The influence of exogenic lactoferrin on DNA methylation in postimplantation mouse embryos developed from zygotes exposed to bisphenol A

Abstract

BACKGROUND: Bisphenol A is a chemical agent ubiquitous in plastic consumer products and a toxin capable of disrupting key epigenetic mechanisms in early embryogenesis. It becomes more and more clear that early development changes in epigenetic pathways caused by exposure to toxic substances are associated with various adult diseases. Therefore the need to identify new agents capable of eliminating epigenetic mechanisms failures caused by the bisphenol A toxin becomes evident. Here we suggest lactoferrin as a normalizer of toxicant-induced epigenomic changes. Currently there is no data on the role of lactoferrin as a normalizer of epigenomic disorders under the influence of toxicants. We assume that in mammalian embryogenesis lactoferrin might function as an epigenetic modulating factor.

AIM: The aim of the research is to study effects of lactoferrin on the epigenetic status of postimplantation mouse embryos, exposed to bisphenol A in utero.

MATERIALS AND METHODS: In this study, 3 experimental groups of mice and two control group were used. 1. Mice on the first day of pregnancy, injected with 40 mg/kg of body weight of bisphenol A; 2. Mice on the first day of pregnancy, injected with 50 mg/kg of body weight of lactoferrin; 3. Mice on the first day of pregnancy, successively injected with 50 mg/kg body weight of lactoferrin and 40 mg/kg of body weight of bisphenol A. On the 15^th day of embryonic development, the level of genome-wide DNA methylation was evaluated in different body parts of the embryos by methyl-sensitive restriction and ImageJ visualization analysis.

RESULTS: We demonstrated that in post-implantation mouse embryos, exposure to bisphenol A in the prenatal period caused an increased level of genome-wide DNA methylation. The most prominent effects were observed in brain and abdominal section of the embryos. Together, the present findings confirmed that lactoferrin administration at a dose of 50 mg/kg of body weight resulted in normalization of genome-wide DNA methylation levels after bisphenol A-induced epigenetic alterations.

CONCLUSIONS: We assume that lactoferrin may partially neutralize the harmful effects of bisphenol A caused aberrant methylation, and thus can potentially be used as a pharmaceutical product. Factual findings of the present study may help by development of new therapeutic approaches. Nevertheless, further research of the bisphenol A, lactoferrin and lactoferrin + bisphenol A effects on reactive oxygen species and/or antioxidant enzymes is needed.

Keywords

bisphenol A / DNA methylation / epigenetic disorders / lactoferrin / postimplantation mouse embryo

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