Effect of mild gestational diabetes mellitus on histological, ultrastructural, and quantitative morphometric alterations of rat fetal liver

Document Type : Original Article

Authors

1 Golestan Research Center of Gastroenterology and Hepatology, Golestan University of Medical Sciences, Gorgan, Iran

2 Gorgan Congenital Malformations Research Center, Golestan University of Medical Sciences, Gorgan, Iran

3 Pathology Department of Shahid Kamyab Hospital, Mashhad University of Medical Sciences, Mashhad, Iran

4 Medical Cellular and Molecular Research Centre, Golestan University of Medical Sciences, Gorgan, Iran

5 Environmental Health Research Center, Department of Biostatistics and Epidemiology, Faculty of Health, Golestan University of Medical Sciences, Gorgan, Iran

10.22038/ijbms.2024.78920.17069

Abstract

Objective(s): Gestational diabetes mellitus (GDM), one of the most common metabolic disorders in pregnancy, impacts maternal and fetal health. This study was designed to assess the effects of mild GDM on the histology, ultrastructure, and morphometry of fetal liver tissue.
Materials and Methods: In this experimental study, twenty pregnant rats were randomly allocated into control and streptozotocin (STZ)-induced diabetic groups. Mild hyperglycemia was induced by intraperitoneal injection of STZ (40 mg/kg/bw) on the 5th day of gestation. At day 19 of gestation, fetal livers were separated and subjected to histological, transmission electron microscopic, and quantitative morphometric examinations.
Results: In the GDM group, PAS staining was positive, revealing scattered eosinophilic inclusions in some hepatocytes. Masson trichrome staining was also positive and showed some fibrous tissue as fine fibers in the portal spaces that extended to the central vein. Reticulin staining in the GDM group was focally positive in the areas of fibrosis and the portal spaces. Ultrastructural examination showed pyknotic nuclei, karyolysis, degranulation and vesiculation of the rough endoplasmic reticulum, and degeneration of mitochondria in the GDM group. The morphometric examination demonstrated that the mean area of hepatocytes was significantly lower in the GDM group than in the control group (P<0.05). Moreover, the mean diameter of the central vein and the density of megakaryocytes were significantly higher in the GDM group than in the control group (P<0.05). 
Conclusion: Uncontrolled mild GDM induced the histological, ultrastructural and morphometric alterations in the fetal liver.

