 |
 |
 |
 |
 |
 |
Sains Malaysiana
52(5)(2023):
http://doi.org/10.17576/jsm-2023-5205-13
The Impact of Bisphenol A Exposure during Pregnancy on the
Heart of Mother and Fetal Rats
(Kesan Pendedahan Bisfenol A kepada Hati Ibu dan Fetus
Tikus semasa Bunting)
ZATILFARIHIAH
RASDI1, ROZIANA KAMALUDIN2, SITI HAMIMAH SHEIKH ABDUL
KADIR3,4,*, MOHD DANIAL MOHD EFENDY GOON3,4, JESMINE KHAN3,
SHARANIZA AB. RAHIM3 & MOHD HAFIZ DZARFAN OTHMAN2
1Centre of
Preclinical Sciences Studies, Faculty of Dentistry, Universiti Teknologi MARA,
Cawangan Selangor, 47000 Sungai Buloh, Selangor Darul Ehsan, Malaysia
2Advanced
Membrane Technology Research Center (AMTEC), School of Chemical and Energy
Engineering, Universiti Teknologi Malaysia, 81310 UTM Johor Bahru, Johor Darul
Takzim, Malaysia
3Department
of Biochemistry and Molecular Medicine, Faculty of Medicine, Universiti
Teknologi MARA, Cawangan Selangor, 47000 Sungai Buloh, Selangor Darul Ehsan,
Malaysia
4Institute
for Pathology, Laboratory and Forensic Medicine (I-PPerForM), Universiti
Teknologi MARA, Cawangan Selangor, 47000 Sungai Buloh, Selangor Darul Ehsan,
Malaysia
Received: 6 September
2022/Accepted: 29 March 2023
Abstract
In
utero bisphenol A (BPA) exposure has
been reported to increase the risk of cardiovascular disease (CVD) in adult
life. Thus, this study aimed to investigate the impact of in utero BPA
exposure on proteins expression related to cardiac function in heart of rat
foetuses (Rattus norvegicus). In here, pregnant rats were divided into
tween-80 (vehicle control), 0.05 mg/mL and 0.2 mg/mL BPA via drinking water for
19 days: from pregnancy day 2 till 21. Caesarean section was conducted on
pregnancy day 21 to collect plasma and heart of both mother and foetuses.
BPA-exposed pregnant rats showed significant increase in blood pressure (BP)
and reduction in glycogen content (p<0.05) in comparison to control pregnant
rats. Remarkably, reduced expression of cardiac troponin
I (cTnI) and redistribution of alpha fetoprotein (AFP) expression were in
foetus of BPA-exposed mother in comparison with foetus of control mother.
Hypoxia induced factor-1 alpha (HIF-1α) expression was elevated in
BPA-exposed foetal heart compared to the control. The findings in here suggest
the risk of in utero BPA exposure on both foetus and mother, which may
increase the risk of CVD in later life by altering the expression of protein
crucial for heart development and function.
Keywords:
Bisphenol A; cardiovascular disease; foetus; prenatal; protein expression
Abstrak
Pendedahan
bisfenol A (BPA) in utero dilaporkan mampu meningkatkan risiko penyakit
kardiovaskular (CVD). Penyelidikan ini dijalankan untuk mengkaji impak in
utero apabila didedah kepada BPA dari segi ekspresi protein berkait dengan
fungsi kardiak dalam jantung fetus tikus (Rattus norvegicus). Tikus
bunting telah diberi tween-80 (kawalan pembawa), 0.05 mg/mL atau 0.2 mg/mL BPA
melalui air minuman selama 19 hari; dari hari kedua bunting hingga hari ke 21.
Pembedahan Caesarean dijalankan pada hari bunting ke-21 untuk memperoleh plasma
dan jantung daripada fetus dan ibu tikus. Tikus bunting terdedah kepada BPA
menunjukkan kenaikan tekanan darah dan penurunan kandungan glikogen yang ketara
(p<0.05) berbanding kumpulan kawalan tikus bunting. Didapati ekspresi aruhan hipoksia faktor-1
alfa (HIF-1α) meningkat dalam jantung fetus yang
terdedah dengan BPA berbanding kumpulan kawalan. Hasil kajian menunjukkan
risiko pendedahan BPA dalam rahim ke atas fetus dan ibu tikus boleh
meningkatkan risiko penyakit jantung terutamanya dengan peningkatan umur melalui peningkatan
ekspresi protein yang penting dalam perkembangan dan fungsi jantung.
