Abstract

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.

中文翻译：

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妊娠前糖尿病对大鼠早期胚胎相关胎儿畸形和生存能力的严重程度†。

摘要

既往/孕前糖尿病会增加出生缺陷的风险。植入过程中涉及多种因素，例如细胞因子（粒细胞-巨噬细胞-集落刺激因子 [GM-CSF]）。目的是在植入过程中评估两种水平的糖尿病对植入前胚胎氧化还原状态的影响，以了解两者如何参与胚胎和胎儿对母体糖尿病的生存能力。雌性 Sprague-Dawley 大鼠在出生时（轻度糖尿病 [MD]）或成年时（重度糖尿病 [SD]）接受链脲佐菌素，以获得两种实验性糖尿病强度。在确认糖尿病状态后，非糖尿病组和糖尿病组在生命的第 110 天左右交配。在妊娠日 (GD) 21，在植入前评估胎儿的生存能力和畸形以及卵巢的胚胎丢失。其他怀孕的非糖尿病和糖尿病大鼠在 GD2-4 处死，用于母体和植入前胚胎氧化应激标志物、母体血清胰岛素、子宫液 GM-CSF 和植入前胚胎形态分析。MD 和 SD 导致异常氧化还原水平，植入前期间 GM-CSF 和胰岛素水平降低，以及植入前胚胎丢失。SD 在 GD21 时导致较低的胎儿存活率和较高的胎儿畸形百分比。SD dam 来源的植入前胚胎在 GD3 时呈现较低的谷胱甘肽水平和较高的硫代巴比妥酸活性物质浓度，并且在 GD4 时异常植入前胚胎的频率增加。综上所述，先前存在的糖尿病会导致植入过程中出现并发症。此外，母体氧化应激和其他代谢变化会改变植入前胚胎的氧化还原状态和形态结构，导致妊娠晚期生长发育受损。