Four years of the COVID-19 pandemic: how does Brazil deal with the impacts? A DOHaD perspective.

Over the last few years, during the pandemic, the Brazilian population has suffered several problems, ranging from health to socioeconomic impacts. When we consider Brazilian science, there has been an undeniable scientific delay generated by the pandemic, especially in areas that are not related to the coronavirus. In this context, with the aim of fostering collaboration among researchers in the field of Developmental Origins of Health and Diseases (DOHaD) and enhancing the potential for implementing public health strategies to prevent noncommunicable chronic diseases, the Brazilian Association of Developmental Origins of Health and Diseases (DOHaD Brazil) was established in 2020. In this narrative, we explore the effects of the COVID-19 pandemic in Brazil, focusing on its impacts on scientific research conducted in universities. Additionally, we underscore the significance of the DOHaD Brazil Association, particularly from the perspective of young researchers engaged in DOHaD research in Brazil.

Effect of transgenerational diabetes via maternal lineage in female rats.

Aim: To investigate the transgenerational effect of maternal hyperglycemia on oxidative stress markers, lipid profile, glycemia, pancreatic beta (ß)-cells, and reproductive outcomes in the F2 adult generation. Additionally, to expand the knowledge on transgenerational diabetes the F3 generation at birth will be evaluated. Methods: On day 5 of postnatal life female Sprague-Dawley rat newborns (F0 generation) were distributed into two groups: Diabetic (Streptozotocin-STZ, 70 mg/kg body weight, subcutaneous route) and Control rats. Adult female rats from the F0 generation and subsequently the F1 generation were mated to obtain the F2 generation, which was distributed into F2 generation (granddaughters) from control (F2_C) and diabetic (F2_D) rats. Oral Glucose Tolerance Test (OGTT), the area under the curve (AUC), blood biochemical analyses, and pancreatic morphology were analyzed before pregnancy. Reproductive outcomes were performed at the end of pregnancy. At birth, the glycemia and body weight of F3_C and F3_D rats were determined. p < 0.05 was considered significant. Results: F2_D had higher body weight, triglyceride levels, and percentage of insulin-immunostained cells, contributing to glucose intolerance, and insulin resistance before pregnancy. At day 21 of pregnancy, the F2_D showed increased embryonic losses before and after implantation (84.33 and 83.74 %, respectively). At birth, F3_D presented hyperglycemia, and 16.3 % of newborns were large for pregnancy age (LGA). Conclusion: Diabetes induction since the neonatal period in the first generation (F0) led to transgenerational (F2 and F3 generations) changes via the maternal lineage of female rats, confirming the relevance of control strictly the glycemia all the time.

Toxicological effects of the Curatella americana extract in embryo development of female pups from diabetic rats.

Maternal diabetes can influence the development of offspring during fetal life and postnatally. Curatella americana is a plant used as a menstrual cycle regulator and to prevent diabetes. This study evaluates the effects of C. americana aqueous extract on the estrous cycle and preimplantation embryos of adult female pups from diabetic rats. Female Sprague Dawley newborn rats received Streptozotocin or vehicle (citrate buffer). At adulthood, were submitted to the Oral Glucose Tolerance Test, and mated. The female rats were obtained and were distributed into four experimental groups: OC and OC/T represent female pups of control mothers and received water or plant extract, respectively; OD and OD/T represent female pups of diabetic mothers and received water or plant extract, respectively. The estrous cycle was followed for 10 days, the rats were mated and on gestational day 4 was performed preimplantation embryo analysis. Phenolic composition and biogenic amines in the extract were analyzed about the influence of the thermal process. The female pups from diabetic dams exhibited glucose intolerance, irregular estral cycle and a higher percentage of pre-embryos in delayed development (morula stage). After C. americana treatment, OD/T group no present a regular estrous cycle. Furthermore, the infusion process increases phenolic compounds and biogenic amines levels, which can have anti-estrogenic effect, anticipates the early embryonic development, and impair pre-implantation embryos. Thus, the indiscriminate use of medicinal plants should be avoided in any life phases by women, especially during pregnancy.

Maternal-fetal toxicity of Strychnos pseudoquina extract treatment during pregnancy.

