The toxic effects and possible mechanisms of Bisphenol A on oocyte maturation of porcine in vitro.

Teng Wang,Xing Duan,Bo Xiong,Xiang-Shun Cui,Hong-Lin Liu,Nam-Hyung Kim,Shao-Chen Sun,Jun Han

doi:10.18632/oncotarget.8689

Teng Wang, Xing Duan + Show 6 more

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https://doi.org/10.18632/oncotarget.8689

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Abstract

Bisphenol A (BPA) and Di-(2-ethylhexyl) phthalate (DEHP) are widely used in the plastic industry such as water bottles, containers, packaging and toys. BPA and DEHP are shown to be the endocrine disruptors which disturb the endocrine system and are linked to several diseases including infertility. In this study, we investigated the effects of BPA exposure on porcine oocyte maturation and its possible reasons. Our results showed that: (i) the rates of oocyte maturation significantly decreased with 250 μM BPA treatment in vitro, but not DEHP. This might be due to the delayed cell cycle progression of oocyte maturation. (ii) BPA treatment resulted in abnormal cytoskeletons on porcine oocytes, showing with aberrant actin distribution, spindle morphology and chromosome alignment, which was further confirmed by the reduced p-MAPK level. (iii) The fluorescence intensity of histone methylation (H3K4me2) and DNA methylation (5 mC) levels were altered after BPA treatment, indicating that epigenetic modification was disturbed. (iv) BPA-exposed oocytes had higher rates of early stage apoptosis/autophagy, and this may be resulted from the increased level of oxidative stress. Collectively, our results indicated that porcine oocytes maturation was disrupted after BPA treatment through disrupting cytoskeletal dynamics, epigenetic modifications and inducing apoptosis/autophagy.

Highlights

The growing evidence indicates that environmental contaminants can pose negatively risks to animals and human health
To find the causes and mechanism for toxic effects of Bisphenol A (BPA) exposure on oocytes, we investigated this through epigenetic modification and apoptosis/autophagy aspects with the porcine model, since the genome of porcine is more close to human species, which could more concisely reflect the reproduction system of human
Our results indicated that exposure to BPA caused failure of polar body extrusion on porcine oocytes in vitro, but not Di-(2-ethylhexyl) phthalate (DEHP)

Summary

Introduction

The growing evidence indicates that environmental contaminants can pose negatively risks to animals and human health. Because some of these substances can mimic and alter the actions of endogenous hormones, some potentially disrupting endocrine function in humans thereby they are referred to as endocrine disruptors (EDC) [1, 2]. Di(2-ethylhexyl) phthalate (diethyl-hexyl phthalate, DEHP) is widely used as a plasticizer in manufacturing products made by polyvinyl compounds, and it is an estrogen-like chemical [3, 4]. To DEHP, Bisphenol A (BPA) is a high production volume environmental estrogen-like chemical, and it is widely used in a variety of manufacturing polycarbonate plastic products posing a risk health to human [3]. In 2010, Canada is the first country that announced BPA is a toxic substance, and the European Union, Canada and the United States have banned BPA in baby bottles

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