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.

Influence of maternal periuterine and periovarian fat on reproductive performance and fetal growth in rats.

We aimed to evaluate how high-fat diet consumption can interfere with rat reproductive performance and fetal development. High-fat diet (HFD) was initiated in 30-day-old rats, distributed into two groups (n=7 animals/group): Rats receiving a standard diet and rats receiving HFD. At adulthood, the rats were mated, and on day 21 of pregnancy, the females were anesthetized, decapitated, and submitted to laparotomy to obtain visceral and periovarian adipose tissue. The uterine horns were exposed for analysis of maternal reproductive performance. The fetuses and placentas were weighed and analyzed. Pearson's correlation test was used, and p<0.05 was considered significant. There was a significant positive correlation (HFD consumption x increased periovarian fat) and a negative correlation with the implantation, live fetus numbers and lower litter weight. Furthermore, the increased relative weight of periuterine fat was related to the lower number of live fetuses and litter weight. Regarding the fetal weight classification, there was a negative correlation between the relative weight of periovarian fat and the percentage of fetuses appropriate for gestational age and large for gestational age. Therefore, our findings show that HFD maternal intake negatively influenced on reproductive performance and fetal growth.

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.

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.

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.

Effects of short-term severe and long-term mild STZ-induced diabetes in urethral tissue of female rats.

AIMS: To estimate and compare the alterations in the urethral tissues of female rats with two diabetes models: short-term severe and long-term mild diabetes. METHODS: To induce mild diabetes (blood glucose levels between 120 and 300 mg/dl), female newborns received streptozotocin (100 mg/kg body weight, sc route), and to induce short-term severe diabetes (blood glucose levels > 300 mg/d), adult animals received streptozotocin (40 mg/kg, iv route). The rats were killed on day 133 of the experimental via an i.p. Thiopentax® injection of 80 mg/kg, and the urethrovaginal tissues were harvested. Morphometric, pathological, immunohistochemical, and ultrastructural analyses were conducted. RESULTS: In the long-term mild diabetes group, collagen deposition, severe fibrosis, lipid droplets and numerous subsarcolemmal, and intermyofibrillar mitochondria were observed. In the short-term severe diabetes group, centrally located myonuclei and a significantly reduced striated muscle area were noted. Both diabetic models exhibited similar immunohistochemistry patterns, with changes from fast to slow fibers and a decrease in the numbers of fast fibers. CONCLUSIONS: Either long-term mild hyperglycemia or short-term severe hyperglycemia have detrimental impacts on muscle health. They are both involved in the failure to maintain healthy skeletal muscle that may contribute to the development of pelvic floor dysfunctions via different pathways. These results have important implications for monitoring and prevention strategies for improving the quality of life of women with diabetes mellitus and pelvic floor muscle dysfunction. Neurourol. Urodynam. 36:574-579, 2017. © 2016 Wiley Periodicals, Inc.

Diet-Induced Weight Loss Reduces DNA Damage and Cardiometabolic Risk Factors in Overweight/Obese Women with Polycystic Ovary Syndrome.

AIMS: We aimed to investigate the impact of following a diet to induce weight loss (500 kcal deficit per day) over DNA damage and cardiometabolic risk factors in women with overweight/obesity diagnosed with polycystic ovary syndrome (PCOS). METHODS: A study was conducted in Natal, RN, Brazil selecting overweight/obese (body mass index ≥25 and <39 kg/m2) women (18-35 years). The levels of DNA damage were assessed by a single cell gel electrophoresis. Repeated 24 h dietary recall questionnaires, anthropometry, biochemical profile and sex hormones were collected at baseline and after 12 weeks of intervention. RESULTS: Women exhibiting a decrease in the markers of DNA damage: tail intensity (24.35 ± 5.86 - pre diet vs. 17.15 ± 5.04 - post-diet; p < 0.001) and tail moment (20.47 ± 7.85 - pre diet vs. 14.13 ± 6.29 - post-diet; p < 0.002). Reduction of calorie intake, weight loss, decreased sexual hormone and cardiometabolic markers such as insulin, homeostasis model assessment of insulin resistance and low-density lipoprotein cholesterol were verified In the multivariate regression analysis, quantitative insulin sensitivity check index and progesterone were responsible for the variation markers in DNA damage before the diet, losing its influence upon diet. CONCLUSION: DNA damage and the impact of cardiometabolic risk factors decreased after the intervention in women with PCOS, indicating the relevance of a nutritional approach in this group of patients.