ETHNOPHARMACOLOGICAL RELEVANCE: Plants and herbs have been used by women throughout history for therapeutic purposes. Strychnos pseudoquina, a plant used in the treatment of various diseases, can also function as an abortive herb. There is no scientific confirmation of its effects during pregnancy, and the activity of this plant needs to be substantiated or refuted with experimental evidence. AIM OF THE STUDY: Evaluating the effect of the S. pseudoquina aqueous extract on maternal reproductive toxicity and fetal development. MATERIALS AND METHODS: The aqueous extract of S. pseudoquina bark was evaluated in Wistar rats. Pregnant rats were distributed into four experimental groups (n = 12 rats/group): Control = treated with water (vehicle); Treated 75, Treated 150, and Treated 300 = treated with S. pseudoquina at dose 75, 150 and 300 mg/kg, respectively. The rats were treated by an intragastric route (gavage) from day 0 to day 21 of pregnancy. At the end of pregnancy, maternal reproductive outcomes, organs, biochemical and hematological profiles, fetuses, and placentas were analyzed. Maternal toxicity was evaluated through body weight gain, water, and food intake. With knowledge of the harmful dosage of the plant, other rats were used on gestational day 4 for the evaluation of morphological analyses before embryo implantation. P < 0.05 was considered as statistically significant. RESULTS: The S. pseudoquina treatment showed elevated liver enzymatic activities. The Treated 300 group presented toxicity with reduced maternal body weight, water and food intake, and increased kidney relative weight compared to those of the Control group. At a high dosage, the plant presents an abortifacient activity, confirmed by embryo losses before and after implantation and degenerated blastocysts. In addition, the treatment contributed to an increased percentage of fetal visceral anomalies, decreased ossification sites, and intrauterine growth restriction (300 mg/kg dose). CONCLUSION: In general, our study showed that an aqueous extract of S. pseudoquina bark caused significant abortifacient activity that testified to its traditional use. Furthermore, the S. pseudoquina extract caused maternal toxicity that contributed to impaired embryofetal development. Therefore, the use of this plant should be completely avoided during pregnancy to prevent unintended abortion and risks to maternal-fetal health.

Calcium Supplementation on Glucose Tolerance, Oxidative Stress, and Reproductive Outcomes of Diabetic Rats and Their Offspring.

Diabetes mellitus increases the risk of obstetric complications, morbidity, and infant mortality. Controlled nutritional therapy with micronutrients has been employed. However, the effect of calcium (Ca2+) supplementation on diabetic pregnancy is unclear. We aimed to evaluate whether diabetic rats supplemented with Ca2+ during pregnancy present better glucose tolerance, redox status, embryonic and fetal development, newborn weight, and the prooxidant and antioxidant balance of male and female pups. For this, newborn rats received the beta-cytotoxic drug streptozotocin for inducing diabetes on the day of birth. In adulthood, these rats were mated and treated with Ca2+ twice a day from day 0 to day 20 of pregnancy. On day 17, the pregnant rats were submitted to the oral glucose tolerance test (OGTT). At the end of pregnancy, they were anesthetized and killed to collect blood and pancreas samples. The uterine horns were exposed for an evaluation of maternal reproductive outcomes and embryofetal development, and the offspring's liver samples were collected for redox status measurement. Nondiabetic and diabetic rats supplemented with Ca2+ showed no influence on glucose tolerance, redox status, insulin synthesis, serum calcium levels, and embryofetal losses. The reduced rate of newborns classified as adequate for gestational age (AGA) and higher rates of LGA (large) and small (LGA) newborns and higher -SH and GSH-Px antioxidant activities in female pups were observed in diabetic dams, regardless of supplementation. Thus, maternal supplementation caused no improvement in glucose tolerance, oxidative stress biomarkers, embryofetal growth and development, and antioxidants in pups from diabetic mothers.

Severe Diabetes Induction as a Generational Model for Growth Restriction of Rat.

We used uncontrolled maternal diabetes as a model to provoke fetal growth restriction in the female in the first generation (F1) 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 (F2). For this, nondiabetic and streptozotocin-induced severely diabetic Sprague-Dawley rats were mated to obtain female pups (F1), which were classified as adequate (AGA) or small (SGA) for gestational weight. Afterward, we composed two groups: F1 AGA from nondiabetic dams (Control) and F1 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 (F1 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 F1 generation, oxidative stress status was observed in the maternal liver and blood samples. In addition, their offspring (F2 generation) had lower fetal weight and placental efficiency, regardless of gender, which caused fetal growth restriction and confirmed the fetal programming influence.

Toxicological effects of the Morinda citrifolia L. fruit extract on maternal reproduction and fetal development in rats.

