PMID- 32870261 OWN - NLM STAT- MEDLINE DCOM- 20211018 LR - 20211018 IS - 1529-7268 (Electronic) IS - 0006-3363 (Linking) VI - 103 IP - 5 DP - 2020 Oct 29 TI - Severity of prepregnancy diabetes on the fetal malformations and viability associated with early embryos in ratsdagger. PG - 938-950 LID - 10.1093/biolre/ioaa151 [doi] AB - Preexisting/pregestational diabetes enhances the risk of birth defects. Several factors have been involved during the implantation process, such as cytokines (granulocyte-macrophage-colony-stimulating 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. CI - (c) The Author(s) 2020. Published by Oxford University Press on behalf of Society for the Study of Reproduction. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com. FAU - Bueno, Aline AU - Bueno A AD - Laboratory of Experimental Research on Gynecology and Obstetrics, Postgraduate Course on Tocogynecology, Botucatu Medical School, Sao Paulo State University (Unesp), Botucatu, Sao Paulo State, Brazil. FAU - Sinzato, Yuri Karen AU - Sinzato YK AD - Laboratory of Experimental Research on Gynecology and Obstetrics, Postgraduate Course on Tocogynecology, Botucatu Medical School, Sao Paulo State University (Unesp), Botucatu, Sao Paulo State, Brazil. FAU - Volpato, Gustavo Tadeu AU - Volpato GT AD - Laboratory of System Physiology and Reproductive Toxicology, Institute of Biological and Health Sciences, Federal University of Mato Grosso (UFMT), Barra do Garcas, Mato Grosso State, Brazil. FAU - Gallego, Franciane Quintanilha AU - Gallego FQ AD - Laboratory of Experimental Research on Gynecology and Obstetrics, Postgraduate Course on Tocogynecology, Botucatu Medical School, Sao Paulo State University (Unesp), Botucatu, Sao Paulo State, Brazil. FAU - Perecin, Felipe AU - Perecin F AD - Faculty of Animal Science and Food Engineering, Department of Veterinary Medicine, University of Sao Paulo (USP), Pirassununga, Sao Paulo State, Brazil. FAU - Rodrigues, Tiago AU - Rodrigues T AD - Center of Natural and Human Sciences (CCNH), Federal University of ABC (UFABC), Santo Andre, Sao Paulo State, Brazil. FAU - Damasceno, Debora Cristina AU - Damasceno DC AD - Laboratory of Experimental Research on Gynecology and Obstetrics, Postgraduate Course on Tocogynecology, Botucatu Medical School, Sao Paulo State University (Unesp), Botucatu, Sao Paulo State, Brazil. LA - eng PT - Journal Article PT - Research Support, Non-U.S. Gov't PL - United States TA - Biol Reprod JT - Biology of reproduction JID - 0207224 SB - IM MH - Animals MH - Congenital Abnormalities/*etiology/metabolism MH - Diabetes Mellitus, Experimental/*complications/metabolism MH - Embryo Implantation/physiology MH - Embryonic Development/*physiology MH - Female MH - Oxidative Stress/physiology MH - Rats MH - Rats, Sprague-Dawley OTO - NOTNLM OT - fetus OT - hyperglycemia OT - oxidative stress OT - pregestational OT - rat EDAT- 2020/09/02 06:00 MHDA- 2021/10/21 06:00 CRDT- 2020/09/02 06:00 PHST- 2020/05/05 00:00 [received] PHST- 2020/08/12 00:00 [revised] PHST- 2020/08/22 00:00 [accepted] PHST- 2020/09/02 06:00 [pubmed] PHST- 2021/10/21 06:00 [medline] PHST- 2020/09/02 06:00 [entrez] AID - 5900057 [pii] AID - 10.1093/biolre/ioaa151 [doi] PST - ppublish SO - Biol Reprod. 2020 Oct 29;103(5):938-950. doi: 10.1093/biolre/ioaa151.