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Heat shock protein production and immunity and altered fetal development in diabetic pregnant rats
Authors:Felipe Hiroshi Saito  Débora Cristina Damasceno  Bruna Dallaqua  Iara Moreno Linhares  Marilza Vieira Cunha Rudge  Iracema De Mattos Paranhos Calderon  Steven S. Witkin
Affiliation:1. Laboratory of Experimental Research on Gynecology and Obstetrics, Department of Gynecology and Obstetrics, UNESP—Universidade Estadual Paulista, Botucatu Medical School, Sao Paulo, Brazil
2. Department of Gynecology, University of Sao Paulo Medical School and Hospital das Clínicas, Sao Paulo, Brazil
3. Division of Immunology and Infectious Diseases, Department of Obstetrics and Gynecology, Weill Cornell Medical College, New York, NY, USA
4. Department of Obstetrics and Gynecology, Weill Cornell Medical College, 525 East 68th Street, Box 35, New York, NY, 10065, USA
Abstract:We evaluated associations between the concentrations of heat shock proteins (hsp60 and hsp70) and their respective antibodies, alterations in maternal reproductive performance, and fetal malformations in pregnant rats with hyperglycemia. Mild diabetes (MD) or severe diabetes (SD) was induced in Sprague-Dawley rats prior to mating; non-treated non-diabetic rats (ND) served as controls. On day 21 of pregnancy, maternal blood was analyzed for hsp60 and hsp70 and their antibodies; and fetuses were weighed and analyzed for congenital malformations. Hsp and anti-hsp levels were correlated with blood glucose levels during gestation. There was a positive correlation between hsp60 and hsp70 levels and the total number of malformations (R = 0.5908, P = 0.0024; R = 0.4877, P = 0.0134, respectively) and the number of malformations per fetus (R = 0.6103, P = 0.0015; R = 0.4875, P = 0.0134, respectively). The anti-hsp60 IgG concentration was correlated with the number of malformations per fetus (R = 0.3887, P = 0.0451) and the anti-hsp70 IgG level correlated with the total number of malformations (R = 0.3999, P = 0.0387). Moreover, both hsp and anti-hsp antibodies showed negative correlations with fetal weight. The results suggest that there is a relationship between hsp60 and hsp70 levels and their respective antibodies and alterations in maternal reproductive performance and impaired fetal development and growth in pregnancies associated with diabetes.
Keywords:Diabetes   Pregnancy   Malformation   Heat shock protein
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