The influence of exogenic lactoferrin on DNA methylation in postimplantation mouse embryos developed from zygotes exposed to bisphenol A
- Authors: Postnikova L.A.1, Noniashvili E.M.1, Suchkova I.O.1, Baranova T.V.1, Patkin E.L.1
-
Affiliations:
- Institute of Experimental Medicine
- Issue: Vol 22, No 4 (2022)
- Pages: 45-56
- Section: Original research
- URL: https://journals.eco-vector.com/MAJ/article/view/109416
- DOI: https://doi.org/10.17816/MAJ109416
- ID: 109416
Cite item
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 15th 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.
Full Text
About the authors
Liubov A. Postnikova
Institute of Experimental Medicine
Email: ofeliyafutman@gmail.com
ORCID iD: 0000-0003-3306-8266
SPIN-code: 6191-7966
ResearcherId: HGB-3000-2022
Master of Biology, PhD student, Junior Research Associate, Laboratory of Molecular Cytogenetics of Mammalian Development, Department of Molecular Genetics
Russian Federation, Saint PetersburgEkaterina M. Noniashvili
Institute of Experimental Medicine
Email: katinka.04@list.ru
ORCID iD: 0000-0002-2347-6920
SPIN-code: 1799-7736
Scopus Author ID: 6602403829
ResearcherId: E-4173-2014
Саnd. Sci. (Biol.), Senior Research Associate, Laboratory of Molecular Cytogenetics of Mammalian Development, Department of Molecular Genetics
Russian Federation, Saint PetersburgIrina O. Suchkova
Institute of Experimental Medicine
Email: irsuchkova@mail.ru
ORCID iD: 0000-0003-2127-0459
SPIN-code: 4155-7314
Scopus Author ID: 6602838276
ResearcherId: H-4484-2014
Cand. Sci. (Biol.), Senior Research Associate, Laboratory of Molecular Cytogenetics of Mammalian Development, Department of Molecular Genetics
Russian Federation, Saint PetersburgTatyana V. Baranova
Institute of Experimental Medicine
Email: tanjabaranova@mail.ru
ORCID iD: 0000-0002-8269-8881
SPIN-code: 1356-1402
Scopus Author ID: 57205972796
Cand. Sci. (Biol.), Junior Research Associate, Laboratory of Molecular Cytogenetics of Mammalian Development, Department of Molecular Genetics
Russian Federation, Saint PetersburgEugene L. Patkin
Institute of Experimental Medicine
Author for correspondence.
Email: elp44@mail.ru
ORCID iD: 0000-0002-6292-4167
SPIN-code: 4929-4630
Scopus Author ID: 7003713993
ResearcherId: J-7779-2013
Dr. Sci. (Biol.), Professor, Head of Laboratory of Molecular Cytogenetics of Mammalian Development, Department of Molecular Genetics
Russian Federation, Saint PetersburgReferences
- Bateson P, Barker D, Clutton-Brock T, et al. Developmental plasticity and human health. Nature. 2004;430(6998):419–421. doi: 10.1038/nature02725
- Bernal AJ, Jirtle RL. Epigenomic disruption: the effects of early developmental exposures. Birth Defects Res A Clin Mol Teratol. 2010;88(10):938–944. doi: 10.1002/bdra.20685
- Dolinoy DC, Huang D, Jirtle RL. Maternal nutrient supplementation counteracts bisphenol A-induced DNA hypomethylation in early development. Proc Natl Acad Sci USA. 2007;104(32):13056–13061. doi: 10.1073/pnas.0703739104
- Vom Saal FS, Akingbemi BT, Belcher SM, et al. Chapel Hill bisphenol A expert panel consensus statement: integration of mechanisms, effects in animals and potential to impact human health at current levels of exposure. Reprod Toxicol. 2007;24(2):131–138. doi: 10.1016/j.reprotox.2007.07.005
- Kim JH, Sartor MA, Rozek LS, et al. Perinatal bisphenol A exposure promotes dose-dependent alterations of the mouse methylome. BMC Genomics. 2014;15:30. doi: 10.1186/1471-2164-15-30
- Lee YM, Seong MJ, Lee JW, et al. Estrogen receptor independent neurotoxic mechanism of bisphenol A, an environmental estrogen. J Vet Sci. 2007;8(1):27–38. doi: 10.4142/jvs.2007.8.1.27
- Gassman NR. Induction of oxidative stress by bisphenol A and its pleiotropic effects. Environ Mol Mutagen. 2017;58(2):60–71. doi: 10.1002/em.22072
