Franciane Quintanilha Gallego1, Yuri Karen Sinzato1, Carolina Abreu Miranda1, Isabela Lovizutto Iessi1, Bruna Dallaqua2, Gustavo Tadeu Volpato3, Wellerson Rodrigo Scarano4, Sebastian SanMartín5, Débora Cristina Damasceno6. 1. Laboratory of Experimental Research on Gynecology and Obstetrics, Gynecology, Obstetrics and Mastology Post Graduate Course, Botucatu Medical School, Univ Estadual Paulista_Unesp, Botucatu, São Paulo State, Brazil. 2. DeVry Ruy Barbosa School (DeVry Brazil Group), Salvador, Bahia State, Brazil. 3. Laboratory of System Physiology and Reproductive Toxicology, Institute of Biological and Health Sciences, Federal University of Mato Grosso (UFMT), Barra do Garças, Mato Grosso State, Brazil. 4. Department of Morphology, Botucatu Bioscience Institute, Univ Estadual Paulista_Unesp, Botucatu, São Paulo State, Brazil. 5. Biomedical Research Centre, Universidad de Valparaíso, Valparaíso, Chile. 6. Laboratory of Experimental Research on Gynecology and Obstetrics, Gynecology, Obstetrics and Mastology Post Graduate Course, Botucatu Medical School, Univ Estadual Paulista_Unesp, Botucatu, São Paulo State, Brazil. Electronic address: debora.damasceno@unesp.br.
Abstract
AIMS: The objective of this study was to assess the mechanisms underlying pancreatic islet adaptation in diabetic mothers and their pups. Additionally, the influence of pancreatic adaptations on maternal reproductive performance was also investigated. MAIN METHODS: Wistar rats were injected with streptozotocin for diabetes induction. At adulthood (3 months), all animals underwent an oral glucose tolerance test (OGTT) for glucose assessment as an inclusion criterion. Following, the animals were mated. At day 18 of pregnancy, the mothers were killed for blood collect ion to determine fasting insulin and glucagon concentrations. The pancreas was removed and processed for the immunohistochemical analysis of insulin, glucagon, somatostatin, Ki-67 and PDX-1, superoxide dismutase 1 (SOD-1), glutathione peroxidase (GSH-Px) and malondialdehyde (MDA). The pregnant uterus was also collected for the evaluation of embryofetal loss. KEY FINDINGS: The diabetic rats showed increased glucose, serum glucagon and insulin concentrations, and embryofetal loss rates. They also showed a reduction in pancreatic islets area and percentage of cells stained for insulin, increased the percentage of non-β cells (alpha e delta cells) stained for Ki-67, glucagon, and somatostatin. Moreover, the cells stained for somatostatin were spread across the islets and showed stronger staining for MDA and weaker staining for GSH-Px. SIGNIFICANCE: Diabetes leads to adaptive responses from the endocrine pancreas in pregnancy that especially involves non-β cells, modifying the mantle-core structure. Nonetheless, these adaptations are not enough for glucose homeostasis and affect the maternal environment, which in turn impairs fetal development.
AIMS: The objective of this study was to assess the mechanisms underlying pancreatic islet adaptation in diabetic mothers and their pups. Additionally, the influence of pancreatic adaptations on maternal reproductive performance was also investigated. MAIN METHODS:Wistar rats were injected with streptozotocin for diabetes induction. At adulthood (3 months), all animals underwent an oral glucose tolerance test (OGTT) for glucose assessment as an inclusion criterion. Following, the animals were mated. At day 18 of pregnancy, the mothers were killed for blood collect ion to determine fasting insulin and glucagon concentrations. The pancreas was removed and processed for the immunohistochemical analysis of insulin, glucagon, somatostatin, Ki-67 and PDX-1, superoxide dismutase 1 (SOD-1), glutathione peroxidase (GSH-Px) and malondialdehyde (MDA). The pregnant uterus was also collected for the evaluation of embryofetal loss. KEY FINDINGS: The diabeticrats showed increased glucose, serum glucagon and insulin concentrations, and embryofetal loss rates. They also showed a reduction in pancreatic islets area and percentage of cells stained for insulin, increased the percentage of non-β cells (alpha e delta cells) stained for Ki-67, glucagon, and somatostatin. Moreover, the cells stained for somatostatin were spread across the islets and showed stronger staining for MDA and weaker staining for GSH-Px. SIGNIFICANCE: Diabetes leads to adaptive responses from the endocrine pancreas in pregnancy that especially involves non-β cells, modifying the mantle-core structure. Nonetheless, these adaptations are not enough for glucose homeostasis and affect the maternal environment, which in turn impairs fetal development.
Authors: Nathália C D Macedo; Isabela L Iessi; Franciane Q Gallego; Aline O Netto; Yuri K Sinzato; Gustavo T Volpato; Elena Zambrano; Débora C Damasceno Journal: Reprod Sci Date: 2021-01-29 Impact factor: 3.060
Authors: Giovana Vesentini; Angélica M P Barbosa; Débora C Damasceno; Gabriela Marini; Fernanda Piculo; Selma M M Matheus; Raghavendra L S Hallur; Sthefanie K Nunes; Bruna B Catinelli; Claudia G Magalhães; Roberto Costa; Joelcio F Abbade; José E Corrente; Iracema M P Calderon; Marilza V C Rudge Journal: PLoS One Date: 2020-04-03 Impact factor: 3.240