Periodontitis and diabetes in pregnant rats: Maternal-fetal outcomes.

Aim: To evaluate the repercussions of periodontitis and diabetes association on rat pregnancy and newborns. Methods: Diabetes was induced in female Wistar rats 24 h after birth through the administration of Streptozotocin. The diabetic condition of the rats was further confirmed in adulthood. After mating, the pregnant rats were distributed into four experimental groups (n = 12 rats/group): nondiabetic and diabetic with and without periodontitis. Periodontitis was induced by a ligature inserted into the first molar on day 0 of pregnancy. Body weight, water and feed consumption were evaluated weekly, and an oral glucose tolerance test was performed on day 17 of pregnancy. On day 21 of pregnancy, the animals were anesthetized and killed for organ removal. The hemimandibles were collected to analyze alveolar bone loss. Immunological and biochemical parameters were evaluated in the maternal blood samples, and reproductive performance was analyzed. The newborns were weighed, and anomalies evaluated. Results: The group with diabetes and periodontitis had a greater degree of alveolar bone loss, along with higher relative pancreatic weight, blood glucose levels, triglyceride and inflammatory cytokine levels, hepatic transaminase activity, and embryonic losses. In addition, these newborns had increased body weight, placental weight, a greater number of ossification centers, and a higher rate of visceral and skeletal anomalies. Conclusion: The combination of maternal diabetes and periodontitis negatively impacts maternal parameters and fetal development. The findings reinforce the importance of maintaining maternal oral health to ensure the general health of the offspring, especially in cases where diabetes is present.

Phytochemical characterization and antidiabetic analysis of Bauhinia holophylla extract on the maternal-fetal outcomes of rats.

This study aims to evaluate the phytochemical properties of Bauhinia holophylla (Bong.) Steud leaf extract, and their impact on maternal reproductive and fetal development in diabetic rats. For this, adult female Wistar rats (100 days of life) received streptozotocin (40 mg/Kg, intraperitoneal) for induction of diabetes, were mated and distributed into four groups: Nondiabetic; Nondiabetic given B. holophylla; Diabetic; and Diabetic given B. holophylla. The plant extract was given by gavage at increasing doses: 200, 400, and 800 mg/Kg. At day 21 of pregnancy, liver and blood samples were obtained for oxidative parameters and biochemical analysis, respectively. The uterus was removed for maternal-fetal outcomes. Phytochemical analysis showed a high content of phenolic components and biogenic amines. B. holophylla extract did not alter the glycemic levels but improved the lipid profile in diabetic animals. Besides that, the number of live fetuses and maternal weight gain were decreased in Diabetic group, and were not observed in animals treated. The group Diabetic treated presented a higher percentage of fetuses classified as adequate for gestational age compared to the Diabetic group. However, the treatment with plant extract caused embryo losses, fetal growth restriction, and teratogenicity in nondiabetic rats. Thus, the indiscriminate consumption requires carefulness.

Intergenerational Hyperglycemia Impairs Mitochondrial Function and Follicular Development and Causes Oxidative Stress in Rat Ovaries Independent of the Consumption of a High-Fat Diet.

We analyzed the influence of maternal hyperglycemia and the post-weaning consumption of a high-fat diet on the mitochondrial function and ovarian development of the adult pups of diabetic rats. Female rats received citrate buffer (Control-C) or Streptozotocin (for diabetes induction-D) on postnatal day 5. These adult rats were mated to obtain female pups (O) from control dams (OC) or from diabetic dams (OD), and they received a standard diet (SD) or high-fat diet (HFD) from weaning to adulthood and were distributed into OC/SD, OC/HFD, OD/SD, and OD/HFD. In adulthood, the OGTT and AUC were performed. These rats were anesthetized and euthanized for sample collection. A high percentage of diabetic rats were found to be in the OD/HFD group (OD/HFD 40% vs. OC/SD 0% p < 0.05). Progesterone concentrations were lower in the experimental groups (OC/HFD 0.40 ± 0.04; OD/SD 0.30 ± 0.03; OD/HFD 0.24 ± 0.04 vs. OC/SD 0.45 ± 0.03 p < 0.0001). There was a lower expression of MFF (OD/SD 0.34 ± 0.33; OD/HFD 0.29 ± 0.2 vs. OC/SD 1.0 ± 0.41 p = 0.0015) and MFN2 in the OD/SD and OD/HFD groups (OD/SD 0.41 ± 0.21; OD/HFD 0.77 ± 0.18 vs. OC/SD 1.0 ± 0.45 p = 0.0037). The number of follicles was lower in the OD/SD and OD/HFD groups. A lower staining intensity for SOD and Catalase and higher staining intensity for MDA were found in ovarian cells in the OC/HFD, OD/SD, and OD/HFD groups. Fetal programming was responsible for mitochondrial dysfunction, ovarian reserve loss, and oxidative stress; the association of maternal diabetes with an HFD was responsible for the higher occurrence of diabetes in female adult pups.

