The use of artificial sweeteners as non-nutritive food additive is becoming very common nowadays. The aim of this research was to study the effect of commercial artificial sweeteners consumption on the adult mouse mammary gland in pregnancy (18-day pregnancy) and 3 weeks nursing. A commercial artificial sweetener solution was given to pregnant mice of treated groups 50 mg/kg body weight, from day one of pregnancy till the end of 3 weeks nursing. Controls were given distilled water. The histological studies of the mammary gland of treated animals showed some changes. In treated 18-day pregnant mothers; the amount of adipose cells seemed to increase and the amount of lipid droplets within the alveoli seemed to increase compared to the controls. Also alveoli in the treated mammary gland sections appeared to be larger and less in number compared to the controls. In 3 weeks treated nursing mothers the amount of milk and lipid droplets in the alveoli decreased compared to the controls. The mammary gland circumference of treated 18-day pregnant mothers was significantly smaller compared to the controls, while it was significantly larger in 3 weeks treated nursing mothers compared to the controls. These results show that artificial sweeteners disturbed the arrangement of the histological structure in the mammary gland of pregnant and nursing mice. Awareness should be raised to restrict the use of artificial sweeteners to people with diabetes or who are in medical need.
References
[1]
Islam, M.S. and Sakaguchi, E. (2006) Sorbitol-Based Osmotic Diarrhea: Possible Causes and Mechanism of Prevention Investigated in Rats. World Journal of Gastroenterology: WJG, 12, 7635. https://doi.org/10.3748/wjg.v12.i47.7635
[2]
Mourad, I.M. and Noor, N.A. (2011) Aspartame (A Widely Used Artificial Sweetener) and Oxidative Stress in the Rat Cerebral Cortex. Journal of Pharmaceutical and Biomedical Sciences, 2, 4-10.
[3]
Ozen, I.T., Karav, S. and Eksi, A. (2014) Variability of Sorbitol/Xylitol Content in Pomegranate (Punica granatum) Juice as Affected by Processing Conditions. International Journal of Food and Nutrition Science, 3, 4-7.
[4]
Siripurkpong, P., et al. (2014) Sorbitol Has No Significant Effects on 3T3-L1-Adipogenesis and Adiponectin Synthesis and Secretion. Science & Technology Asia, 19, 64-73.
[5]
Washburn, C. and Christensen, N. (2012) Sugar Substitutes: Artificial Sweeteners and Sugar Alcohols.
[6]
Whitehouse, C.R., Boullata, J. and McCauley, L.A. (2008) The Potential Toxicity of Artificial Sweeteners. AAOHN Journal, 56, 251-261. https://doi.org/10.1177/216507990805600604
[7]
Iyyaswamy, A. and Rathinasamy, S. (2012) Effect of Chronic Exposure to Aspartame on Oxidative Stress in Brain Discrete Regions of Albino Rats. Journal of Biosciences, 37, 679-688. https://doi.org/10.1007/s12038-012-9236-0
[8]
Ramadan, G.A. (2007) Sorbitol-Induced Diabetic-Like Retinal Lesions in Rats: Microscopic Study. American Journal of Pharmacology and Toxicology, 2, 89-97. https://doi.org/10.3844/ajptsp.2007.89.97
[9]
Ota, A., et al. (2013) Effects of Long-Term Treatment with Ranirestat, a Potent Aldose Reductase Inhibitor, on Diabetic Cataract and Neuropathy in Spontaneously Diabetic Torii Rats. Journal of Diabetes Research, 2013, Article ID: 175901. https://doi.org/10.1155/2013/175901
[10]
Hedrich, H. (2004) The Laboratory Mouse. Academic Press, Cambridge.
