Effects of Wnt/β-catenin signaling on bisphenol A exposure in male mouse reproductive cells

Abstract

Bisphenol A (BPA) is a chemical used in numerous consumer products that is able to interfere with the mammalian endocrine system. The aim of the present study was to investigate the effects of BPA on male mouse reproductive cells following prenatal to postnatal exposure. In addition, the influence of BPA was detected on the expression levels of β‑catenin and dickkopf WNT signaling pathway inhibitor 1 (DKK‑1) during the differentiation of spermatogenic cells in the mouse testes. β‑catenin and DKK‑1 are two important proteins of the Wnt/β‑catenin signaling pathway. On gestational day 1, pregnant ICR mice were randomly divided into four groups: A dimethyl sulfoxide group, and three groups treated with various concentrations of BPA (0.5, 10, and 50 µg/kg). BPA was administered from gestational day 1 to weaning on postnatal day (PND) 42. The number of murine pups and the male:female ratio was recorded for each group. On PND 42, the male pups were sacrificed and their wet weights and testicular coefficients were measured. Immunohistochemical and western blot analyses were used to detect the protein expression of β‑catenin and DKK‑1 in the testicular tissue samples of the six‑week‑old male mice. The results indicated that the number of murine pups, as well as the testicular viscera coefficient of the male mice, significantly decreased in the BPA‑treated groups, as compared with the control group (P<0.05, P<0.01); however, no significant difference was observed in the male/female ratio in the BPA‑treated groups, as compared with the control group (P>0.05). The results from the immunohistochemical and western blot analyses indicated that the protein expression of β‑catenin and DKK‑1 were significantly increased in the BPA‑treated groups, as compared with the control group, and the distribution of spermospore and Leydig cells also increased in the testes. These results suggest that high expression levels of β‑catenin and DKK‑1 may participate in BPA‑induced pathogenesis in male mouse reproductive cells.

Bisphenol A impaired cell adhesion by altering the expression of adhesion and cytoskeleton proteins on human podocytes

“…Herein our results clearly indicated that BPA significantly increased the protein expression of tenascin-C as well as β-catenin. An interaction between β-catenin and tenascin-C 66,67 is known to occur and may also trigger podocytopathy as described in other cell types 68,69 .…”

Bisphenol A and di(2-ethylhexyl) phthalate exert divergent effects on apoptosis and the Wnt/β-catenin pathway in zebrafish embryos: A possible mechanism of endocrine disrupting chemical action

“…Defects and mutations in the Wnt/β-catenin signaling pathway are usually related to human birth defects, cancer and other diseases (Logan and Nusse, 2004). Although endocrine disrupting chemical exposure during the early stages of fetal development has been linked to developmental delays and childhood cancers, to date only a few studies have reported their effects on the Wnt/β-catenin signaling pathway (Fang et al, 2015).…”

Wnt pathway: A mechanism worth considering in endocrine disrupting chemical action

“…Aberrant β-catenin expression is a key marker of Wnt-signaling activation and has been reported in male mouse reproductive cells by Fang et al (2015). In that study Fang et al (2015) evaluated the toxicological effects of prenatal to postnatal BPA exposure on the reproductive system of Institute of Cancer Research (ICR) male murine pups by evaluating the association between Wnt signaling and testis development. The expressions of β-catenin and DKK-1 were determined by immunohistochemical and western blot methods in the testicular tissues of the 6-week-old male mice.…”

“…Increased β-catenin levels in this study indicate the inhibitory effect of BPA on β-catenin degradation (Kong and Zhang, 2009; Ye et al, 2011). On the other hand, the association of Wnt/β-catenin signaling pathway and BPA-induced inhibition of male mouse reproductive cell growth and development remains to be further elucidated (Fang et al, 2015).…”