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.

Effects of a maternal high-fat diet on adipose tissue in murine offspring: A systematic review and meta-analysis.

The aim of this systematic review and meta-analysis was to analyze the influence of a maternal and/or offspring high-fat diet (HFD) on the morphology of the offspring adipocytes and amount of food and energy consumption. The search was conducted through Pubmed, EMBASE, and Web of Science databases up to October 31st, 2021. The outcomes were extracted and pooled as a standardized mean difference with random effect models. 5,004 articles were found in the databases. Of these, only 31 were selected for this systematic review and 21 were included in the meta-analysis. A large discrepancy in the percentage of fat composing the HFD (from 14% to 62% fat content) was observed. Considering the increase of adipose tissue by hyperplasia (cell number increase) and hypertrophy (cell size increase) in HFD models, the meta-analysis showed that excessive consumption of a maternal HFD influences the development of visceral white adipose tissue in offspring, related to adipocyte hypertrophy, regardless of their HFD or control diet consumption. Upon following a long-term HFD, hyperplasia was confirmed in the offspring. When analyzing the secondary outcome in terms of the amount of food and energy consumed, there was an increase of caloric intake in the offspring fed with HFD whose mothers consumed HFD. Furthermore, the adipocyte hypertrophy in different regions of the adipose tissue is related to the sex of the pups. Thus, the adipose tissue obesity phenotypes in offspring are programmed by maternal consumption of a high-fat diet, independent of postnatal diet.

Maternal Diabetes and Postnatal High-Fat Diet on Pregnant Offspring.

Maternal diabetes-induced fetal programming predisposes offspring to type 2 diabetes, cardiovascular disease, and obesity in adulthood. However, lifelong health and disease trajectories depend on several factors and nutrition is one of the main ones. We intend to understand the role of maternal diabetes-induced fetal programming and its association with a high-fat diet during lifelong in the female F1 generation focusing on reproductive outcomes and the possible changes in physiological systems during pregnancy as well as the repercussions on the F2 generation at birth. For this, we composed four groups: F1 female pups from control (OC) or from diabetic dams (OD) and fed with standard (SD) or high-fat diet from weaning to full-term pregnancy. During pregnancy, glucose intolerance and insulin sensitivity were evaluated. In a full-term pregnancy, the maternal blood and liver were collected to evaluate redox status markers. The maternal blood, placental tissue, and fetal blood (pool) were collected to evaluate adiponectin and leptin levels. Maternal reproductive parameters were evaluated as well. Maternal diabetes and high-fat diet consumption, in isolation, were both responsible for increased infertility rates and fasting glucose levels in the F1 generation and fetal growth restriction in the F2 generation. The association of both conditions showed, in addition to those, increased lipoperoxidation in maternal erythrocytes, regardless of the increased endogenous antioxidant enzyme activities, glucose intolerance, decreased number of implantation sites and live fetuses, decreased litter, fetal and placental weight, increased preimplantation losses, and increased fetal leptin serum levels. Thus, our findings show that fetal programming caused by maternal diabetes or lifelong high-fat diet consumption leads to similar repercussions in pregnant rats. In addition, the association of both conditions was responsible for glucose intolerance and oxidative stress in the first generation and increased fetal leptin levels in the second generation. Thus, our findings show both the F1 and F2 generations harmed health after maternal hyperglycemic intrauterine environment and exposure to a high-fat diet from weaning until the end of pregnancy.

Oxidative Stress Profile of Mothers and Their Offspring after Maternal Consumption of High-Fat Diet in Rodents: A Systematic Review and Meta-Analysis.

Maternal exposure to the high-fat diet (HFD) during gestation or lactation can be harmful to both a mother and offspring. The aim of this systematic review was to identify and evaluate the studies with animal models (rodents) that were exposed to the high-fat diet during pregnancy and/or lactation period to investigate oxidative stress and lipid and liver enzyme profile of mothers and their offspring. The electronic search was performed in the PUBMED (Public/Publisher MEDLINE), EMBASE (Ovid), and Web of Science databases. Data from 77 studies were included for qualitative analysis, and of these, 13 studies were included for meta-analysis by using a random effects model. The pooled analysis revealed higher malondialdehyde levels in offspring of high-fat diet groups. Furthermore, the pooled analysis showed increased reactive oxygen species and lower superoxide dismutase and catalase in offspring of mothers exposed to high-fat diet during pregnancy and/or lactation. Despite significant heterogeneity, the systematic review shows oxidative stress in offspring induced by maternal HFD.

