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We used uncontrolled maternal diabetes as a model to provoke fetal growth restriction in the female in the first generation (F 1 ) and to evaluate reproductive outcomes and the possible changes in metabolic systems during pregnancy, as well as the repercussions at birth in the second generation (F 2 ). For this, nondiabetic and streptozotocin-induced severely diabetic Sprague-Dawley rats were mated to obtain female pups (F 1 ), which were classified as adequate (AGA) or small (SGA) for gestational weight. Afterward, we composed two groups: F 1 AGA from nondiabetic dams (Control) and F 1 SGA from severely diabetic dams (Restricted) (n minimum = 10 animals/groups). At adulthood, these rats were submitted to the oral glucose tolerance test, mated, and at day 17 of pregnancy, blood samples were collected to determine glucose and insulin levels for assessment of insulin resistance. At the end of the pregnancy, the blood and liver samples were collected to evaluate redox status markers, and reproductive, fetal, and placental outcomes were analyzed. Maternal diabetes was responsible for increased SGA rates and a lower percentage of AGA fetuses (F 1 generation). The restricted female pups from severely diabetic dams presented rapid neonatal catch-up growth, glucose intolerance, and insulin resistance status before and during pregnancy. At term pregnancy of F 1 generation, oxidative stress status was observed in the maternal liver and blood samples. In addition, their offspring (F 2 generation) had lower fetal weight and placental efficiency, regardless of gender, which caused fetal growth restriction and confirmed the fetal programming influence., (© 2023. The Author(s), under exclusive licence to Society for Reproductive Investigation.)

Studies on vitamin D supplementation have been performed in experimental and clinical investigations considering gestational diabetes and/or vitamin D deficiency in pregnancy. However, the results are controversial and few present the effects and mechanisms of this micronutrient on pregestational diabetes. The objective of this study was to evaluate the effect of vitamin D on the pregnancy of rats with pre-existing diabetes and their fetuses. Pregestational diabetes was induced in Sprague-Dawley rats at birth. The adult diabetic and nondiabetic rats were orally administered with vitamin D (cholecalciferol) throughout the pregnancy. The diabetes status was monitored during pregnancy by an oral glucose tolerance test (OGTT). At the end of the pregnancy, pancreas and blood samples were collected for morphological analyses and lipid peroxidation measurements, respectively. The influence of vitamin D treatment on reproductive outcomes, fetal growth, and development were compared to those of untreated diabetic and nondiabetic pregnant rats. P < 0.05 was considered a significant statistical limit. The diabetic rats given vitamin D had a greater number of insulin-positive cells, contributing to reduced blood glucose levels and thiobarbituric acid reactive substance concentrations (TBARS-an indicator of membrane lipid peroxidation), and increased reduced thiol group levels, contributing to suitable intrauterine conditions for better fetal development, which was confirmed by higher fetal viability rates. Thus, this study shows the effects and mechanisms of vitamin D supplementation on pre-existing diabetes in pregnant rats, confirming its beneficial effects on maternal redox status and glycemic control, and the decline of adverse maternal-fetal repercussions., (© 2022. The Author(s), under exclusive licence to Society for Reproductive Investigation.)

Pregestational hyperglycemia cause adverse effects on mothers and their offspring. We aimed to evaluate the maternal hyperglycemia influence on pre-embryos from diabetic rats and on their generations (daughters and granddaughters). Diabetes was induced in Sprague-Dawley rats. The mothers and their female pups were submitted to oral glucose tolerance test in adulthood. In day 4 of pregnancy, pre-embryos were collected for morphological analysis. The diabetic mother, daughter and granddaughter rats showed glucose intolerance and their pre-embryos presented developmental delay, degeneration and losses compared to the nondiabetic group. Thus, maternal diabetes transgenerationally affects embryos at early development, which contributes for embryofetal losses.

Clinical and epidemiological studies show that maternal hyperglycemia can change the programming of offspring leading to transgenerational effects. These changes may be related to environmental factors, such as high-fat diet (HFD) consumption, and contribute to the comorbidity onset at the adulthood of the offspring. The objective of this study was to evaluate the hyperglycemic intrauterine environment, associated or not with an HFD administered from weaning to adult life on the periovarian adipose tissue of rat offspring Maternal diabetes was chemically induced by Streptozotocin. Female offsprings were randomly distributed into four experimental groups (n = 5 animals/group): Female offspring from control or diabetic mothers and fed an HFD or standard diet. HFD was prepared with lard enrichment and given from weaning to adulthood. On day 120 of life, the rats were anesthetized and sacrificed to obtain adipose tissue samples. Then, the hyperglycemic intrauterine environment and HFD fed after weaning caused a higher body weight, total fat, and periovarian fat in adult offspring, which could compromise the future reproductive function of these females. These rats showed higher adiposity index and adipocyte area, contributing to hypertrophied adipose tissue. Therefore, maternal diabetes itself causes intergenerational changes and, in association with the HFD consumption after weaning, exacerbated the changes in the adipose tissue of adult female offspring.

The presence of diabetes in pregnancy leads to hormonal and metabolic changes making inappropriate intrauterine environment, favoring the onset of maternal and fetal complications. Human studies that explore mechanisms responsible for changes caused by diabetes are limited not only for ethical reasons but also by the many uncontrollable variables. Thus, there is a need to develop appropriate experimental models. The diabetes induced in laboratory animals can be performed by different methods depending on dose, route of administration, and the strain and age of animal used. Many of these studies are carried out in neonatal period or during pregnancy, but the results presented are controversial. So this paper, addresses the review about the different models of mild diabetes induction using streptozotocin in pregnant rats and their repercussions on the maternal and fetal organisms to propose an adequate model for each approached issue.