Histopathological, Ultrastructural and Apoptotic Changes in Diabetic Rat Placenta

Yıl 2015, Cilt: 32 Sayı: 3, 296 - 302, 01.07.2015

Mehmet Gül Nuray Bayat Aslı Çetin Remziye Aysun Kepekçi Yavuz Şimşek Başak Kayhan Uğur Turhan Ali Otlu

Öz

Background: The exchange of substances between mother and fetus via the placenta plays a vital role during development. A number of developmental disorders in the fetus and placenta are observed during diabetic pregnancies. Diabetes, together with placental apoptosis, can lead to developmental and functional disorders. Aims: Histological, ultrastructural and apoptotic changes were investigated in the placenta of streptozotocin (STZ) induced diabetic rats. Study Design: Animal experimentation. Methods: In this study, a total of 12 female Wistar Albino rats (control (n=6) and diabetic (n=6)) were used. Rats in the diabetic group, following the administration of a single dose of STZ, showed blood glucose levels higher than 200 mg/dL after 72 hours. When pregnancy was detected after the rats were bred, two pieces of placenta and the fetuses were collected on the 20th day of pregnancy by cesarean incision under ketamine/xylazine anesthesia from in four rats from the control and diabetic groups. Placenta tissues were processed for light microscopy and transmission electron microscopy (TEM). Hematoxylin-eosin (HE) and periodic acid Schiff-diastase (PAS-D) staining for light microscopic and caspase-3 staining for immunohistochemical investigations were performed for each placenta. Electron microscopy was performed on thin sections contrasted with uranyl acetate and lead nitrate. Results: Weight gain in the placenta and fetuses of diabetic rats and thinning of the decidual layer, thickening of the hemal membrane, apoptotic bodies, congestion in intervillous spaces, increased PAS-D staining in decidual cells and caspase-3 immunoreactivity were observed in the diabetic group. After the ultrastructural examination, the apoptotic appearance of the nuclei of trophoblastic cells, edema and intracytoplasmic vacuolization, glycogen accumulation, dilation of the endoplasmic reticulum and myelin figures were observed. In addition, capillary basement membrane thickening, capillary endothelial cells chromatin condensation in the nucleus and corrugation of the nucleus were found. Conclusion: Diabetes causes histomorphometric, ultrastructural and apoptotic changes in rat placenta.