Congenital Anomalies Programmed by Maternal Diabetes and Obesity on Offspring of Rats.

Embryo-fetal exposure to maternal disorders during intrauterine life programs long-term consequences for the health and illness of offspring. In this study, we evaluated whether mild diabetic rats that were given high-fat/high-sugar (HF/HS) diet presented maternal and fetal changes at term pregnancy. Female rats received citrate buffer (non-diabetic-ND) or streptozotocin (diabetic-D) after birth. According to the oral glucose tolerance test (OGTT), the experimental groups (n = 11 animals/group) were composed of non-diabetic and diabetic receiving standard diet (S) or HF/HS diet. High-fat/high-sugar diet (30% kcal of lard) in chow and water containing 5% sucrose and given 1 month before mating and during pregnancy. During and at the end of pregnancy, obesity and diabetes features were determined. After laparotomy, blood samples, periovarian fat, and uterine content were collected. The diabetic rats presented a higher glycemia and percentage of embryonic losses when compared with the NDS group. Rats DHF/HS presented increased obesogenic index, caloric intake, and periovarian fat weight and reduced gravid uterus weight in relation to the other groups. Besides, this association might lead to the inflammatory process, confirmed by leukocytosis. Obese rats (NDHF/HS and DHF/HS) showed higher triglyceride levels and their offspring with lower fetal weight and ossification sites, indicating intrauterine growth restriction. This finding may contribute to vascular alterations related to long-term hypertensive disorders in adult offspring. The fetuses from diabetic dams showed higher percentages of skeletal abnormalities, and DHF/HS dams still had a higher rate of anomalous fetuses. Thus, maternal diabetes and/or obesity induces maternal metabolic disorders that contribute to affect fetal development and growth.

Maternal and Fetal-Placental Effects of Etanercept Treatment During Rats' Pregnancy.

Etanercept is a tumor necrosis factor alpha (TNF-α) inhibitor chronically used to treat autoimmune diseases. However, the use of etanercept during pregnancy still needs to be further investigated. The aim of this study is to evaluate the etanercept treatment during pregnancy, analyzing maternal reproductive performance, fetal outcomes, and placental repercussions. Wistar rats (200-250 g) were mated and randomly distributed into two experimental groups: control and etanercept (n = 10 animals/group). Treatments with etanercept (0.8 mg/kg, s.c.), or saline (control group) were carried out on days 0, 6, 12, and 18 of gestation. On the morning of the 21st day of pregnancy, rats were euthanized in a CO2 chamber and submitted to laparotomy to remove the fetuses, placentas, ovaries, and maternal organs. There were no differences between groups in the following parameters: water and food consumption; placental efficiency; reproductive parameters, including number of corpora lutea and implants, reabsorption, and pre- and post-implantation losses. However, etanercept treatment increased liver weight, reduced fetal and placental weight, decreased the placental junction zone, reduced the percentage of normal fetuses, and increased visceral or skeletal fetal abnormalities. Therefore, etanercept resulted in damages more related to fetus and placenta. However, more studies with different doses are required to better predict possible injuries elicited using etanercept during pregnancy.

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

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.

Streptozotocin-induced leukocyte DNA damage in rats.

Although several studies using peripheral blood samples suggest that DNA damage is caused by streptozotocin (STZ) per se, our hypothesis is that DNA damage is caused by STZ-induced glycemic changes. Thus, we aimed at evaluating DNA damage levels in peripheral blood samples from rats at different time points within the first 24 h after a single intravenous dose of STZ. Female Wistar rats (control, n = 8; STZ, n = 7) were administered a single STZ intravenous injection (40 mg/kg body weight). Blood samples were collected from the tail vein for genotoxicity analysis by comet assay and glycemia assessment before STZ administration (time point zero) and at 2, 4, 6, 8, 12, and 24 h afterward. At 2 h, there was initial hyperglycemia associated with STZ-induced glycogenolysis that caused an increase in leukocyte DNA damage levels. At 4 h, glycemic and DNA damage levels were normalized. However, at 6 and 8 h, we observed hypoglycemia concomitant with increased DNA damage levels. From 10 h onward up to 24 h, DNA damage persisted and hyperglycemia appeared. Thus, DNA damage increased soon after both hypoglycemia and hyperglycemia, which were not directly induced by STZ owing to its known short life. In conclusion, increased peripheral blood DNA damage levels within 24 h after STZ administration in rats are associated with abnormal glycemic levels and their complications rather than with STZ per se.