[11]
Hassiotou, F. and Geddes, D. (2013) Anatomy of the Human Mammary Gland: Current Status of Knowledge. Clinical Anatomy, 26, 29-48. https://doi.org/10.1002/ca.22165
[12]
Sordillo, L., Shafer-Weaver, K. and DeRosa, D. (1997) Immunobiology of the Mammary Gland. Journal of Dairy Science, 80, 1851-1865. https://doi.org/10.3168/jds.S0022-0302(97)76121-6
[13]
Vorbach, C., Capecchi, M.R. and Penninger, J.M. (2006) Evolution of the Mammary Gland from the Innate Immune System? Bioessays, 28, 606-616. https://doi.org/10.1002/bies.20423
[14]
Watson, C.J. (2006) Key Stages in Mammary Gland Development-Involution: Apoptosis and Tissue Remodelling That Convert the Mammary Gland from Milk Factory to a Quiescent Organ. Breast Cancer Research, 8, 203. https://doi.org/10.1186/bcr1401
[15]
Richert, M.M., et al. (2000) An Atlas of Mouse Mammary Gland Development. Journal of Mammary Gland Biology and Neoplasia, 5, 227-241. https://doi.org/10.1023/A:1026499523505
[16]
Hennighausen, L. and Robinson, G.W. (2005) Information Networks in the Mammary Gland. Nature Reviews Molecular Cell Biology, 6, 715-725. https://doi.org/10.1038/nrm1714
[17]
Capuco, A.V. and Akers, R.M. (2009) Management and Environmental Influences on Mammary Gland Development and Milk Production. In: Managing the Prenatal Environment to Enhance Livestock Productivity, Springer, Berlin, 259-292. https://doi.org/10.1007/978-90-481-3135-8_9
[18]
Krause, S. (2008) Stromal-Epithelial Interactions in the Mammary Gland: Development of a Tissue Morphogenesis Model. Sackler School of Graduate Biomedical Sciences (Tufts University), Medford.
[19]
Masso-Welch, P.A., et al. (2000) A Developmental Atlas of Rat Mammary Gland Histology. Journal of Mammary Gland Biology and Neoplasia, 5, 165-185. https://doi.org/10.1023/A:1026491221687
[20]
Van Keymeulen, A., et al. (2011) Distinct Stem Cells Contribute to Mammary Gland Development and Maintenance. Nature, 479, 189-193. https://doi.org/10.1038/nature10573
[21]
Gudjonsson, T., et al. (2002) Normal and Tumor-Derived Myoepithelial Cells Differ in Their Ability to Interact with Luminal Breast Epithelial Cells for Polarity and Basement Membrane Deposition. Journal of Cell Science, 115, 39-50.
[22]
Monks, J., et al. (2002) Do Inflammatory Cells Participate in Mammary Gland Involution? Journal of Mammary Gland Biology and Neoplasia, 7, 163-176. https://doi.org/10.1023/A:1020351919634
[23]
Macias, H. and Hinck, L. (2012) Mammary Gland Development. Wiley Interdisciplinary Reviews: Developmental Biology, 1, 533-557. https://doi.org/10.1002/wdev.35
[24]
Al-Eid, H. and Arteh, S. (2005) Cancer Incidence Report Saudi Arabia. Kingdom of Saudi Arabia: Ministry of Health, Saudi Cancer Registry, Riyadh, 1-99.
[25]
Al-Eid, H.S. and Arteh, S. (2003) Cancer Incidence Report Saudi Arabia 2003. Kingdom of Saudi Arabia Ministry of Health National Cancer Registry, Riyadh.
[26]
Alotaibi, R.M., et al. (2018) Breast Cancer Mortality in Saudi Arabia: Modelling Observed and Unobserved Factors. PLoS ONE, 13, e0206148. https://doi.org/10.1371/journal.pone.0206148
[27]
Lozano, R., et al. (2012) Global and Regional Mortality from 235 Causes of Death for 20 Age Groups in 1990 and 2010: A Systematic Analysis for the Global Burden of Disease Study 2010. The Lancet, 380, 2095-2128. https://doi.org/10.1016/S0140-6736(12)61728-0
[28]
Mokdad, A.H., et al. (2014) The State of Health in the Arab World, 1990-2010: An Analysis of the Burden of Diseases, Injuries, and Risk Factors. The Lancet, 383, 309-320. https://doi.org/10.1016/S0140-6736(13)62189-3
[29]
Siegel, R.L., Miller, K.D. and Jemal, A. (2020) Cancer Statistics, 2020. CA: A Cancer Journal for Clinicians, 70, 7-30. https://doi.org/10.3322/caac.21590
[30]
Ibrahim, E.M., et al. (2008) The Present and the Future of Breast Cancer Burden in the Kingdom of Saudi Arabia. Medical Oncology, 25, 387-393. https://doi.org/10.1007/s12032-008-9051-5
[31]
Soffritti, M., et al. (2005) Aspartame Induces Lymphomas and Leukaemias in Rats a L’aspartame Induce Linfomi e Leucemie Nei Ratti. European Journal of Cancer, 10, 107-116.
