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.

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 high-fat diet-induced diabetes on autophagy in the murine liver: A systematic review and meta-analysis.

AIMS: We conducted a meta-analysis to investigate whether diabetes induced by a high-fat diet (HFD) has the potential to alter the process of autophagy in the murine liver. METHODS: A systematic literature search was performed with electronic databases (PubMed, EMBASE, Web of Science). Study design, population, intervention, outcome, and risk of bias were analyzed. Given the availability of studies, a quantitative meta-analysis including 23 studies was performed. KEY FINDINGS: The search found 5754 articles, with 48 matching the eligibility criteria, comprising of 1033 animals. The meta-analysis showed that diabetic murines fed with HFD presented an absence of p62 degradation (SMD 4.63, 95 % CI 2.02 to 7.24, p = 0.0005; I2 = 77 %), higher expression of p-mTOR/mTOR (SMD 5.20, 95 % CI 1.00 to 9.39, p = 0.01; I2 = 78 %), and a decreased p-AMPK/AMPK ratio (SMD -2.02, 95 % CI -3.96 to -0.09, p = 0.04; I2 = 85 %) when compared to nondiabetic murines. When associated with streptozotocin, the animals presented decreased ATG-7 and LC3-II. The meta-regression results showed a decrease in autophagy responses due to increased glycemic levels, fat content, and long-term exposure to HFD, and advanced animal age. The common and species-specific protein responses were also consistent with the inhibition of autophagy. SIGNIFICANCE: The normal process of autophagy mechanisms in the liver is less competent after HFD consumption. The destabilization of (auto)phagolysosomes contributes to the perpetuation of diabetes, metabolic dysfunction-associated fatty liver disease, and cell death.

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.

Metabolic changes in female rats exposed to intrauterine hyperglycemia and postweaning consumption of high-fat diet†.

We evaluated the influence of the hyperglycemic intrauterine environment and postweaning consumption of a high-fat diet (HFD) on the glycemia, insulin, lipid, and immunological profile of rat offspring in adulthood. Female rats received citrate buffer (Control-C) or Streptozotocin (a beta cell-cytotoxic drug to induce diabetes-D) on postnatal day 5. In adulthood, these rats were mated to obtain female offspring, who were fed a standard diet (SD) or HFD from weaning to adulthood (n = 10 rats/group). OC/SD and OC/HFD represent female offspring of control mothers and received SD or HFD, respectively; OD/SD and OD/HFD represent female offspring of diabetic mothers and received SD or HFD, respectively. At adulthood, the oral glucose tolerance test (OGTT) was performed and, next, the rats were anesthetized and euthanized. Pancreas was collected and analyzed, and adipose tissue was weighted. Blood samples were collected to determine biochemical and immunological profiles. The food intake was lower in HFD-fed rats and visceral fat weight was increased in the OD/HFD group. OC/HFD, OD/SD, and OD/HFD groups presented glucose intolerance and lower insulin secretion during OGTT. An impaired pancreatic beta-cell function was shown in the adult offspring of diabetic rats, regardless of diet. Interleukin (IL)-6 and IL-10 concentrations were lower in the OD/HFD group and associated to a low-grade inflammatory condition. The fetal programming was responsible for impaired beta cell function in experimental animals. The association of maternal diabetes and postweaning HFD are responsible for greater glucose intolerance, impaired insulin secretion and immunological change.

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.

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.

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.

Contamination index. A novel parameter for metal and pesticide analyses in maternal blood and umbilical cord.

PURPOSE: To evaluate the contamination index of metals and pesticides in pregnant women, and to relate this to perinatal outcomes. METHODS: Descriptive, retrospective, exploratory study, developed from existing secondary data analyses at Level III maternity center. A total of 40 mothers with their newborns (NB), living in a rural area in Botucatu- Brazil and surrounding region. Blood samples from mothers and newborn were collected to determine the total contamination index for metals and pesticides. The concentrations of each metal and each pesticide were determined in blood samples of mothers and their newborns by Rudge's results. After obtaining these concentrations, the total contamination index in mother and NB was calculated, along with its correlation with clinical parameters of NB. RESULTS: There was no correlation (p> 0.05) between maternal contamination index with NB clinical parameters, and NB contamination index versus NB clinical parameters. CONCLUSION: The maternal contamination index of metals and pesticides was not related to perinatal outcomes, but it could be used as baseline parameter in future toxicological studies, regarding to long-term toxic characteristics as persistent organic pollutants, its long half-lives, bioacumulative, and expected to impose serious health effects on humans.

Role of sex hormones in gastrointestinal motility in pregnant and non-pregnant rats.

