Advertisement

In utero exposure to commercial artificial sweeteners affects mice development and mammary gland structure

  • Fatma M. Al-QudsiEmail author
  • Manar M. Al-Hasan
Research Article

Abstract

Commercial artificial sweeteners present in the market are usually made of combination of nutritive and artificial sweeteners such as sorbitol and aspartame. The aim of this research was to study the effect of in utero exposure to commercial artificial sweeteners on the mouse development and on mammary gland in different stages (18-day embryos and 4-week-old mice). Pregnant mice of treated groups were given 50 mg/kg body weight of commercial artificial sweetener. The dose was given on day 1 of pregnancy until 3-week nursing, while the controls were given distilled water. Congenital malformations were seen in treated 18-day fetus and 4-week-old mice, such as a significant decrease in the diameter of the placenta and the weight of the fetuses, while in 4-week-old mice, a significant decrease in the length of the body, limbs, and tail was seen compared to the controls. The result of this study showed that in 18-day fetuses, clusters of mammary gland in the treated mice seemed to be more differentiated than the controls. In 4-week-old mice, the number of mammary gland ducts in the treated group was significantly more than the control group, and the lumen of the ducts in the treated sections seemed to be narrower than the controls, also many regressing terminal end buds (TEBs) were seen in the treated group. A significant increase in the mammary gland area of treated group was seen compared to the controls.

Keywords

Artificial sweeteners Mouse embryo Congenital malformation Mammary gland Terminal end buds Growth retardation 

Notes

Acknowledgments

We would like to thank King Abdul-Aziz City for Science and Technology for the grant given for the completion of this research (Grant No. 336 -35 - أط).

