1110-0559 © 2012 The Egyptian Journal of Histology DOI: 10.1097/01.EHX.0000410867.09671.2f 43 Introduction Diabetes is relatively common worldwide. According to the reports of the WHO, more than 150 million people suffer from diabetes across the world [1]. A primary negative effect of a diabetic environment on the developing embryo is impaired vascularization of the yolk sac and, consequently, impaired delivery of nutrition to the embryo, which leads to developmental damage in the growing embryo [2]. Two endometrial vascular events characterize the early stages of embryo implantation in rats. The first is a localized increase in endometrial vascular permeability, leading to tissue edema. The second is increased cell proliferation. Endothelial cell proliferation increased at embryo sites only from day 6 and decreased to basal values at intersites, which are defined as the areas between implantation sites [3]. Significant angiogenesis at the sites of blastocyst implantation was associated with increased vascular permeability. In rats, increased uterine vascular permeability occurs on the afternoon of day 5 of gestation and lasts for a short period, known as the receptive phase [4]. In the human endometrium, vascular endothelial growth factor (VEGF) was detected in the mRNA throughout the menstrual cycle with maximal expression during the secretory phase. This protein was predominantly localized in glandular epithelial cells, suggesting that VEGF might play a central role during embryo implantation [5]. The aim of the work was to study the effect of diabetes on the implantation site and intersite in albino rats during the early period of pregnancy, with special emphasis on angiogenesis, by studying VEGF expression. Department of Anatomy and Embryology, Faculty of Medicine, Ain Shams University, Cairo, Egypt Correspondence to Youssef Shoukry, Department of Anatomy and Embryology, Faculty of Medicine, Ain Shams University, Cairo, Egypt Tel: + 20 1001690550; fax: +00226837673; e-mail: dr_yosef@hotmail.com Received 26 July 2011 Accepted 17 September 2011 The Egyptian Journal of Histology 2012, 35:43-53 6 (1323-2012) Background Diabetes is relatively common worldwide. According to the reports of the WHO, more than 150 million people suffer from diabetes across the world. A primary negative effect of a diabetic environment on the developing embryo is impaired vascularization of the yolk sac. Angiogenesis at the sites of blastocyst implantation is associated with increased vascular permeability. Aim The present study aimed to investigate the effect of diabetes on the implantation site and intersite in albino rats during the early period of pregnancy, with special emphasis on angiogenesis, by studying vascular endothelial growth factor expression. Materials and method Forty adult female albino rats aged 4–6 months were used in this study. Rats were divided into two groups (20 rats each). Group I constituted the control group and group II constituted the alloxan-induced diabetic group. Diabetes was induced in rats by intravenous injection of alloxan monohydrate dissolved in normal saline into the dorsal tail vein at a dose of 40 mg/kg body weight. Vaginal smears were collected from each animal; the presence of sperm in the smear was designated as day 1 of pregnancy. Pregnant rats from the control and diabetic groups were sacrifced at days 4, 5, 6, and 7 of pregnancy (n=5). Examination of the uterine horn sections showed occurrence of implantation on day 6 in the control group, whereas implantation in the diabetic group occurred only on day 7. Granulated metrial glandular cells were clearly seen in the control group, whereas lymphocytic infltration was obvious in the diabetic group. The expression of vascular endothelial growth factor was stronger in the diabetic group. Keywords: alloxan, angiogenesis, diabetes, implantation, pregnant rats Egypt J Histol 35:43-53 © 2012 The Egyptian Journal of Histology 1110-0559 Effect of alloxan-induced diabetes on implantation sites of pregnant rats with special emphasis on angiogenesis Fatma Ibrahim Khalil Elrakhawy, Rania A. Salah El Din, Youssef Shoukry and Amgad Gaber Alsaid Salem Original article Copyright © The Egyptian Journal of Histology. Unauthorized reproduction of this article is prohibited.