Bisphenol A affects early bovine embryo development and metabolism that is negated by an oestrogen receptor inhibitor.

Bom-Ie Choi,Mark P. Green,Alexandra J. Harvey

doi:10.1038/srep29318

Abstract

Increasing evidence supports an association between exposure to endocrine disruptors, such as the xenoestrogen bisphenol A (BPA), a commonly used plasticiser, and the developmental programming of offspring health. To date however animal studies to investigate a direct causal have mainly focussed on supra-environmental BPA concentrations, without investigating the effect on the early embryo. In this study we investigated the effect of acute BPA exposure (days 3.5 to 7.5 post-fertilisation) at environmentally relevant concentrations (1 and 10 ng/mL) on in vitro bovine embryo development, quality and metabolism. We then examined whether culturing embryos in the presence of the oestrogen receptor inhibitor fulvestrant could negate effects of BPA and 17β-oestradiol (E2). Exposure to BPA or E2 (10 ng/mL) decreased blastocyst rate and the percentage of transferrable quality embryos, without affecting cell number, lineage allocation or metabolic gene expression compared to untreated embryos. Notably, blastocysts exposed to BPA and E2 (10 ng/mL) displayed an increase in glucose consumption. The presence of fulvestrant however negated the adverse developmental and metabolic effects, suggesting BPA elicits its effects via oestrogen-mediated pathways. This study demonstrates that even acute exposure to an environmentally relevant BPA concentration can affect early embryo development and metabolism. These may have long-term health consequences on an individual.

Highlights

Endocrine disruptors have begun to receive greater attention in the field of reproductive biology and developmental programming[1,2,3,4]
Length and dose of Bisphenol A (BPA) exposure during pregnancy in animals has begun to be studied. These studies have identified that gestational exposure to a very high BPA concentration (100 mg/kg body weight) severely delays development to the blastocyst stage, completely inhibits implantation[31] and decreases the number of live offspring born in mice[32], studies often fail to measure the exact in vivo BPA concentration to which embryos are exposed in utero
COCs were matured in groups of 50 for 24 h in bicarbonate-buffered TCM199 supplemented with 0.1 IU/mL hCG (Merck Serono), 1 IU/mL recombinant human FSH (Organon), 1 μM cysteamine, 10% (w/v) fetal calf serum (FCS), and 4 mg/mL fatty acid-free bovine serum albumin (FAF-BSA) under embryo-grade mineral oil in Nunc 4-well dishes (Thermo Scientific) at 38.5 °C under 5% CO2 and 20% O2

Summary

Introduction

Endocrine disruptors have begun to receive greater attention in the field of reproductive biology and developmental programming[1,2,3,4]. Bisphenol A (BPA) is one of the most studied endocrine disruptors and one of the highest volume chemicals produced worldwide[5,6,7] This synthetic oestrogen (xenoestrogen) is found in a wide range of everyday products, such as soft plastic bottles, the lining of aluminum food cans and the coating of receipts[5]. Length and dose of BPA exposure during pregnancy in animals has begun to be studied These studies have identified that gestational exposure to a very high BPA concentration (100 mg/kg body weight) severely delays development to the blastocyst stage, completely inhibits implantation[31] and decreases the number of live offspring born in mice[32], studies often fail to measure the exact in vivo BPA concentration to which embryos are exposed in utero. We selected the bovine embryo as it is physiologically similar to the human embryo and has many advantages over the use of rodents for studying the impacts of endocrine disruptors[40,41,42]

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Conclusion