Kata kunci: Bisfenol A; ekspresi
protein; fetus; penyakit kardiovaskular; pranatal
REFERENCES
Adigun, O.O., Yarrarapu, S.N.S., Zubair, M. & Khetarpal,
S. 2019. Alpha Fetoprotein. StatPearls. pp. 8-11. http://www.ncbi.nlm.nih.gov/pubmed/28613501
Allport, S.A., Kikah, N., Saif, N.A., Ekokobe, F.
& Atem, F.D. 2016. Parental age of
onset of cardiovascular disease as a predictor for offspring age of onset of
cardiovascular disease. PLoS ONE 11(12): 1-12. https://doi.org/10.1371/journal.pone.0163334
Bae, S., Kim, J.H., Lim, Y., Park, H.Y. & Hong,
Y. 2012. Associations of bisphenol A
exposure with heart rate variability and blood pressure. Hypertension 60: 786-793.
https://www.ahajournals.org/doi/10.1161/hypertensionaha.112.197715
Barker, D.J. & Osmond, C. 1986. Childhood respiratory infection and adult
chronic bronchitis in England and Wales. British Medical Journal (Clinical Research Ed.), 293(6557):
1271-1275. https://doi.org/10.1136/bmj.294.6564.118
Bondesson, M., Jönsson, J., Pongratz, I., Olea, N., Cravedi, J-P., Zalko, D., Håkansson, H., Halldin, K., Di Lorenzo, D., Behl, C., Manthey, D., Balaguer, P., Demeneix, B., Fini, J.B., Laudet, V. & Gustafsson J-A. 2009. A CASCADE of effects of bisphenol A. Reproductive Toxicology 28: 563-567. https://doi.org/10.1016/j.reprotox.2009.06.014
Białek, S., Górko, D., Zajkowska, A.,
Kołtowski, Ł., Grabowski, M., Stachurska, A., Kochman, J.,
Sygitowicz, G., Małecki, M., Opolski, G. & Sitkiewicz, D. 2015. Release kinetics of circulating miRNA-208a
in the early phase of myocardial infarction. Kardiologia Polska 73(8): 613-619.
https://doi.org/10.5603/KP.a2015.0067
Chapalamadugu, K.C., Vandevoort, C.A., Settles,
M.L., Robison, B.D. & Murdoch, G.K. 2014. Maternal bisphenol A exposure impacts the fetal heart transcriptome. PLoS ONE 9(2): 1-9. https://doi.org/10.1371/journal.pone.0089096
Chapin, R.E., Adams, J., Boekelheide, K., Earl Gray
Jr., L., Hayward, S.W., Lees, P.S.J., McIntyre, B.S., Portier, K.M., Schnorr,
T.M., Selevan, S.G., Vandenbergh, J.G. & Woskie, S.R. 2008. NTP-CERHR expert panel report on the reproductive
and developmental toxicity of bisphenol A. Birth Defects Research
(Part B): Developmental and Productive Toxicology 83(3): 157-395.
Charan, J. & Kantharia, N. 2013. How to calculate sample size in animal
studies? Journal of Pharmacology
and Pharmacotherapeutics 4(4): 303-306.
https://doi.org/10.4103/0976-500X.119726
Chen, M. & Zhang, L. 2011. Epigenetic mechanisms in developmental
programming of adult disease. Drug
Discov. Today 16(23-24): 1007-1018.
https://doi.org/10.1016/j.drudis.2011.09.008.Epigenetic
Chou, W., Chen, J., Lin, C., Chen, Y., Shih, F.
& Chuang, C. 2011. Biomonitoring
of bisphenol A concentrations in maternal and umbilical cord blood in regard to
birth outcomes and adipokine expression: A birth cohort study in Taiwan. Environmental Health 10: 1-10.