- El Henafy HMA, Ibrahim MA, Abd El Aziz SA, Gouda EM. Oxidative stress and DNA methylation in male rat pups provoked by the transplacental and translactational exposure to bisphenol A. Environ Sci Pollut Res Int. 2020;27(4):4513–4519. doi: 10.1007/s11356-019-06553-5
- Weng YI, Hsu PY, Liyanarachchi S, et al. Epigenetic influences of low-dose bisphenol A in primary human breast epithelial cells. Toxicol Appl Pharmacol. 2010;248(2):111–121. doi: 10.1016/j.taap.2010.07.014
- Postnikova LA, Patkin EL. The possible effect of lactoferrin on the epigenetic characteristics of early mammalian embryos exposed to bisphenol A. Birth Defects Res. 2022;114(19):1199–1209. doi: 10.1002/bdr2.2017
- Legrand D, Pierce A, Elass E, et al. Lactoferrin structure and functions. Adv Exp Med Biol. 2008;606:163–194. doi: 10.1007/978-0-387-74087-4_6
- Teng CT, Beard C, Gladwell W. Differential expression and estrogen response of lactoferrin gene in the female reproductive tract of mouse, rat, and hamster. Biol Reprod. 2002;67(5):1439–1449. doi: 10.1095/biolreprod.101.002089
- Teng CT, Gladwell W, Beard C, et al. Lactoferrin gene expression is estrogen responsive in human and rhesus monkey endometrium. Mol Hum Reprod. 2002;8(1):58–67. doi: 10.1093/molehr/8.1.58
- Ward PP, Paz E, Conneely OM. Multifunctional roles of lactoferrin: a critical overview. Cell Mol Life Sci. 2005;62(22):2540–2548. doi: 10.1007/s00018-005-5369-8
- Zakharova ET, Kostevich VA, Sokolov AV, Vasilyev VB. Human apo-lactoferrin as a physiological mimetic of hypoxia stabilizes hypoxia-inducible factor-1 alpha. Biometals. 2012;25(6):1247–1259. doi: 10.1007/s10534-012-9586-y
- Reale E, Taverna D, Cantini L, et al. Investigating the epi-miRNome: identification of epi-miRNAs using transfection experiments. Epigenomics. 2019;11(14):1581–1599. doi: 10.2217/epi-2019-0050
- Zhang TN, Liu N. Effect of bovine lactoferricin on DNA methyltransferase 1 level in Jurkat T-leukemia cells. J Dairy Sci. 2010;93(9):3925–3930. doi: 10.3168/jds.2009-3024
- Lebedev DV, Zabrodskaya YA, Pipich V, et al. Effect of alpha-lactalbumin and lactoferrin oleic acid complexes on chromatin structural organization. Biochem Biophys Res Commun. 2019;520(1):136–139. doi: 10.1016/j.bbrc.2019.09.116
- Safaeian L, Zabolian H. Antioxidant effects of bovine lactoferrin on dexamethasone-induced hypertension in the rat. ISRN Pharmacol. 2014;2014:943523. doi: 10.1155/2014/943523
- Verduci E, Banderali G, Barberi S, et al. Epigenetic effects of human breast milk. Nutrients. 2014;6(4):1711–1724. doi: 10.3390/nu6041711
- Medrano JV, Pera RA, Simón C. Germ cell differentiation from pluripotent cells. Semin Reprod Med. 2013;31(1):14–23. doi: 10.1055/s-0032-1331793
- Sukjamnong S, Thongkorn S, Kanlayaprasit S, et al. Prenatal exposure to bisphenol A alters the transcriptome-interactome profiles of genes associated with Alzheimer’s disease in the offspring hippocampus. Sci Rep. 2020;10(1):9487. doi: 10.1038/s41598-020-65229-0
- Nahar MS, Liao C, Kannan K, et al. In utero bisphenol A concentration, metabolism, and global DNA methylation across the matched placenta, kidney, and liver in the human fetus. Chemosphere. 2015;124:54–60. doi: 10.1016/j.chemosphere.2014.10.071
- Quan C, Wang C, Duan P, et al. Prenatal bisphenol exposure leads to reproductive hazards on male offspring via the Akt/mTOR and mitochondrial apoptosis pathways. Environ Toxicol. 2017;32(3):1007–1023. doi: 10.1002/tox.22300
- Cagampang FR, Torrens C, Anthony FW, Hanson MA. Developmental exposure to bisphenol A leads to cardiometabolic dysfunction in adult mouse offspring. J Dev Orig Health Dis. 2012;3(4):287–292. doi: 10.1017/S2040174412000153
- Boronat-Belda T, Ferrero H, Al-Abdulla R, et al. Bisphenol-A exposure during pregnancy alters pancreatic β-cell division and mass in male mice offspring: A role for ERβ. Food Chem Toxicol. 2020;145:111681. doi: 10.1016/j.fct.2020.111681
