Exposure to bisphenol A (BPA) in Wistar rats reduces sperm quality with disruption of ERK signal pathway

Abstract

Bisphenol A (BPA) is an estrogenic environmental toxin widely used in the production of plastics and ubiquitous human exposure to this chemical has been proposed to be a potential risk to human health. Exposure to BPA can negatively impact sperm quality. However, the mechanism remains largely unknown. The objectives of this study were to assess the role of BPA on sperm quality and explore the possible mechanisms. The Wistar male rats (aged 28 days) were administered BPA by oral gavage for 28 days at dose of 50, 100 and 200 mg/kg/day; meanwhile, the negative control with corn oil (0 mg/kg/day BPA) and positive control with E2 at the dose of 100 μg/kg/day. The sperm density, sperm activity and sperm survival rate were analyzed byCASA system, and the sperm abnormality rate was analyzed by improved Papanicolaou stained. The protein expression levels of Src/p-Src, ERK1/2, p-ERK1/2 and CREB/p-CREB were detected by Western bolt. The results showed that the body weight gain, testes weight, testis coefficient, sperm density, sperm activity, sperm survival rate and protein expression levels of p-ERK1, p-ERK2 and p-CREB decreased, but the sperm abnormality rate increased with increasing BPA concentrations. There were positive correlations between sperm density, sperm activity and sperm survival rate with protein expression levels of p-ERK1, p-ERK2 and p-CREB, and negative correlations between sperm abnormality rate with the protein expression levels of p-ERK1, p-ERK2 and p-CREB. Results from the structural equation model demonstrated that BPA retained a significant negative effect to p-ERK, whereas p-ERK retained a significant positive effect to sperm quality and acted as the mediate variable. This study provides a novel insight regarding the potential role of p-ERK1 and p-ERK2 protein kinase on reproductive toxicity of BPA. The adverse effects of BPA on adult male sperm quality may be through the induction of the disruption of ERK signal pathway. However, additional research is needed to confirm our findings and to further test the suggested potential mechanisms.

Bisphenol A induced oxidative stress and apoptosis in mice testes: Modulation by selenium

“…Thus, its continuous exposure and its ubiquitous presence in the environment have raised public health concerns (Bergman, Heindel, Jobling, Kidd, & Zoeller, ). Population‐based (Meeker et al., (); Li et al., () and animal‐based studies have reported male reproductive abnormalities resulting from BPA exposure such as state of hypogonadotropic hypogonadism (Wisniewski et al., (), adverse effects on morphology, growth and sexual development (Lam et al., ) and also endocrine and reproductive dysfunctioning (Milla, Depiereux, & Kestemont, ).…”

Bisphenol A Affects on the Functional Properties and Proteome of Testicular Germ Cells and Spermatogonial Stem Cells in vitro Culture Model

“…As an EDC, BPA has the potential to work as a weak estrogen receptor α/β (ERα/β) agonist 18 and to alter hormonal signal through binding to ERs on male germ cells. So, BPA related devastating effects such as low spermatozoa count 19 , sperm protein alteration 20 , toxicity development in spermatozoa via DNA damage 21 , DNA methylation 22 and oxidative stress 23 have been studied well. Moreover, studies like BPA induced disruption in meiotic progression during spermatogenesis 24 and reduction in chromosome crossover 25 have also been reported.…”

Anticancer properties of green‐synthesised zinc oxide nanoparticles using Hyssopus officinalis extract on prostate carcinoma cells and its effects on testicular damage and spermatogenesis in Balb/C mice

“…Different functional and morphological disorders have been reported on the testicular tissue following the in vivo exposure to nanoparticles (Asare et al, ; Komatsu et al, ). Inducing the oxidative stress by generating the reactive oxygen species (ROS) and free radicals (Zhang et al, ), suppression of spermatogenesis (Wisniewski et al, ) and alteration of testicular enzyme activity and hormones are the prevalent effects of nanoparticles on testis (Li et al, ). The histopathological investigation showed that administration of ZnO‐NPs affects the spermatids and spermatocyte quality as well as the testicular cell wall and seminiferous tubules disrupted at the higher concentration in a dose‐dependent manner (Figure a–d).…”