Corsten, M.F., Dennert, R., Jochems, S., Kuznetsova,
T., Devaux, Y., Hofstra, L., Wagner, D.R., Staessen, J.A., Heymans, S. &
Schroen, B. 2010. Circulating MicroRNA-208b and MicroRNA-499 reflect myocardial
damage in cardiovascular disease. Circulation: Cardiovascular Genetics 3(6): 499-506. https://doi.org/10.1161/CIRCGENETICS.110.957415
Corvino, S.B., Volpato, G.T., Macedo, N.C.D.,
Sinzato, Y.K., Rudge, M.V.C. & Damasceno, D.C. 2015. Physiological and biochemical measurements
before, during and after pregnancy of healthy rats. Acta Cirurgica Brasileira 30(10): 668-674.
https://doi.org/10.1590/S0102-865020150100000003
Dawes, G.S., Mott, J.C. & Shelley, H.J. 1959. The importance of cardiac glycogen for the
maintenance of life in foetal lambs and new-born animals during anoxia. The Journal of Physiology 146(3):
516-538.
De Mees, C., Bakker, J., Szpirer, J. & Szpirer,
C. 2017. Alpha-fetoprotein: From a
diagnostic biomarker to a key role in female fertility. Biomarker Insights 1: 117727190600100.
https://doi.org/10.1177/117727190600100002
DiVall, S.A. 2013. The influence of endocrine disruptors on growth and development of
children. Current Opinion in
Endocrinology, Diabetes and Obesity 20(1): 50-55.
https://doi.org/10.1097/MED.0b013e32835b7ee6
Doerge, D.R., Twaddle, N.C., Vanlandingham, M.,
Brown, R.P. & Fisher, J.W. 2011. Distribution
of bisphenol A into tissues of adult, neonatal, and fetal Sprague - Dawley rats. Toxicology and Applied Pharmacology 255: 261-270. https://doi.org/10.1016/j.taap.2011.07.009
Fern, C., Gonz, S., Navarro, C. & Lomb, M. 2015. Transgenerational inheritance of heart
disorders caused by paternal bisphenol A exposure. Environmental Pollution 206: 667-678.
Gj, M. 2019. Protein
binding and interactions with alpha-fetoprotein (AFP): A review of multiple AFP
cell surface receptors, intracytoplasmic binding, and inter- molecular
complexing proteins. Journal of
Molecular and Cellular Biology Forecast 2: 1-8.
Gray, C., Li, M., Patel, R., Reynolds, C.M. &
Vickers, M.H. 2014. Let-7 miRNA profiles are associated with the reversal of
left ventricular hypertrophy and hypertension in adult male offspring from
mothers undernourished during pregnancy after preweaning growth hormone treatment. Endocrinology 155(12): 4808-4817. https://doi.org/10.1210/en.2014-1567
Hain, A.M. 1932. Increase in weight of the mother
and of the foetus during pregnancy (rat). Quarterly Journal of Experimental
Physiology 22(1): 71-78. https://doi.org/10.1113/expphysiol.1932.sp000560
Han, C. & Hong, Y. 2016. Bisphenol A,
hypertension, and cardiovascular diseases: Epidemiological, laboratory, and
clinical trial evidence. Curr. Hypertens Rep. 11(18): 1-5.
https://doi.org/10.1007/s11906-015-0617-2
Hijazi, A., Guan, H., Cernea, M. & Yang, K.
2015. Prenatal exposure to bisphenol A disrupts mouse fetal lung development. The
FASEB 29: 4968-4977. https://doi.org/10.1096/fj.15-270942
Huang, X., Ding, L., Bennewith, K.L., Tong, R.T.,
Welford, S.M., Ang, K.K., Story, M., Le, Q.T. & Giaccia, A.J. 2009.
Hypoxia-inducible mir-210 regulates normoxic gene expression involved in tumor
initiation. Molecular Cell. https://doi.org/10.1016/j.molcel.2009.09.006
Ikezuki, Y., Tsutsumi, O., Takai, Y., Kamei, Y.
& Taketani, Y. 2002. Determination of bisphenol A concentrations in human
biological fluids reveals significant early prenatal exposure. Human
Reproduction 17(11): 2839-2841. https://doi.org/10.1093/humrep/17.11.2839
Kawanabe, Y. & Nauli, S.M. 2011. Endothelin. Cell
Mol. Life Sci. 68(2): 195-203. https://doi.org/10.1161/CIRCULATIONAHA.110.956839
Martínez, M.A., Rovira, J., Sharma, R.P., Nadal, M.,
Schuhmacher, M. & Kumar, V. 2017. Prenatal exposure estimation of BPA and
DEHP using integrated external and internal dosimetry: A case study. Environmental
Research 158: 566-575. https://doi.org/10.1016/j.envres.2017.07.016
Momtahan, N., Crosby, C.O. & Zoldan, J. 2019.
