DNA methylation in early mice embryogenesis under the influence of bisphenol A

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Abstract

Background. Nonsteroid estrogen – bisphenol A (BPA) can have a detrimental effect on human health, and therefore poses a potential threat to humans. The critical window for the effect of BPA is the time of early development of the embryo, especially during the activation of the embryonic genome during development to the stage of blastocyst. Therefore, it is especially important to understand how DNA methylation is modified in embryos of the earliest developmental period under the influence of BPA.

Materials and methods. Mice hybrids F1 (CBAXC57BL) were once administered 0, 8 mg of BPA per mouse and the level of DNA methylation was estimated by detection the fluorescence of antibodies against 5-MeC in nuclei of GD3 and GD9 embryos. In other series, the level of DNA methylation and the rate of blastocyst development were estimated following cultivation of one- and two cells embryos in the presence of BPA (50 or 100 µM) during 72-96 hours in vitro.

Results. BPA exposure induced the decrease of the level of DNA methylation in GD3embryos received toxicant in utero, the amount of blastomeres in these embryos was decreased too. The level of DNA methylation in GD9 embryos was slightly higher than in control group. Upon cultivation of one-two cells embryos, BPA decreased the level of DNA methylation and the rate of embryos development to blastocyst stage.

Conclusion. We have determined that early embryogenesis is highly sensitive period to the BPA effects. Such effect is most likely due to active reprogramming processes in this period, primarily related to DNA demethylation/methylation de novo of both the whole genome and individual genes.

About the authors

Ekaterina M. Noniashvili

Institute of Experimental Medicine RAS

Author for correspondence.
Email: katinka.04@list.ru

Cand. of Biol. Sci., senior researcher, Lab. Molecular Cytogenetics of Mammalian Development

Russian Federation, 12, Academic Pavlov street, Saint-Petersburg, 197376

Natalia A. Grudinina

Institute of Experimental Medicine RAS

Email: strangecatnap@gmail.com

Cand. of Biol. Sci., senior researcher, Department of Molecular Genetics

Russian Federation, 12, Academic Pavlov street, Saint-Petersburg, 197376

Marija E. Kustova

Institute of Experimental Medicine RAS

Email: kusmasha@yandex.ru

Cand. of Biol. Sci., senior researcher, Department of Molecular Genetics

Russian Federation, 12, Academic Pavlov street, Saint-Petersburg, 197376

Van Truong Tran

Voronezh State University; Russia-Vietnam research and technological centre

Email: truongleky@gmail.com

PhD student, Department of Biochemistry and Cell Physiology, Voronezh State University, Voronezh, Russia; researcher, Russian-Vietnam research and technological centre

Russian Federation, 1, University square, Voronezh, 394063; Hanoi

Irina O. Suchkova

Institute of Experimental Medicine RAS

Email: irsuchkova@mail.ru

Cand. of Biol. Sci., head researcher, Lab. Molecular Cytogenetics of Mammalian Development

Russian Federation, 12, Academic Pavlov street, Saint-Petersburg, 197376

Larisa I. Pavlinova

Institute of Experimental Medicine RAS

Email: lorhen45@gmail.com

Cand. of Biol. Sci., senior researcher, Lab. Molecular Cytogenetics of Mammalian Development

Russian Federation, 12, Academic Pavlov street, Saint-Petersburg, 197376

Ludmila K. Sasina

Institute of Experimental Medicine RAS

Email: sassinal@gmail.com

Cand. of Biol. Sci., senior researcher, Lab. Molecular Cytogenetics of Mammalian Development

Russian Federation, 12, Academic Pavlov street, Saint-Petersburg, 197376

Natalia I. Dergacheva

Institute of Experimental Medicine RAS

Email: natalia-9999@mail.ru

researcher, Lab. Molecular Cytogenetics of Mammalian Development

Russian Federation, 12, Academic Pavlov street, Saint-Petersburg, 197376

Henrikh A. Sofronov

Institute of Experimental Medicine RAS

Email: gasofronov@mail.ru

academician of RAS, scientific director

Russian Federation, 12, Academic Pavlov street, Saint-Petersburg, 197376

Eugene L. Patkin

Institute of Experimental Medicine RAS

Email: elp44@mail.ru

PhD, Professor. Head, Lab. Molecular Cytogenetics of Mammalian Development

Russian Federation, 12, Academic Pavlov street, Saint-Petersburg, 197376

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2. Fig. 1. The average number of blastomeres in 4-day mouse embryos whose mothers received a single BPA dose (40 mg/kg). The number of embryos studied in each group was: control – 109; sesame oil – 74; BPA – 97. *p = 0,027 (comparisons by t-test) between control/sesame oil groups and BPA group

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3. Fig. 2. The level of fluorescence of antibodies against 5-MeC in nuclei of blastocyst of 4 (а) and 9 day embryos (а) of mice exposed to BPA in utero (single administration to mothers of 40 mg / kg, in vivo). The number of preparations studied in each group was respectively: control – 63 and 51; sesame oil – 42 and 35; BPA – 61 and 39. *p ≤ 0,05 (comparisons by t-test) between control/sesame oil groups and BPA group

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4. Fig. 3. The effect of BPA/ethanol on one-two cell embryos during the cultivation up to the blastocyst stage in vitro for 72-96 hours. The number of embryos studied in each group was: control – 109; ethanol – 152; BPA (50 μM) – 108; BPA (100 μM) – 133. * p ≤ 0.01 between the control/ethanol groups and the BPA groups (comparisons by t-test)

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5. Fig. 5. Changes in the status of DNA methylation in nuclei of mouse embryos of different developmental period under the influence of BPA in vivo (that received BPA in utero) and in vitro (50 μM and 100 μM BPA). *p < 0.01 compared with the control group (comparisons by t-test)

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6. Fig. 4. The level of fluorescence of antibodies against 5-MeC in nuclei of blastocyst developed from one-two cell embryos cultivated with BPA during 76-96 hours. The number of preparations studied in each group was respectively: control – 123; ethanol (0,1 and 0,2 %) – 129 и 148; BPA – 156 и 121 (50 и 100 µМ, respectively). *p < 0.01 between the control/ethanol groups and the BPA groups (comparisons by t-test)

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Copyright (c) 2017 Noniashvili E.M., Grudinina N.A., Kustova M.E., Tran V., Suchkova I.O., Pavlinova L.I., Sasina L.K., Dergacheva N.I., Sofronov H.A., Patkin E.L.

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