[32]
Soffritti, M., et al. (2006) First Experimental Demonstration of the Multipotential Carcinogenic Effects of Aspartame Administered in the Feed to Sprague-Dawley Rats. Environmental Health Perspectives, 114, 379-385. https://doi.org/10.1289/ehp.8711
[33]
Soffritti, M., et al. (2010) Aspartame Administered in Feed, Beginning Prenatally through Life Span, Induces Cancers of the Liver and Lung in Male Swiss Mice. American Journal of Industrial Medicine, 53, 1197-1206. https://doi.org/10.1002/ajim.20896
[34]
Soffritti, M., et al. (2007) Life-Span Exposure to Low Doses of Aspartame Beginning during Prenatal Life Increases Cancer Effects in Rats. Environmental Health Perspectives, 115, 1293-1297. https://doi.org/10.1289/ehp.10271
[35]
Gallus, S., et al. (2007) Artificial Sweeteners and Cancer Risk in a Network of Case—Control Studies. Annals of Oncology, 18, 40-44. https://doi.org/10.1093/annonc/mdl346
[36]
Byers, S.L., et al. (2012) Mouse Estrous Cycle Identification Tool and Images. PLoS ONE, 7, e35538. https://doi.org/10.1371/journal.pone.0035538
[37]
Plante, I., Stewart, M.K. and Laird, D.W. (2011) Evaluation of Mammary Gland Development and Function in Mouse Models. JoVE (Journal of Visualized Experiments), 53, e2828. https://doi.org/10.3791/2828
[38]
Drury, R. and Wallington, E. (1980) Carelton’s Histology Technique. 5th Edition, Oxford University Press, Oxford, New York, Toronto.
[39]
Modi, S. and Borges, V. (2005) Artificial Sweeteners: Boon or Bane. International Journal of Diabetes in Developing Countries, 5, 1-6. https://doi.org/10.4103/0973-3930.26753
[40]
Butchko, H.H., et al. (2002) Aspartame: Review of Safety. Regulatory Toxicology and Pharmacology, 35, S1-S93.
[41]
Morroni, M., et al. (2004) Reversible Transdifferentiation of Secretory Epithelial Cells into Adipocytes in the Mammary Gland. Proceedings of the National Academy of Sciences, 101, 16801-16806. https://doi.org/10.1073/pnas.0407647101
[42]
Zwick, R.K., et al. (2018) Adipocyte Hypertrophy and Lipid Dynamics Underlie Mammary Gland Remodeling after Lactation. Nature Communications, 9, Article No. 3592. https://doi.org/10.1038/s41467-018-05911-0
[43]
Gill, J. (2000) The Effects of Moderate Alcohol Consumption on Female Hormone Levels and Reproductive Function. Alcohol and Alcoholism, 35, 417-423. https://doi.org/10.1093/alcalc/35.5.417
[44]
Heine, P., et al. (2000) Increased Adipose Tissue in Male and Female Estrogen Receptor-α Knockout Mice. Proceedings of the National Academy of Sciences, 97, 12729-12734. https://doi.org/10.1073/pnas.97.23.12729
[45]
Nagata, C., et al. (2007) Association of Maternal Fat and Alcohol Intake with Maternal and Umbilical Hormone Levels and Birth Weight. Cancer Science, 98, 869-873. https://doi.org/10.1111/j.1349-7006.2007.00464.x
[46]
Al-Qudsi, F.M. and Al-Hasan, M.M. (2019) In Utero Exposure to Commercial Artificial Sweeteners Affects Mice Development and Mammary Gland Structure. Environmental Science and Pollution Research, 26, 5054-5064. https://doi.org/10.1007/s11356-018-3935-5
[47]
Heil, S.H. and Subramanian, M.G. (1998) Alcohol and the Hormonal Control of Lactation. Alcohol Health and Research World, 22, 178.
[48]
Rybinska, I., et al. (2020) Adipocytes in Breast Cancer, the Thick and the Thin. Cells, 9, 560. https://doi.org/10.3390/cells9030560