Temporal analysis of distribution pattern of islet cells and antioxidant enzymes for diabetes onset in postnatal critical development window in rats.

AIM: At performing a temporal analysis of the distribution pattern of islet endocrine cells and antioxidant enzymes in diabetic rats during the post-natal critical development window. MAIN METHODS: The newborns received streptozotocin (STZ) at birth for diabetes induction, and control females received the vehicle. The animals were euthanized at different lifetimes: D5, D10, D15, and D30. Morphological analysis of pancreas and biochemical assays was performed. KEY FINDINGS: The STZ-induced rats presented irregular shape of islet on D5 and there was an attempt to restore of this shape in other life moment studied. There was an increase progressive in islet area, however they maintained smaller than those of control rats, with lower labeling intensity for insulin, higher for glucagon and somatostatin, lower for SOD-1 was lower in the islets of the STZ-induced animals at all times studied and for GSH-Px in D10 and D30. SIGNIFICANCE: Although STZ-induced diabetic rats presented compensatory mechanisms to restore the mass of endocrine cells, this was not sufficient since these rats developed the diabetic state. This was confirmed by the oral glucose tolerance test from D30. In addition, the delta (δ)-cells presented ectopic location in islets, indicating a possible relationship for beta (ß)-cell mass restoration. There was a response of the pancreas to reduce the hyperglycemia in the first month of life. Furthermore, the cells from the endocrine pancreas of diabetic animals show a decline of antioxidant enzymatic, contributing to the increased susceptibility of cells to hyperglycemia-induced ROS in this postnatal critical development window.

Pancreatic islet response to diabetes during pregnancy in rats.

AIMS: The objective of this study was to assess the mechanisms underlying pancreatic islet adaptation in diabetic mothers and their pups. Additionally, the influence of pancreatic adaptations on maternal reproductive performance was also investigated. MAIN METHODS: Wistar rats were injected with streptozotocin for diabetes induction. At adulthood (3 months), all animals underwent an oral glucose tolerance test (OGTT) for glucose assessment as an inclusion criterion. Following, the animals were mated. At day 18 of pregnancy, the mothers were killed for blood collect ion to determine fasting insulin and glucagon concentrations. The pancreas was removed and processed for the immunohistochemical analysis of insulin, glucagon, somatostatin, Ki-67 and PDX-1, superoxide dismutase 1 (SOD-1), glutathione peroxidase (GSH-Px) and malondialdehyde (MDA). The pregnant uterus was also collected for the evaluation of embryofetal loss. KEY FINDINGS: The diabetic rats showed increased glucose, serum glucagon and insulin concentrations, and embryofetal loss rates. They also showed a reduction in pancreatic islets area and percentage of cells stained for insulin, increased the percentage of non-ß cells (alpha e delta cells) stained for Ki-67, glucagon, and somatostatin. Moreover, the cells stained for somatostatin were spread across the islets and showed stronger staining for MDA and weaker staining for GSH-Px. SIGNIFICANCE: Diabetes leads to adaptive responses from the endocrine pancreas in pregnancy that especially involves non-ß cells, modifying the mantle-core structure. Nonetheless, these adaptations are not enough for glucose homeostasis and affect the maternal environment, which in turn impairs fetal development.

O-GlcNAc Modification During Pregnancy: Focus on Placental Environment.

Successful placentation is a key event for fetal development, which commences following embryo implantation into the uterine wall, eliciting decidualization, placentation, and remodeling of blood vessels to provide physiological exchange between embryo-fetus and mother. Several signaling pathways are recruited to modulate such important processes and specific proteins that regulate placental function are a target for the glycosylation with O-linked ß-N-acetylglucosamine (O-GlcNAc), or O-GlcNAcylation. This is a reversible post-translational modification on nuclear and cytoplasmic proteins, mainly controlled by O-GlcNAc transferase (OGT) and O-GlcNAcase (OGA). O-GlcNAcylation has been implicated as a modulator of proteins, both in physiological and pathological conditions and, more recently, O-GlcNAc has also been shown to be an important modulator in placental tissue. In this mini-review, the interplay between O-GlcNAcylation of proteins and placental function will be addressed, discussing the possible implications of this post-translational modification through placental development and pregnancy.

Effect of the induction of transgenerational obesity on maternal-fetal parameters.

