production and/or excessive oestradiol synthesis, which may result from impaired Leydig cell function.

• 出版日期2012-6