References

  1. Byers SL, Wiles MV, Dunn SL, Taft RA (2012) Mouse estrous cycle identification tool and images. PLoS One 7(4):1–5CrossRefGoogle Scholar
  2. Cardoso FS et al. (2016). Exposure to sorbitol during lactation causes metabolic alterations and genotoxic effects in rat offspring. Toxicology Letters 260:36–45Google Scholar
  3. Codex alimentarius C (2008) Codex General Standard for Food Additives (GSFA) online database. Rome, Italy, Food and Agriculture Organization of the United Nations (http://www.Codexalimentarius.net/gsfaonline/index.html)
  4. Collison KS, Makhoul NJ, Zaidi MZ, Al-Rabiah R, Inglis A, Andres BL, Ubungen R, Shoukri M, Al-Mohanna FA (2012) Interactive effects of neonatal exposure to monosodium glutamate and aspartame on glucose homeostasis. Nutr Metab (Lond) 9(1):58CrossRefGoogle Scholar
  5. Drury AA, and Wallington EA (1980) Carleton’s histological technique, 5th edition, Oxford, UK: Oxford University press.Google Scholar
  6. Duong A, Steinmaus C, McHale CM, Vaughan CP, Zhang L (2011) Reproductive and developmental toxicity of formaldehyde: a systematic review. Mutat Res 728(3):118–138CrossRefGoogle Scholar
  7. Ginestra E, Saravo L, Ciuna I, Sciacca G, Finocchiaro A, Menzo GL (2004) Evaluation and comparison of deoxyribonucleic acid typing methods on human tissue fixed with different fixatives. Int Congr Ser 1261:574–576CrossRefGoogle Scholar
  8. Hassiotou F, Geddes D (2013) Anatomy of the human mammary gland: current status of knowledge. Clin Anat 26:29–48CrossRefGoogle Scholar
  9. Hedrich H (2004) The laboratory mouse, 1st edition. Academic Press. eBook ISBN 9780080542539Google Scholar
  10. Hovey RC, Trott JF, Vonderhaar BK (2002) Establishing a framework for the functional mammary gland: from endocrinology to morphology. J Mammary Gland Biology and Neoplasia 7:17–38CrossRefGoogle Scholar
  11. Howlin J, Mcbryan J, Martin F (2006) Pubertal mammary gland development: insights from mouse models. J Mammary Gland Biology and Neoplasia 11:283–297CrossRefGoogle Scholar
  12. Islam MS, Sakaguchi E (2006) Sorbitol-based osmotic diarrhea: possible causes and mechanism of prevention investigated in rats. World J Gastroenterol: WJG 12(47):7635CrossRefGoogle Scholar
  13. Kim J-Y, Seo J, Coh K-H (2011) Aspartame-fed zebrafish exhibit acute deaths with swimming defects and saccharin-fed zebrafish have elevation of cholesteryl ester transfer protein activity in hypercholesterolemia. Food Chem Toxicol 49(11):2899–2905CrossRefGoogle Scholar
  14. Krause S (2008) Stromal-epithelial interactions in the mammary gland: development of a tissue morphogenesis model. (Doctoral dissertation, Sackler School of Graduate Biomedical Sciences (Tufts University))Google Scholar
  15. Leme LFAG, Azoubel R (2006) Effects of aspartame on the exocrine pancreas of rat fetuses. Int J Morphol 24:679–684CrossRefGoogle Scholar
  16. Magnuson BA, Burdock GA, Doull J, Kroes RM, Marsh GM, Pariza MW, Spencer PS, Waddell WJ, Walker R, Williams GM (2007) Aspartame: a safety evaluation based on current use levels, regulations, and toxicological and epidemiological studies. CRC Crit Rev Toxicol 37(8):629–727CrossRefGoogle Scholar
  17. Martin J, Avery RA (1998) Effects of tail loss on the movement patterns of the lizard, Psammodromus algirus. Functional Ecology 12(5):794–802CrossRefGoogle Scholar
  18. Martins MRI, Azoubel R, Martins MRI, Azoubel R (2007) Effects of aspartame on fetal kidney: a morphometric and stereological study. Int J Morphol 25(4):689–694CrossRefGoogle Scholar
  19. Masso-Welch PA, Darcy KM, Stangle-Castor NC, Margot M (2000) A developmental atlas of rat mammary gland histology. J Mammary Gland Biol Neoplasia 5(2):165–185CrossRefGoogle Scholar
  20. Michno K, Boras-Granic K, Mill P, Hui CC, Hamel PA (2003) Shh expression is required for embryonic hair follicle but not mammary gland development. Dev Biol 264(1):153–165CrossRefGoogle Scholar
  21. Modi SV, Borges VJ (2005) Artificial sweeteners: boon or bane? Int J Diabetes Dev Countries 25:1–6Google Scholar
  22. Mourad IM, Noor NA (2011) Aspartame (a widely used artificial sweetener) and oxidative stress in the rat cerebral cortex. Int J Pharm Biomed Sci 2(1):4–10Google Scholar