The role of reactive oxygen species in in vitro cardiac maturation. Trends
in Molecular Medicine 25(6): 482-493.
https://doi.org/10.1016/j.molmed.2019.04.005
Mushtaque, R.S., Hameed, S., Mushtaque, R., Idrees,
M. & Siraj, F. 2019. Role of cardio-specific micro-ribonucleic acids and
correlation with cardiac biomarkers in acute coronary syndrome: A comprehensive
systematic review. Cureus 11(10): e5878. https://doi.org/10.7759/cureus.5878
Nahon, J.L., Tratner, I., Poliard, A., Presse, F.,
Poiret, M., Gal, A., Sala-Trepat, J.M., Legres, l., Feldmann, G. & Bernuau,
D. 1988. Albumin and α-fetoprotein gene expression in various nonhepatic
rat tissues. Journal of Biological Chemistry 263(23): 11436-11442.
Nakamura, K., Itoh, K., Yoshimoto, K., Sugimoto, T.
& Fushiki, S. 2010. Prenatal and lactational exposure to low doses of
bisphenol A alters brain monoamine concentration in adult mice. Neuroscience
Letters 484: 66-70. https://doi.org/10.1016/j.neulet.2010.08.021
Nwachukwu, D., Adegunloye, B.J. & Bello, O.I.
2001. Blood pressure and heart rate changes during pregnancy in fructose-fed
sprague-dawley. Afr. J. Med. Sci. 30: 187-190.
http://www.unn.edu.ng/publications/files/NWACHUKWU_D_C_2.pdf
Palinski, W. & Napoli, C. 2008. Impaired fetal
growth, cardiovascular disease, and the need to move on. Circulation 117(3): 341-343. https://doi.org/10.1161/CIRCULATIONAHA.107.750133
Paronis, E., Samara, A., Polyzos, A., Spyropoulos,
C. & Kostomitsopoulos, N.G. 2015. Maternal weight as an alternative
determinant of the gestational day of Wistar rats housed in individually
ventilated cages. Laboratory Animals 49(3): 188-195.
https://doi.org/10.1177/0023677214562846
Pederson, B.A., Chen, H., Schroeder, J.M., Shou, W.,
DePaoli-Roach, A.A. & Roach, P.J. 2004. Abnormal cardiac development in the
absence of heart glycogen. Molecular and Cellular Biology 24(16):
7179-7187. https://doi.org/10.1128/mcb.24.16.7179-7187.2004
Rasdi, Z., Kamaludin, R., Ab. Rahim, S., Syed Ahmad
Fuad, S.B., Othman, M.H.D., Siran, R., Mohd Nor, N.S., Abdul Hamid Hasani, N.
& Sheikh Abdul Kadir, S.H. 2020. The impacts of intrauterine Bisphenol A
exposure on pregnancy and expression of miRNAs related to heart development and
diseases in animal model. Scientific Reports 10: 5882. DOI: 10.1038/s41598-020-62420-1
Ravichandran, J., Woon, S.Y., Quek, Y.S., Lim, Y.C.,
Noor, E.M., Suresh, K., Vigneswaran, R., Vasile, V., Shah, A., Mills, N.L.,
Sickan, J., Beshiri, A. & Jaffe, A.S. 2019. High-sensitivity cardiac
troponin I levels in normal and hypertensive pregnancy. American Journal of
Medicine 132(3): 362-366. https://doi.org/10.1016/j.amjmed.2018.11.017
Ritterhoff, J. & Tian, R. 2017. Metabolismin
cardiomyopathy: Every substrate matters. Cardiovascular Research 113(4):
411-421. https://doi.org/10.1093/cvr/cvx017
Schönfelder, G., Flick, B., Mayr, E., Talsness, C.,
Paul, M. & Chahoud, I. 2002. In utero exposure to low doses of
bisphenol A led to long-term deleterious effects in the vagina. Neoplasia 4(2): 98-102. https://doi.org/10.1038/sj/neo/7900212
Shankar, A., Teppala, S. & Sabanayagam, C.