Effect of Himatanthus sucuuba in Maternal Reproductive Outcome and Fetal Anomaly Frequency in Rats.

The aim of this study was to evaluate the effect of Himatanthus sucuuba on the maternal reproductive outcome and fetal anomaly incidence in rats. Pregnant rats were randomly divided into three experimental groups as follows: Control = treated with water (vehicle), treated 250 = treated with H. sucuuba at dose 250 mg/kg, and treated 500 = treated with H. sucuuba at dose 500 mg/kg. The rats were orally treated, by gavage, with H. sucuuba or vehicle (water) during preimplantation and organogenic period (from gestational day 0-14). At day 21 of pregnancy, all rats were killed to obtain maternal-fetal data. The treatment with H. sucuuba at dose of 250 mg/kg caused reduction in placental efficiency and an increase preimplantation loss rate and placenta weight compared with the control. The treated 500 group presented a significant decrease in maternal weight gain, maternal weight gain minus gravid uterus weight, fetal weight, and placental efficiency compared with the control. In this group, there was a decrease in body weight at day 20 of pregnancy and metacarpus ossification and an increase in the preimplantation loss rate and skeletal anomalies compared with other groups. Himatanthus sucuuba extract caused intrauterine growth restriction, preimplantation loss, and developmental delay in the high doses tested.

Short and long-term repercussions of the experimental diabetes in embryofetal development.

BACKGROUND: Diabetic pregnancy have increased rates of congenital malformation and neonatal mortality. In vitro studies suggest hyperglycemia associated with diabetes impair embryogenesis but in vivo investigations on maternal hyperglycemic insult and early embryo development are scarce. We evaluated the embryofetal development on experimental diabetes models to assess whether hyperglycemia at preimplantation period impairs the progression of pregnancy. METHODS: Different hyperglycemic intensities were obtained by two experimental diabetes models. Female Sprague Dawley rats received streptozotocin at birth (mild diabetes) or at day 90 of life (severe diabetes). For both diabetic groups hyperglycemia was confirmed 5 days after diabetes induction and the mating was performed around 100 day of life. For preimplantation analysis, embryos were recovered at D4 of pregnancy. Another group of animals was submitted to laparotomy at D21 to assess contents of the uterus and fetal viability. RESULTS: Mild (i) and Severe (ii) diabetes modified the early development. Degenerating embryos percentage was higher compared to control (11%) (i) 30.7%, (ii) 37.3%. Cell number mean dropped according to hyperglycemic intensity (control 30.57, (i) 21.42, (ii) 13.42). Pre and post-implantation loss rates were higher in diabetic groups. The fetal viability also decreased from 96% in the control group to (i) 78.7% and (ii) 80.6%. CONCLUSION: Our results show that during diabetic pregnancy, preimplantation embryos present decreased cell number due to higher apoptosis rates, which are dependent of the hyperglycemic intensity. Moreover, fetal viability was also decreased suggesting that the quality of these embryos at long-term may be questioned.

Urethral striated muscle and extracellular matrix morphological characteristics among mildly diabetic pregnant rats: translational approach.

INTRODUCTION AND HYPOTHESIS: Diabetes mellitus (DM) during pregnancy is associated with high levels of urinary incontinence (UI) and pelvic floor muscle dysfunction. Mild DM can lead to changes in urethral striated muscle and extracellular matrix (ECM) in pregnant rats considering both structures as an entire system responsible for urinary continence. METHODS: Ninety-two female Wistar rats were distributed in four experimental groups: virgin, pregnant, diabetic, and diabetic pregnant. In adult life, parental nondiabetic female rats were mated with nondiabetic male rats to obtain newborns. At the first day of birth, newborns received citrate buffer (nondiabetic group) or streptozotocin 100 mg/kg body weight, subcutaneous route (mild DM group). At day 21 of the pregnancy, the rats were lethally anesthetized and the urethra and vagina were extracted as a unit. Urethral and vaginal sections were cut and analyzed by: (a) cytochemical staining for ECM and muscle structural components, (b) immunohistochemistry to identify fast- and slow-muscle fibers, and (c) transmission electron microscopy for ultrastructural analysis of urethral striated muscle. RESULTS: In comparison with the three control groups, variations in the urethral striated muscle and ECM from diabetic pregnant rats were observed including thinning, atrophy, fibrosis, increased area of blood vessels, mitochondria accumulation, increased lipid droplets, glycogen granules associated with colocalization of fast and slow fibers, and a steady decrease in the proportion of fast to slow fibers. CONCLUSIONS: Mild DM and pregnancy can lead to a time-dependent disorder and tissue remodeling in which the urethral striated muscle and ECM has a fundamental function.

