Oral exposure to low-dose bisphenol A induces hyperplasia of dorsolateral prostate and upregulates EGFR expression in adult Sprague-Dawley rats

Abstract

Prostate is sensitive to endocrine hormone level, and the synergetic effect of estrogen and androgen is critical in prostate growth. The change of signal pathways caused by the imbalance of estrogen and androgen might function in the occurrence of prostate diseases. As a well-known endocrine disruptor compound, bisphenol A (BPA) can disturb the normal function of endocrine hormone and affect prostate development. This study aims to investigate effects of BPA on the dorsolateral prostate (DLP) and the related gene expression of the tissue in adult Sprague- Dawley (SD) rats and to explore the mechanism for the effect of low-dose BPA on DLP hyperplasia. Three-month-old male SD rats were treated with BPA (10.0, 30.0, or 90.0 µg (kg.day)−1, gavage) or vehicle (gavage) for 4 weeks. BPA significantly increased the DLP weight, the DLP organ coefficient, and the prostate epithelium height ( p < 0.01) of rats dose-dependently. Microarray analysis and quantitative real-time polymerase chain reaction showed that BPA significantly upregulated the transcriptional levels of some genes, including pituitary tumor transforming gene 1, epidermal growth factor, Sh3kbp1, and Pcna. Furthermore, the expression of PCNA ( p < 0.01), androgen receptor ( p < 0.01), and EGF receptor (EGFR) ( p < 0.001) in DLP was increased significantly by BPA treatment, and the expression of estrogen receptor alpha was also upregulated. The findings evidenced that low-dose BPA could induce DLP hyperplasia in adult rats, and the upregulated EGF/EGFR pathway that was responsive to estrogen and androgen might play an essential role in the DLP hyperplasia induced by low-dose BPA.

Bisphenols Threaten Male Reproductive Health via Testicular Cells

“…As shown in previous studies, BPA contamination is related to development of prostate cancer and elevates centrosome amplification in vitro (78). In another study, BPA caused enlargement of prostate and increased EGFR mRNA level in mature Sprague-Dawley rats when administered orally (79). Another study demonstrated that BPA enhanced human prostate stem cell proliferation (80).…”

Breast and prostate glands affected by environmental substances (Review)

“…Similarly as in breast cancer, the influence of hormones should not be underestimated in PCa. It was observed that BPA alone was not enough to induce a prostate pathology, but it increased the prostate susceptibility to estrogen, thus contributing to carcinogenesis later in life; however, rats exposed to BPA in developmental phases with subsequent testosterone and estradiol treatment showed more relevant results (16), suggesting a possible synergy to induce prostate carcinogenesis (92).…”

“…Another study evaluated the effects of BPA on adult rats, despite the knowledge that aged rats were prone to develop prostate hyperplasia, and revealed an upregulation of ERα in adult rats (92). A molecular study observed that BPA treatment upregulated the pituitary tumor transforming gene 1, epidermal growth factor, Sh3kbp I and PCNA (92) involved in cell growth and proliferation.…”

Combined Effects of Different Endocrine-Disrupting Chemicals (EDCs) on Prostate Gland

“…Androgens physiologically control growth and functions of the prostate during, but it has been shown that they can also be involved in carcinogenesis [ 81 ]. The interaction among androgens and AR promotes prostate cell proliferation by activating AR-responsive genes and pathways in androgen-dependent adult prostate growth [ 82 , 83 ]. For this reason, AR has a major drug target in BPH [ 83 , 84 ] and PC [ 81 , 85 ].…”

“…The interaction among androgens and AR promotes prostate cell proliferation by activating AR-responsive genes and pathways in androgen-dependent adult prostate growth [ 82 , 83 ]. For this reason, AR has a major drug target in BPH [ 83 , 84 ] and PC [ 81 , 85 ]. Moreover, it has been demonstrated that estrogens play an important role in male sex hormone secretion as well as in the growth, differentiation, and homeostasis of both normal and cancer prostate cells [ 81 , 86 , 87 ].…”