2012a. Bisphenol A and peripheral arterial disease: Results from the NHANES. Environmental
Health Perspectives 120(9): 1297-1300. https://doi.org/10.1289/ehp.1104114
Szablewski, L. 2017. Glucose transporters in healthy
heart and in cardiac disease. International Journal of Cardiology 230:
70-75. https://doi.org/10.1016/j.ijcard.2016.12.083
Tan, B.L.L.L., Mohd, M.A. & Ali Mohd, M. 2003.
Analysis of selected pesticides and alkylphenols in human cord blood by gas
chromatograph-mass spectrometer. Talanta 61(3): 385-391.
https://doi.org/10.1016/S0039-9140(03)00281-9
Tin, L.L., Beevers, D.G. & Lip, G.Y.H. 2002.
Systolic vs diastolic blood pressure and the burden of hypertension. Journal
of Human Hypertension 16(3): 147-150.
https://doi.org/10.1038/sj.jhh.1001373
Tong, W., Xue, Q., Li, Y. & Zhang, L. 2011.
Maternal hypoxia alters matrix metalloproteinase expression patterns and causes
cardiac remodeling in fetal and neonatal rats. American Journal of
Physiology - Heart and Circulatory Physiology 301(5): H2113-H2121. https://doi.org/10.1152/ajpheart.00356.2011
Vandenberg, L.N., Colborn, T., Hayes, T.B., Heindel,
J.J., Jacobs, D.R., Lee, D.H., Shioda, T., Soto, A.M., vom Saal, F.S.,
Welshons, W.V., Zoeller, R.T. & Myers, J.P. 2012. Hormones and
endocrine-disrupting chemicals: Low-dose effects and nonmonotonic dose
responses. Endocrine Reviews 33(3): 378-455.
https://doi.org/10.1210/er.2011-1050
Vettori, S., Gay, S. & Distler, O. 2012. Role of
MicroRNAs in fibrosis. The Open Rheumatology 6: 130-139.
Vo, W., Colnot, T., Csana, A., Filser, J.G., Dekant,
W., Völkel, W., Colnot, T., Csanády, G.A., Filser, J.G. & Dekant, W. 2002.
Metabolism and kinetics of bisphenol a in humans at low doses following oral
administration. Chemical Research in Toxicology 15(10): 1281-1287.
https://doi.org/10.1021/tx025548t
Wang, G., Chen, Z., Bartell, T. & Wang, X. 2014.
Early life origins of metabolic syndrome: The role of environmental toxicants. Current
Environmental Health Reports 1(1): 78-89. https://doi.org/10.1007/s40572-013-0004-6
Yan, I., Börschel, C.S., Neumann, J.T., Sprünker,
N.A., Makarova, N., Kontto, J., Kuulasmaa, K., Salomaa, V., Magnussen, C.,
Iacoviello, L., Di Castelnuovo, A., Costanzo, S., Linneberg, A., Söderberg, S.,
Zeller, T., Ojeda-Echevarria, F.M., Blankenberg, S. & Westermann, D. 2020.
High-sensitivity cardiac troponin I levels and prediction of heart failure. JACC:
Heart Failure 8(5): 401-411. https://doi.org/10.1016/j.jchf.2019.12.008
Yang, X., Doerge, D.R. & Fisher, J.W. 2013.
Prediction and evaluation of route dependent dosimetry of BPA in rats at
different life stages using a physiologically based pharmacokinetic model. Toxicology
and Applied Pharmacology 270(1): 45-59.
https://doi.org/10.1016/j.taap.2013.03.022
Zanto, T.P., Hennigan, K., Östberg, M., Clapp, W.C.
& Gazzaley, A. 2011. Defining normal and abnormal fetal growth: Promises
and challenges. American Journal of Obstetrics & Gynecology 46(4):
564-574. https://doi.org/10.1016/j.cortex.2009.08.003.Predictive
Zhang, H., Yao, M., Morrison, R.A. & Chong, S.
2003. Commonly used surfactant, Tween 80, improves absorption of P-glycoprotein
substrate, digoxin, in rats. Archives of Pharmacal Research 26(9):
768-772. https://doi.org/10.1007/BF02976689
*Corresponding author; email: sitih587@uitm.edu.my
|
|||
|