Maternal obesity can cause complications for both women and their offspring for generations. Therefore, we intended to verify the repercussions of induction of transgenerational obesity on biochemical parameters, reproductive performance, and congenital anomaly frequency in Wistar rats. Female rats were used from successive generations. The female rats of parental generation (F0, n=10) were mated to obtain their offspring (F1 generation). F1 female rats received a monosodium glutamate (MSG) solution to induce obesity (n=07) or vehicle (control, n=06) during the neonatal period. These adult female rats were classified as normal or obese using the Lee Index, mated, and delivered offspring (F2 generation), which were also evaluated for obesity using the Lee Index in adult life (F2MSG, n=13, born from obese dams) or non-obesity status (F2Control, n=12, born from control dams), and were mated in adulthood. During pregnancy, glycemia and an oral glucose tolerance test (OGTT) were analyzed. At term pregnancy, the females were sacrificed for serum biochemical profile, maternal reproductive outcomes, and fetal development. In F2MSG rats, body weight gain at early pregnancy, glycemia by OGTT, total cholesterol, high-density-lipoprotein, and alanine transaminase activity were higher compared with those of F2Control rats. F2MSG rats also presented a lower implantation number and gravid uterus weight, increased pre-implantation loss and anomaly frequency in their fetuses (F3 generation) compared with those of F2Control rats. Therefore, even without significant changes in body weight gain, obesity was established at the end of pregnancy of Wistar rats using other biomarkers. Additionally, these rats showed multiple adverse reproductive outcomes, confirming the deleterious effects that lead to obesity.

Beneficial effects of Hibiscus rosa-sinensis L. flower aqueous extract in pregnant rats with diabetes.

PURPOSE: The Hibiscus rosa-sinensis flower is widely used in Brazilian traditional medicine for the treatment of diabetes and has shown antifertility activity in female Wistar rats. However, there is no scientific confirmation of its effect on diabetes and pregnancy. The aim of this study was evaluate the effect of aqueous extract of H. rosa-sinensis flowers on maternal-fetal outcome in pregnant rats with diabetes. METHODS: Diabetes was induced by streptozotocin (STZ, 40 mg/kg) in virgin, adult, female Wistar rats. After diabetes induction, the rats were mated. The pregnant rats were distributed into four groups (n minimum = 11 animals/group): non-diabetic, non-diabetic treated, diabetic, and diabetic treated. Oral aqueous extract of Hibiscus rosa-sinensis was administered to rats in the treatment groups during pregnancy. At term pregnancy, maternal reproductive outcomes, fetal parameters, and biochemical parameters were analyzed. RESULTS: The non-diabetic treated group showed decreased high density lipoprotein cholesterol, increased atherogenic index (AI) and coronary artery risk index (CRI), and increased preimplantation loss rate compared to the non-diabetic group. Although treatment with H. rosa-sinensis led to no toxicity, it showed deleterious effects on cardiac and reproductive functions. However, the diabetic treated group showed increased maternal and fetal weights, reduced AI and CRI, and reduced preimplantation loss rate compared to the untreated diabetic group. CONCLUSION: Our results demonstrate beneficial effects of this flower only in pregnant rats with diabetes and their offspring. Although these findings cannot be extrapolated to human clinical use, they show that the indiscriminate intake of H. rosa-sinensis may be harmful to healthy individuals and its use should be completely avoided in pregnancy.

Medicinal Plants for Diabetes Treatment During Pregnancy.

Diabetes mellitus is a syndrome of great importance that affects an increasing number of people every day. In particular, diabetes is a common and important disease during pregnancy and is marked by complications, both fetal and maternal, that increase the risks of morbidity and mortality for diabetic pregnant women and their offspring. Drugs such as insulin and hypoglycemic drugs are given to treat diabetes, but regular exercise and adequate diet have also been indicated. Furthermore, coadjutant therapies such as medicinal plants are popularly used to reduce diabetes-induced hyperglycemia, either within or outside the context of pregnancy. However, studies examining plant use for diabetes treatment are necessary to confirm its possible effects and its safety for the mother and fetus. The objective of this literature review was to conduct a survey of plant species that are utilized worldwide and their stated therapeutic uses. A literature search was performed using the terms "diabetes and pregnancy", which resulted in the identification of 31,272 articles. Of these studies, only 12 (0.0038%) were related to medicinal plants, demonstrating that there has been little investigation into this issue. Of the papers analyzed in this review, half evaluated plant leaves, indicating that these scientific studies attempted to reproduce the preparations commonly used by various populations, i.e., in the form of tea. Additionally, more than 90% of studies utilized experimental animals to evaluate the maternal-fetal safety of medicinal plant substances that may potentially be dangerous for humans. Thus, once confidence levels for plant-derived substances are established based on toxicological analyses and safety is confirmed, it is possible that plants will be used to complement conventional diabetes therapies.