- Song Y, Hauser R, Hu FB, et al. Urinary concentrations of bisphenol A and phthalate metabolites and weight change: a prospective investigation in US women. Int J Obes (Lond). 2014;38(12):1532–1537. doi: 10.1038/ijo.2014.63
- Donohue KM, Miller RL, Perzanowski MS, et al. Prenatal and postnatal bisphenol A exposure and asthma development among inner-city children. J Allergy Clin Immunol. 2013;131(3):736–742. doi: 10.1016/j.jaci.2012.12.1573
- Babu S, Uppu S, Claville MO, Uppu RM. Prooxidant actions of bisphenol A (BPA) phenoxyl radicals: implications to BPA-related oxidative stress and toxicity. Toxicol Mech Methods. 2013;23(4):273–280. doi: 10.3109/15376516.2012.753969
- Meli R, Monnolo A, Annunziata C, et al. Oxidative stress and BPA toxicity: an antioxidant approach for male and female reproductive dysfunction. Antioxidants (Basel). 2020;9(5):405. doi: 10.3390/antiox9050405
- Leem YH, Oh S, Kang HJ, et al. BPA-toxicity via superoxide anion overload and a deficit in β-catenin signaling in human bone mesenchymal stem cells. Environ Toxicol. 2017;32(1):344–352. doi: 10.1002/tox.22239
- Kobayashi K, Liu Y, Ichikawa H, et al. Effects of Bisphenol A on oxidative stress in the rat brain. Antioxidants (Basel). 2020;9(3):240. doi: 10.3390/antiox9030240
- Severson PL, Tokar EJ, Vrba L, et al. Agglomerates of aberrant DNA methylation are associated with toxicant-induced malignant transformation. Epigenetics. 2012;7(11):1238–1248. doi: 10.4161/epi.22163
- Warita K, Mitsuhashi T, Ohta K, et al. Gene expression of epigenetic regulatory factors related to primary silencing mechanism is less susceptible to lower doses of bisphenol A in embryonic hypothalamic cells. J Toxicol Sci. 2013;38(2):285–289. doi: 10.2131/jts.38.285
- Ahmed RG, Walaa GH, Asmaa FS. Suppressive effects of neonatal bisphenol A on the neuroendocrine system. Toxicol Ind Health. 2018;34(6):397–407. doi: 10.1177/0748233718757082
- Dinant C, Luijsterburg MS. The emerging role of HP1 in the DNA damage response. Mol Cell Biol. 2009;29(24):6335–6340. doi: 10.1128/MCB.01048-09
- Eckersley-Maslin MA, Alda-Catalinas C, Reik W. Dynamics of the epigenetic landscape during the maternal-to-zygotic transition. Nat Rev Mol Cell Biol. 2018;19(7):436–450. doi: 10.1038/s41580-018-0008-z
- Hayes P, Knaus UG. Balancing reactive oxygen species in the epigenome: NADPH oxidases as target and perpetrator. Antioxid Redox Signal. 2013;18(15):1937–1945. doi: 10.1089/ars.2012.4895
- Campos AC, Molognoni F, Melo FH, et al. Oxidative stress modulates DNA methylation during melanocyte anchorage blockade associated with malignant transformation. Neoplasia. 2007;9(12):1111–1121. doi: 10.1593/neo.07712
- Hitchler MJ, Domann FE. An epigenetic perspective on the free radical theory of development. Free Radic Biol Med. 2007;43(7):1023–1036. doi: 10.1016/j.freeradbiomed.2007.06.027
- Patkin EL, Grudinina NA, Sasina LK, et al. DNA methylation differs between sister chromatids, and this difference correlates with the degree of differentiation potential. Mol Reprod Dev. 2015;82(10):724–725. doi: 10.1002/mrd.22519
- Richardson BE, Lehmann R. Mechanisms guiding primordial germ cell migration: strategies from different organisms. Nat Rev Mol Cell Biol. 2010;11(1):37–49. doi: 10.1038/nrm2815
- Saitou M, Yamaji M. Primordial germ cells in mice. Cold Spring Harb Perspect Biol. 2012;4(11):a008375. doi: 10.1101/cshperspect.a008375
- Stouder C, Paoloni-Giacobino A. Transgenerational effects of the endocrine disruptor vinclozolin on the methylation pattern of imprinted genes in the mouse sperm. Reproduction. 2010;139(2):373–379. doi: 10.1530/REP-09-0340
- Lange UC, Schneider R. What an epigenome remembers. Bioessays. 2010;32(8):659–668. doi: 10.1002/bies.201000030
- Wang L, Zhang J, Duan J, et al. Programming and inheritance of parental DNA methylomes in mammals. Cell. 2014;157(4):979–991. doi: 10.1016/j.cell.2014.04.017