AIM: To correlate gastric contractility, gastrointestinal transit, and hormone levels in non-pregnant (estrous cycle) and pregnant rats using noninvasive techniques. METHODS: Female rats (n = 23) were randomly divided into (1) non-pregnant, (contractility, n = 6; transit, n = 6); and (2) pregnant (contractility, n = 5; transit, n = 6). In each estrous cycle phase or at 0, 7, 14, and 20 d after the confirmation of pregnancy, gastrointestinal transit was recorded by AC biosusceptometry (ACB), and gastric contractility was recorded by ACB and electromyography. After each recording, blood samples were obtained for progesterone and estradiol determination. RESULTS: In the estrous cycle, despite fluctuations of sex hormone levels, no significant changes in gastrointestinal motility were observed. Days 7 and 14 of pregnancy were characterized by significant changes in the frequency of contractions (3.90 ± 0.42 cpm and 3.60 ± 0.36 cpm vs 4.33 ± 0.25 cpm) and gastric emptying (168 ± 17 min and 165 ± 15 min vs 113 ± 15 min) compared with day 0. On these same days, progesterone levels significantly increased compared with control (54.23 ± 15.14 ng/mL and 129.96 ± 30.52 ng/mL vs 13.25 ± 6.31 ng/mL). On day 14, we observed the highest level of progesterone and the lowest level of estradiol compared with day 0 (44.3 ± 15.18 pg/mL vs 24.96 ± 5.96 pg/mL). CONCLUSION: Gastrointestinal motility was unaffected by the estrous cycle. In our data, high progesterone and low estradiol levels can be associated with decreased contraction frequency and slow gastric emptying.

Contamination index. A novel parameter for metal and pesticide analyses in maternal blood and umbilical cord

ABSTRACT PURPOSE: To evaluate the contamination index of metals and pesticides in pregnant women, and to relate this to perinatal outcomes. METHODS: Descriptive, retrospective, exploratory study, developed from existing secondary data analyses at Level III maternity center. A total of 40 mothers with their newborns (NB), living in a rural area in Botucatu- Brazil and surrounding region. Blood samples from mothers and newborn were collected to determine the total contamination index for metals and pesticides. The concentrations of each metal and each pesticide were determined in blood samples of mothers and their newborns by Rudge's results. After obtaining these concentrations, the total contamination index in mother and NB was calculated, along with its correlation with clinical parameters of NB. RESULTS: There was no correlation (p> 0.05) between maternal contamination index with NB clinical parameters, and NB contamination index versus NB clinical parameters. CONCLUSION: The maternal contamination index of metals and pesticides was not related to perinatal outcomes, but it could be used as baseline parameter in future toxicological studies, regarding to long-term toxic characteristics as persistent organic pollutants, its long half-lives, bioacumulative, and expected to impose serious health effects on humans.

Physiological and biochemical measurements before, during and after pregnancy of healthy rats.

PURPOSE: To analyze the physiological and biochemical measurements before, during and after pregnancy of healthy rats. METHODS: Wistar adult females rats (n=8) were weighed and blood samples were obtained before, during and after pregnancy for biochemical determinations, chow intake, water consumption and milk production were evaluated. At day 10 postpartum, the rats were killed for weighing of organs and adipose tissues. RESULTS: The results showed increase in body weight, serum insulin and ingestion of water and chow. At day 17 pregnancy, presented normal values in the OGTT. At days 7, 14 and 20 of pregnancy, there was increase in triglyceride levels. At term pregnancy, there was weight gain due to fetal growth. In the postpartum period presented reduced blood glucose levels. The glycemic means were reduced during and after pregnancy compared to after pregnancy. The triglyceride concentrations were increased before and during pregnancy in relation to after pregnancy. The total cholesterol levels presented no changes. CONCLUSION: The use of experimental animals is suitable for evaluation of metabolic changes because the profile of answers found in this study was similar to human profile, showing the relevance of translational research to better understand the pathophysiological mechanisms and possible treatment for diseases.

Physiological and biochemical measurements before, during and after pregnancy of healthy rats

PURPOSE:To analyze the physiological and biochemical measurements before, during and after pregnancy of healthy rats.METHODS:Wistar adult females rats (n=8) were weighed and blood samples were obtained before, during and after pregnancy for biochemical determinations, chow intake, water consumption and milk production were evaluated. At day 10 postpartum, the rats were killed for weighing of organs and adipose tissues.RESULTS: The results showed increase in body weight, serum insulin and ingestion of water and chow. At day 17 pregnancy, presented normal values in the OGTT. At days 7, 14 and 20 of pregnancy, there was increase in triglyceride levels. At term pregnancy, there was weight gain due to fetal growth. In the postpartum period presented reduced blood glucose levels. The glycemic means were reduced during and after pregnancy compared to after pregnancy. The triglyceride concentrations were increased before and during pregnancy in relation to after pregnancy. The total cholesterol levels presented no changes.CONCLUSION: The use of experimental animals is suitable for evaluation of metabolic changes because the profile of answers found in this study was similar to human profile, showing the relevance of translational research to better understand the pathophysiological mechanisms and possible treatment for diseases.

Oxidative stress status and placental implications in diabetic rats undergoing swimming exercise after embryonic implantation.

The potential benefits and risks of physical exercise on fetal development during pregnancy remain unclear. The aim was to analyze maternal oxidative stress status and the placental morphometry to relate to intrauterine growth restriction (IUGR) from diabetic female rats submitted to swimming program after embryonic implantation. Pregnant Wistar rats were distributed into 4 groups (11 animals/group): control-nondiabetic sedentary rats, control exercised-nondiabetic exercised rats, diabetic-diabetic sedentary rats, and diabetic exercised-diabetic exercised rats. A swimming program was used as an exercise model. At the end of pregnancy, the maternal oxidative stress status, placental morphology, and fetal weight were analyzed. The swimming program was not efficient to reduce the hyperglycemia-induced oxidative stress. This fact impaired placental development, resulting in altered blood flow and energy reserves, which contributed to a deficient exchange of nutrients and oxygen for the fetal development, leading to IUGR.