In utero exposure to tributyltin alters the expression of e‐cadherin and localization of claudin‐1 in intercellular junctions of the rat ventral prostate

Abstract

Tributyltin (TBT) is an environmental contaminant, exhibiting well-established toxicity to reproductive systems in aquatic organisms. Little information exists regarding the effects of TBT on mammalian reproduction. Cellular junctions are crucial for sperm development and maturation. Intercellular tight junctions are formed by transmembrane proteins such as claudins (Cldns), while the formation of tight junctions involves signaling components of adhering junctions, comprised of cadherins. The objectives of this study were to determine the effects of in utero exposure to TBT on the rat ventral prostate. Pregnant Sprague-Dawley rats were given doses of TBT (2.5, 10, or 20 mg/kg) throughout gestation and sacrificed at Day 91. Ventral prostate weights of TBT-treated rats were decreased in all treatment groups. Results of gene expression macro-array analysis indicated that numerous genes related to cellular adhesion and cell polarity were affected. Cldn-1 mRNA levels decreased after exposure to TBT. Cldn-1 was immunolocalized to the apical lateral margins of adjacent prostatic epithelial cells in controls, but was increasingly dispersed along the lateral plasma membrane with increasing TBT dose, suggesting that the targeting of Cldn-1 or its localization to tight junctions was altered as a result of fetal TBT exposure. E-cadherin mRNA levels and immunolocalization were decreased in a dose-dependent manner. These data indicate that in utero TBT exposure results in permanent alterations in ventral prostate and that these are associated with alterations in the expression and distribution of cell adhesion and tight junctional proteins.

Alterations in male rats following in utero exposure to betamethasone suggests changes in reproductive programming

“…This is reflected by the significantly higher ventral prostate weight observed in treated adults when androgen levels are similar to those in control rats. While androgens regulate prostate weights, toxicants such as tributyltin have been reported to alter prostate weights independent of circulating androgens [40]. Indeed, Zhao et al [41] demonstrated androgen-independent growth of prostate cells mediated by glucocorticoids.…”

Cell junctions in the prostate: an overview about the effects of Endocrine Disrupting Chemicals (EDCS) in different experimental models

“…In this study, E-cadherin and claudin-1 expression levels decreased in a dosedependent response, while claudin-3 and -8 increased in high-dose treatments, suggesting that some compensatory effect among the various claudins present in the ventral prostate. In addition, claudin-1 immunolocalization was shown to be spread throughout the plasma membrane in animals exposed to TBT, rather than restricted to the apical margin of adjacent epithelial cells, as in the control group, suggesting possible changes in the tight junctions function [23].…”

“…In a study with pregnant rats, Barthelemy et al [23] observed a significant dose-dependent decrease in E-cadherin mRNA levels in the ventral prostate of adult rats exposed in utero to increasing doses of TBT (2.5, 10, and 20 mg/kg). G-proteins play an essential role in the signaling process, implicating cell adhesion molecules such as cadherins [23]. Microarray analyses indicated that four Gproteins, Rab16, Rab 14, RaI A and GNAI2, significantly decreased in the TBT-treated rats, indicating a possible imbalance in the process related to establishment and/or maintenance of cell polarity.…”

“…Tight junctions are junctional complexes formed by integrated transmembrane proteins such as occludins and claudins that create a continuous intercellular barrier between epithelial cells, maintaining cellular polarity and controlling the passage of molecules through the epithelium [7,23]. Some claudins (claudin-3, -4, -5, -8 -10) are located between the prostate luminal epithelial cells while others (claudin-1 and -7) confer cellular adhesion and signaling to the extracellular matrix [7,24].…”

“…Tributyltin (TBT) is an organotin used as an antifouling agent in paint for boats, in wood preservatives and as a disinfectant in water cooling systems [38]. In a study with pregnant rats, Barthelemy et al [23] observed a significant dose-dependent decrease in E-cadherin mRNA levels in the ventral prostate of adult rats exposed in utero to increasing doses of TBT (2.5, 10, and 20 mg/kg). G-proteins play an essential role in the signaling process, implicating cell adhesion molecules such as cadherins [23].…”