Anahtar Kelimeler

Apoptosis, diabetes, histopathology, placenta, ultrastructure

Kaynakça

• 1. Gewolb I, Merdian W, Warshaw J, Enders A. Fine structural abnormalities of the placenta in diabetic rats. Diabetes 1986;35:1254-61. [CrossRef]
• 2. Higgins M, Felle P, Mooney E, Bannigan J, McAuliffe F. Stereology of the placenta in type 1 and type 2 diabetes. Placenta 2011;32:564-9. [CrossRef]
• 3. Mathiesen ER, Ringholm L, Damm P. Stillbirth in diabetic pregnancies. Best Pract Res Clin Obstet Gynaecol 2011;25:105-11. [CrossRef]
• 4. Greene DA, Stevens MJ, Obrosova I, Feldman EL. Glucoseinduced oxidative stress and programmed cell death in diabetic neuropathy. Eur J Pharmacol 1999;375:217-23. [CrossRef]
• 5. Vambergue A, Fajardy I. Consequences of gestational and pregestational diabetes on placental function and birth weight. World J Diabetes 2011;2:196-203.
• 6. Sinzato YK, Volpato GT, Iessi IL, Bueno A, Calderon IdMP, Rudge MVC, et al. Neonatally Induced Mild Diabetes in Rats and Its Effect on Maternal, Placental, and Fetal Parameters. Exp Diabetes Res 2012;2012:108163. [CrossRef]
• 7. Sharp AN, Heazell AE, Crocker IP, Mor G. Placental apoptosis in health and disease. Am J Reprod Immunol 2010;64:159-69. [CrossRef]
• 8. Ferrer I, Planas AM. Signaling of cell death and cell survival following focal cerebral ischemia: life and death struggle in the penumbra. J Neuropathol Exp Neurol 2003;62:329-39.
• 9. Porter AG, Jänicke RU. Emerging roles of caspase-3 in apoptosis. Cell Death Differ 1999;6:99-104. [CrossRef]
• 10. Honda M, Toyoda C, Nakabayashi M, Omori Y. Quantitative investigations of placental terminal villi in maternal diabetes mellitus by scanning and transmission electron microscopy. Tohoku J Exp Med 1992;167:247-57. [CrossRef]
• 11. Gluckman PD, Harding JE. Nutritional and hormonal regulation of foetal growth-involving concepts. Acta Paediatr Suppl 1994;399:60-3. [CrossRef]
• 12. Toledo M. T, Ventrucci G, Marcondes M. C. Cancer during pregnancy alters the activity of rat placenta and enhances the expression of cleaved PARP, cytochrome-c and caspase 3. BMC Cancer 2006;6:168. [CrossRef]
• 13. Aplin J. Maternal influences on placental development. Sem Cell Dev Biol 2000;115-25.
• 14. Brosens J, Gellersen B. Death or survival-progesterone-dependent cell fate decisions in the human endometrial stroma. J Mol Endocrinol 2006;36:389-98. [CrossRef]
• 15. Chang AS, Dale AN, Moley KH. Maternal diabetes adversely affects preovulatory oocyte maturation, development, and granulosa cell apoptosis. Endocrinology 2005;146:2445-53. [CrossRef]
• 16. Gheorman L, Pleşea I, Gheorman V. Histopathological considerations of placenta in pregnancy with diabetes. Rom J Morphol Embryol 2012;53:329-36.
• 17. Schaffer SW, Mozaffari MS. The neonatal STZ model of diabetes. In: McNeill JH, editor. Experimental models of dia- betes. Boca Raton, FL: CRC Press, 1999:231-55.
• 18. Soulimane-Mokhtari NA, Guermouche B, Yessoufou A, Saker M, Moutairou K, Hichami A, et al. Modulation of lipid metabolism by n-3 polyunsaturated fatty acids in gestational diabetic rats and their macrosomic offspring. Clin Sci (Lond) 2005;109:287-95. [CrossRef]
• 19. Benirschke K, Kaufmann P, Baergen RN. 6th ed. Berlin-Germany: Pathology of the human placenta; 2006.
• 20. Barash V, Gutman A., Shafrir E. Fetal diabetes in rats and its effect on placental glycogen. Diabetologia 1985;28:244-9. [CrossRef]
• 21. Pietryga M, Biczysko W, Wender-Ozegowska E, Brazert J, Biegańska E, Biczysko R. Ultrastructural examination of the placenta in pregnancy complicated by diabetes mellitus. Ginekol Pol 2004;75:111-8.
• 22. Jones C, Fox H. Placental changes in gestational diabetes: an ultrastructural study. Obstet Gynecol 1976;48:274-80.
• 23. Damasceno DC, Volpato GT, Paranhos C, I. D. M., Cunha R. Oxidative stress and diabetes in pregnant rats. Anim Reprod Sci 2002;72:235-44. [CrossRef]
• 24. Kannan K, Jain SK. Oxidative stress and apoptosis. Pathophysiaology 2000;7:153-63. [CrossRef]
• 25. Majno G, Joris I. Cells, Tissues, and Disease: Principles of General Pathology: Oxford University Press, USA 2004; 1005.
• 26. Giacco F, Brownlee M. Oxidative stress and diabetic complications. Circ Res 2010;107:1058-70. [CrossRef]
• 27. Reece EA, Ma XD, Zhao Z, Wu YK, Dhanasekaran D. Aberrant patterns of cellular communication in diabetes-induced embryopathy in rats: II, apoptotic pathways. Am J Obstet Gynecol 2005;192:967-72. [CrossRef]
• 28. Ho FM, Liu SH, Liau, CS, Huang PJ, Lin-Shiau SY. High glucose-induced apoptosis in human endothelial cells is mediated by sequential activations of c-Jun NH(2)-terminal kinase and caspase-3. Circulation 2000;101:2618-24. [CrossRef]