Morinda citrifolia L., also known as Noni, is widely used plant in folk medicine for various therapeutic purposes. However, reports on its effects during pregnancy are limited. Therefore, the objective of this study was to evaluate the effects of the M. citrifolia fruit extract on maternal performance and fetal development during pregnancy in rats. Pregnant Wistar rats (n = 12/group) were treated from gestational days (GD) 0-21 with water (control group) or the aqueous extract of M. citrifolia fruit at doses of 200, 400, or 750 mg/kg, orally. During pregnancy, clinical signs of toxicity, maternal weight, feed intake, and water consumption were noted. On GD 21, the rats were anesthetized and blood was collected to evaluate various biochemical parameters. During laparotomy, reproductive performance parameters were recorded, and fetuses were weighed and the anomalies analyzed. Reduced placental efficiency and fetal growth restriction were observed in the group treated with 400 mg/kg of M. citrifolia extract. The highest dose (750 mg/kg) augmented aspartate aminotransferase concentration and preimplantation losses, while reducing the number of live fetuses. Furthermore, both doses (400 and 750 mg/kg) of the plant extract caused fetal anomalies. In conclusion, consumption of high doses of the M. citrifolia aqueous extrac during pregnancy leads to maternal hepatotoxicity, anti-implantation effects, intrauterine growth restriction and fetal abnormalities, indicating that the plant fruit extract can be harmful to both the mother and the fetus.

Nonpregnant and pregnant adult female rats affected by maternal diabetes environment.

Maternal diabetes-mediated fetal programming is widely discussed, however, it is important to define the extent to which intrauterine hyperglycemia interferes with the health of female pups, along with determining whether these changes can be perpetuated across generations. This study aimed to evaluate the effects of maternal diabetes on fetal programming and the repercussions on the metabolism of pregnant and nonpregnant female pups. Diabetes status was induced (diabetic group-D) using streptozotocin (a beta cell cytotoxic drug) on the fifth postnatal day of female rats, while controls received a citrate buffer (Control-C). In adulthood, the rats were mated to obtain their female pups. At 90 days of age, half of the female pups were mated (preg) and the other half continued virgin (Npreg). Furthermore, they were distributed into four groups: OC/Npreg and OC/preg-female pups from control mothers; OD/Npreg and OD/preg-female pups from diabetic mothers. At 115 days of life and/or 17 days of pregnancy, the oral glucose tolerance test (OGTT) was performed with blood collection for insulin measurement. At 120 days of life and/or 21 days of pregnancy, the rats were anesthetized and euthanized to determine their blood oxidative stress status. The OD/Npreg group showed glucose intolerance during OGTT (p < 0.0001), while the OD/preg group showed increased insulin secretion during OGTT (p < 0.0001) and insulin resistance (IR; p = 0.0027). An increase in homeostatic model assessment ß was shown in the pregnant groups, regardless of maternal diabetes (p < 0.0001). The OD/preg group presented increased thiobarbituric acid reactive substances (p < 0.0001) and -SH levels (p = 0.0005) and decreased superoxide dismutase activity (p = 0.0063). Additionally, small fetuses for gestational age (p < 0.0001) were found in these rats. In conclusion, exposure to maternal hyperglycemia compromises the glycemic metabolism of female pups before and during pregnancy and causes oxidative stress, IR, and impaired fetal growth during pregnancy.

Phytochemical and antidiabetic analysis of Curatella americana L. aqueous extract on the rat pregnancy.

ETHNOPHARMACOLOGICAL RELEVANCE: Curatella americana L. is employed in popular medicine for treating diabetes. However, the understanding around its outcomes during pregnancy is unclear. AIM OF THE STUDY: To evaluate the phytochemical and hypoglycemic analysis of the C. americana extract and its maternal-fetal effect on diabetic rats. MATERIALS AND METHOD: Diabetes was chemically induced 24 h after birth in Wistar female newborn rats. At adulthood, after diabetes status confirmation, the rats were mated and randomized into four experimental groups: Nondiabetic (Control): given water; Treated: given C. americana extract; Diabetic, and Treated Diabetic rats. The aqueous extract of C. americana leaves (300 mg/kg) was administered daily through oral route during pregnancy. Maternal toxicity and biochemical profile, reproductive outcomes, fetal development, and phenolic composition and biogenic amines in aqueous extract were analyzed. RESULTS AND CONCLUSION: Phytochemical analysis revealed that the main phenolic components are 3-hydroxytyrosol, kaempferol, and quercetin, while tryptophan and putrescine derivatives were identified as the dominant amines. C. americana extract treatment improved the lipid profile, although no effect on hyperglycemic control in diabetic rats was observed. Maternal diabetes or C. americana extract caused embryo losses confirmed by the lower number of pre-embryos in early pregnancy and higher percentage of abnormal morphologically pre-embryos. C. americana extract previously caused premature pre-embryo fixation before implantation window in nondiabetic and diabetic mothers and intrauterine growth restriction in the fetuses of treated nondiabetic dams, complicating the embryo fetal development. These findings reinforce the caution of indiscriminate use of medicinal plants, especially during pregnancy.