  23. Ozen IT, Karav S, 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(1):4–7Google Scholar
  24. Paine IS, Lewis MT (2017) The terminal end bud: the little engine that could. J Mammary Gland Biol Neoplasia 22(2):93–108CrossRefGoogle Scholar
  25. Plante I, Stewart MK, Laird DW (2011) Evaluation of mammary gland development and function in mouse models. J Visualized Exp: Jove (53):e2828.  https://doi.org/10.3791/2828
  26. Portela GS, Azoubel R, Batigălia F (2007) Effects of aspartame on maternal-fetal and placental weights, length of umbilical cord and fetal liver: a kariometric experimental study. Int J Morphol 25(3):549–554CrossRefGoogle Scholar
  27. Puică C, Crăcium C, Rusu M, Cristescu M, Borsa M & Roman I (2008) Ultrastructural aspects concerning the hypothalamus-pituitary complex reactivity following chronic administration of aspartame in juvenile rabbits. Bulletin UASVM, Veterinary Medicine 65(1)/ pISSN 1843–5270; eISSN 1843–5378Google Scholar
  28. Puică C, Crăcium C, Rusu M, Cristescu M, Borsa M, & Roman I (2009). Ultrastructural aspects concerning the hypothalamus-pituitary complex reactivity following chronic administration of aspartame in juvenile rats. Studia Universitatis “Vasile Goldiş”, Seria Ştiinţele Vieţii 19:19–24Google Scholar
  29. Richert MM, Schwertfeger KL, Ryder JW, Anderson SM (2000) An atlas of mouse mammary gland development. J Mammary Gland Biol Neoplasia 5(2):227–241CrossRefGoogle Scholar
  30. Silberstein GB (2001) Postnatal mammary gland morphogenesis. Microsc Res Tech 52(2):155–162CrossRefGoogle Scholar
  31. Siripurkpong P, Fungkrajai M, Kongkhum S, & Piumngam K (2014) Sorbitol has no significant effects on 3T3-L1 -adipogenesis and adiponectin synthesis and secretion. Thammasat Int J Sci Technol 19(2)Google Scholar
  32. Soffritti M, Belpoggi F, Degli Esposti D, Lambertini L (2005) Aspartame induces lymphomas and leukaemias in rats L’aspartame induce linfomi e leucemie nei ratti. Eur J Oncol 10(2):107–116Google Scholar
  33. Soffritti M, Belpoggi F, Degli Esposti D, Lambertini L, Tibaldi E, Rigano A (2006) First experimental demonstration of the multipotential carcinogenic effects of aspartame administered in the feed to Sprague-Dawley rats. Environ Health Perspect 114(3):379–385CrossRefGoogle Scholar
  34. Soffritti M, Belpoggi F, Tibaldi E, Degli ED, Lauriola M (2007) Life-span exposure to low doses of aspartame beginning during prenatal life increases Cancer effects in rats. Environ Health Perspect 115(9):1293–1297CrossRefGoogle Scholar
  35. Soffritti M, Belpoggi F, Manservigi M, Tibaldi E, Lauriola M, Falcioni L, Bua L (2010) Aspartame administered in feed, beginning prenatally through life span, induces cancers of the liver and lung in male Swiss mice. Am J Ind Med 53(12):1197–1206CrossRefGoogle Scholar
  36. Sordillo LM, Shafer-Weaver K, Derosa D (1997) Immunobiology of the mammary gland. Dairy Science 80(8):1851–1865CrossRefGoogle Scholar
  37. Stegink LD and Filer LG (1984) Aspartame: physiology and biochemistry. 1st edition (Vol. 12). Series food science and technology. CRC PressGoogle Scholar
  38. Veltmaat JM, Mailleux AA, Thiery JP, Bellusci S (2003) Mouse embryonic mammogenesis as a model for the molecular regulation of pattern formation. Differentiation 71(1):1–17CrossRefGoogle Scholar
  39. Vorbach C, Capecchi MR, Penninger JM (2006) Evolution of the mammary gland from the innate immune system? Bioessays 28(6):606–616CrossRefGoogle Scholar
  40. Washburn C, & Christensen N (2012) Sugar substitutes: artificial sweeteners and sugar alcoholsGoogle Scholar
  41. Watson CJ (2006) Involution: apoptosis and tissue remodelling that convert the mammary gland from milk factory to a quiescent organ. Breast Cancer Res 8(2):203CrossRefGoogle Scholar
  42. Walker C, Vierck CJ, Ritz LA (1998) Balance in the cat: role of the tail and effects of sacrocaudal transection. Behav Brain Res 91(1):41–47CrossRefGoogle Scholar
  43. Zaidi Z & Lanigan SW (2010) Dermatology in clinical practice. Springer Verlag London . eBook ISBN 978-1-84882-862-9Google Scholar

Copyright information

© Springer-Verlag GmbH Germany, part of Springer Nature 2019

Authors and Affiliations

  1. 1.Biology DepartmentKing abdulaziz UniversityJeddahSaudi Arabia

Personalised recommendations