Severity of prepregnancy diabetes on the fetal malformations and viability associated with early embryos in rats

Author(s)

Bueno, Aline ^[1] ; Sinzato, Yuri Karen ^[1] ; Volpato, Gustavo Tadeu ^[2] ; Gallego, Franciane Quintanilha ^[1] ; Perecin, Felipe ^[3] ; Rodrigues, Tiago ^[4] ; Damasceno, Debora Cristina ^[1]

Affiliation

^[1] Sao Paulo State Univ Unesp, Botucatu Med Sch, Lab Expt Res Gynecol & Obstet, Postgrad Course Tocogynecol, Botucatu, SP - Brazil

^[2] Fed Univ Mato Grosso UFMT, Inst Biol & Hlth Sci, Lab Syst Physiol & Reprod Toxicol, Barra Do Garcas, MG - Brazil

^[3] Univ Sao Paulo, Fac Anim Sci & Food Engn, Dept Vet Med, Pirassununga, SP - Brazil

^[4] Fed Univ ABC UFABC, Ctr Nat & Human Sci CCNH, Santo Andre, SP - Brazil

• Document type: Journal article
• Source: BIOLOGY OF REPRODUCTION; v. 103, n. 5, p. 938-950, NOV 2020.
• Web of Science Citations: 0

Abstract

Preexisting/pregestational diabetes enhances the risk of birth defects. Several factors have been involved during the implantation process, such as cytokines (granulocyte-macrophage-colonystimulating factor {[}GM-CSF]). The objective was to evaluate the effects of two levels of diabetes on the redox status of preimplantation embryos during the implantation process to comprehend how both are involved in embryo and fetal viability against maternal diabetes. Female Sprague-Dawley rats received streptozotocin at birth (mild diabetes {[}MD]) or at adulthood (severe diabetes {[}SD]) to obtain two experimental diabetes intensities. After confirming the diabetic status, the nondiabetic and diabetic groups were mated around day 110 of life. At gestational day (GD) 21, fetuses were assessed for viability and malformations and ovaries for embryo loss before implantation. Other pregnant nondiabetic and diabetic rats were sacrificed at GD2-4 for maternal and preimplantation embryo oxidative stress markers, maternal serum insulin, uterine fluid GM-CSF, and preimplantation embryo morphological analysis. MD and SD caused abnormal redox levels, lower GM-CSF and insulin levels during the preimplantation period, and embryonic loss before implantation. SD caused lower fetal viability and higher fetal malformation percentages at GD21. The SD dam-derived preimplantation embryos presented lower glutathione levels and higher thiobarbituric acid reactive substances concentration at GD3 and an increased frequency of abnormal preimplantation embryos at GD4. In conclusion, preexisting diabetes leads to complications in the implantation process. Furthermore, maternal oxidative stress and other metabolic changes alter the redox state and morphological structure of preimplantation embryos, contributing to damaged growth and development in late pregnancy. {[}GRAPHICS] . (AU)

• FAPESP's process: 12/17275-0 - Antioxidant system role and gender influence on the in vivo developmental competence of early embryos in different models of experimental diabetes
• Grantee: Débora Cristina Damasceno
• Support Opportunities: Regular Research Grants
• FAPESP's process: 19/06735-9 - Regulation of fuel metabolism associated with pluripotency and differentiation by the diabetes-regulated embryonic gene, Pax3
• Grantee: Débora Cristina Damasceno
• Support Opportunities: Scholarships abroad - Research
• FAPESP's process: 11/23721-0 - Antioxidant system role and gender influences on the in vivo developmental competence of embryos at different models of experimental diabetes
• Grantee: Aline Bueno
• Support Opportunities: Scholarships in Brazil - Doctorate
• FAPESP's process: 13/16548-5 - Study of epigenetic regulation of the embryonic gene, PAX3, by diabetic pregnancy-induced oxidative stress
• Grantee: Aline Bueno
• Support Opportunities: Scholarships abroad - Research Internship - Doctorate