Keywords

Main Subjects


1. World Health Organization (WHO). The top 10 causes of death. https://www.who.int/news-room/fact-sheets/detail/the-top-10-causes-of-death.
2. Carr DB, Gabbe S. Gestational diabetes: Detection, management, and implications. Clinical Diabetes 1998; 16: 4-12.
3. Group HSCR, Metzger BE, Lowe LP, Dyer AR, Trimble ER, Chaovarindr U, et al. Hyperglycemia and adverse pregnancy outcomes. N Engl J Med 2008; 358: 1991-2002.
4. Perkins JM, Dunn JP, Jagasia SM. Perspectives in gestational diabetes mellitus: A review of screening, diagnosis, and treatment. Clinical Diabetes 2007; 25: 57-62.
5. Pedersen J. Weight and length at birth of infants of diabetic mothers. Eur J Endocrinol 1954; 16: 330-342.
6. Langer O. Fetal macrosomia: etiologic factors. Clin Obstet Gynecol 2000; 43: 283-297.
7. Larciprete G, Valensise H, Vasapollo B, Novelli GP, Parretti E, Altomare F, et al. Fetal subcutaneous tissue thickness (SCTT) in healthy and gestational diabetic pregnancies. Ultrasound Obstet Gynecol 2003; 22: 591-597.
8. Khoury JC, Dolan LM, VanDyke R, Rosenn B, Feghali M, Miodovnik M. Fetal development in women with diabetes: imprinting for a life-time? J Matern Fetal Neonatal Med 2012; 25: 11-14.
9. Gojnic M, Stefanovic T, Perovic M, Arsic B, Garalejic E, Micic J, et al. Prediction of fetal macrosomia with ultrasound parameters and maternal glycemic controls in gestational diabetes mellitus. Clin Exp Obstet Gynecol 2012; 39: 512-515.
10. Canavan JP, Holt J, Goldspink DF. Growth of the rat foetal liver in gestational diabetes. Comp Biochem Physiol A Physiol 1991; 99: 473-476.
11. Nazari Z, Nabiuni M, Saeidi M, Golalipour MJ. Gestational diabetes leads to down-regulation of CDK4-pRB-E2F1 pathway genes in pancreatic islets of rat offspring. Iran J Basic Med Sci 2017; 20: 150-154.
12. Cederberg J, Picard JJ, Eriksson UJ. Maternal diabetes in the rat impairs the formation of neural-crest derived cranial nerve ganglia in the offspring. Diabetologia 2003; 46: 1245-1251.
13. Merzouk H, Madani S, Chabane Sari D, Prost J, Bouchenak M, Belleville J. Time course of changes in serum glucose, insulin, lipids and tissue lipase activities in macrosomic offspring of rats with streptozotocin-induced diabetes. Clin Sci (Lond) 2000; 98: 21-30.
14. Damasceno DC, Sinzato YK, Bueno A, Netto AO, Dallaqua B, Gallego FQ, et al. Mild diabetes models and their maternal-fetal repercussions. J Diabetes Res 2013; 2013: 473575.
15. Saito FH, Damasceno DC, Kempinas WG, Morceli G, Sinzato YK, Taylor KN, et al. Repercussions of mild diabetes on pregnancy in Wistar rats and on the fetal development. Diabetol Metab Syndr 2010; 2:26.
16. Bozzala JJ, Russel LD. Electron Microscopy Principles Techniques for Biologists, Jones and Barlett Publishers, Sudbury, Massachusetts. 2 nd Edition. 1998, 19-45, 72-144.
17. El-Sayyad HIH, Al-Haggar MMS, El-Ghawet HA, Bakr IHM. Effect of maternal diabetes and hypercholesterolemia on fetal liver of albino Wistar rats. Nutrition 2014; 30: 326-336.
18. Alshathly MR. Efficacy of Ginger (Zingiber officinale) in ameliorating streptozotocin-induced diabetic liver injury in rats: Histological and biochemical studies. J Microsc Ultrastruct 2019; 7: 91-101.
19. Salahshoor MR, Mohammadi MM, Roshankhah S, Najari N, Jalili C. Effect of Falcaria vulgaris on oxidative damage of liver in diabetic rats. J Diabetes Metab Disord 2019;18:15-23.
20. Golalipour MJ, Ghafari S, Farsi MM. Effect of Urtica dioica L. Extract on quantitative morphometric alterations of liver parenchymal cells in STZ diabetic rats. Int J Morphol 2009; 27: 1339-1344.
21. Roshankhah S, Shabanizadeh A, Abdolmaleki A, Gholami MR, Salahshoor MR. Evaluation of biomarkers in liver following Solanum melongena green calyx administration in diabetic rats. J Diabetes Metab Disord 2020; 19: 1115-1127.
22. Welt K, Weiss J, Martin R, Dettmer D, Hermsdorf T, Asayama K, et al. Ultrastructural, immunohistochemical and biochemical investigations of the rat liver exposed to experimental diabetes und acute hypoxia with and without application of Ginkgo extract. Exp Toxicol Pathol 2004; 55: 331-345.
23. Mohamed S, Salem N, Hassan H, Abdelrahman G. Role of vitamin E in modulating the effect of Streptozotocin-induced maternal diabetes on fetal liver development in albino rat. Medicine Updates 2021; 7: 25-47.
24. Mahata LE, Ali H, Murni AW. Effect of streptozotocin on liver histology damage in rats model of gestational diabetes mellitus. Int J Res Rev 2021; 8: 18-22.
25. Ugwu MN, Umar IA, Utu-Baku AB, Dasofunjo K, Ukpanukpong RU, Yakubu OE, et al. Anti-oxidant status and organ function in streptozotocin-induced diabetic rats treated with aqueous, methanolic and petroleum ether extracts of Ocimum basilicum leaf. J Appl Pharm Sci 2013; 3: S75- S79.