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.

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.

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.

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.

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.

Oxidative status in colostrum and mature breast milk related to gestational age and fetal growth.

INTRODUCTION: The effect of gestational age and fetal growth on the oxidant/antioxidant status of breast milk is poorly understood. OBJECTIVE: To evaluate the oxidative stress biomarkers in colostrum and mature milk according to gestational age and fetal growth. METHOD: A longitudinal study with mothers of premature and term infants, born in a tertiary referral hospital between 2014-2018. Inclusion criteria: postpartum women with a singleton pregnancy, who intended to exclusively breastfeed. Exclusion criteria: maternal diabetes, use of medication, drug addiction, congenital infection or malformation, mastitis, and failure to collect colostrum. Four groups were formed according to gestational age and birth weight (appropriate and small): Preterm small (n = 37), Preterm appropriate (n = 99), Full-term small (n = 65), and Full-term appropriate (control, n = 69). The colostrum samples were collected between 24-72 h and the mature milk was sampled in the 4th week of lactation for malondialdehyde (biomarker for lipid peroxidation) and Glutathione peroxidase, Catalase, and Superoxide dismutase measurements. The data were compared among groups using the Chi-square test or Fisher's exact test, one-way analysis of variance followed by Wald's Distribution test and repeated measures analysis of variance. RESULTS: We found a lower malondialdehyde level in colostrum in preterm groups and term small for gestational age, and the antioxidant enzymes Superoxide dismutase and Catalase activities were higher for preterm compared to term groups. The malondialdehyde levels differed in mature milk samples (Full-term small > Full-term appropriate > Preterm small > Preterm appropriate). The malondialdehyde levels increased during lactation in all groups except Preterm appropriate, and the levels of Catalase decreased in preterm groups. CONCLUSION: The oxidative status in breast milk is influenced by gestational age and fetal growth, which increased antioxidant defense for preterm infants and decreased oxidative stimuli for small for gestational age infants. These findings contribute to encouraging breastfeeding for newborns.

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.

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.

Influence of maternal hyperglycemia on IL-10 and TNF-α production: the relationship with perinatal outcomes.

AIMS: This study was conducted to evaluate maternal and placental concentrations of interleukin 10 (IL-10) and tumor necrosis factor-alpha (TNF-α) in pregnant women with glycemic mean (GM) < or ≥100 mg/dL, as well as correlate IL-10 and TNF-α placental concentrations with perinatal outcomes. METHODS: One hundred eighty-six pregnant women were distributed in groups determined by a GM <100 mg/dL or a GM ≥100 mg/dL. The GM, HbA1c levels, maternal and placental concentrations of IL-10 and TNF-α, and the correlation of placental cytokines with perinatal outcomes were evaluated. RESULTS: In maternal blood, the lowest concentrations of IL-10 (p = 0.0019) and TNF-α (p = 0.0185) were observed in the GM ≥100-mg/dL group. The placentas from GM ≥100 mg/dL group exhibited higher TNF-α concentrations (p = 0.0385). Placental IL-10 directly correlated with hemoglobin (r = 0.63; p = 0.02) and insulin (r = 0.78; p = 0.01) levels in the umbilical cord and with 1-min (r = 0.53; p = 0.0095) and 5-min (r = 0.69; p = 0.0003) Apgar scores. Placental TNF-α displayed a tendency to inversely correlate with fetal weight (r = -0.41; p = 0.05). CONCLUSION: Compared to GM <100 mg/dL, GM ≥100 mg/dL was associated with a reduction in maternal IL-10 and TNF-α concentrations and increased placental TNF-α production. Placental IL-10 production was similar in both groups studied and directly correlated with hemoglobin and umbilical cord insulin levels, as well as with the 1- and 5-min Apgar scores.