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Made available in DSpace on 2022-04-29T08:37:18Z (GMT). No. of bitstreams: 0 Previous issue date: 2021-01-01 Clinical and epidemiological studies show that maternal hyperglycemia can change the programming of offspring leading to transgenerational effects. These changes may be related to environmental factors, such as high-fat diet (HFD) consumption, and contribute to the comorbidity onset at the adulthood of the offspring. The objective of this study was to evaluate the hyperglycemic intrauterine environment, associated or not with an HFD administered from weaning to adult life on the periovarian adipose tissue of rat offspring Maternal diabetes was chemically induced by Streptozotocin. Female offsprings were randomly distributed into four experimental groups (n = 5 animals/group): Female offspring from control or diabetic mothers and fed an HFD or standard diet. HFD was prepared with lard enrichment and given from weaning to adulthood. On day 120 of life, the rats were anesthetized and sacrificed to obtain adipose tissue samples. Then, the hyperglycemic intrauterine environment and HFD fed after weaning caused a higher body weight, total fat, and periovarian fat in adult offspring, which could compromise the future reproductive function of these females. These rats showed higher adiposity index and adipocyte area, contributing to hypertrophied adipose tissue. Therefore, maternal diabetes itself causes intergenerational changes and, in association with the HFD consumption after weaning, exacerbated the changes in the adipose tissue of adult female offspring. Laboratory of Experimental Research on Gynecology and Obstetrics Postgraduate Course on Tocogynecology Botucatu Medical School Sao Paulo State University (Unesp Research Support Office Botucatu Medical School Sao Paulo State University (Unesp Laboratory of System Physiology and Reproductive Toxicology Institute of Biological and Health Sciences Federal University of Mato Grosso (UFMT Laboratory of Experimental Research on Gynecology and Obstetrics Postgraduate Course on Tocogynecology Botucatu Medical School Sao Paulo State University (Unesp Research Support Office Botucatu Medical School Sao Paulo State University (Unesp

Made available in DSpace on 2022-04-28T17:22:59Z (GMT). No. of bitstreams: 0 Previous issue date: 2021-10-20 Fundação de Amparo à Pesquisa do Estado de São Paulo (FAPESP) 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. Summary sentence Summary Sentence The association of maternal diabetes and postweaning HFD causes glucose intolerance due to beta-cell disarrangement and impaired insulin secretion, and immunological changes in adult offspring. SJo Paulo State Univ UNESP, Botucatu Med Sch, Lab Expt Res Gynecol & Obstet, Tocogynecol Postgrad Course, Botucatu, SP, Brazil Fed Univ Mato Grosso UFMT, Inst Biol & Hlth Sci, Lab Syst Physiol & Reprod Toxicol, Barra Do Garcas, MT, Brazil Fed Univ Maranhao UFMA, Dept Physiol Sci, Lab Expt Physiol, Sao Luis, MA, Brazil Univ Estadual Paulista UNESP, Botucatu Med Sch, Res Support Off, Botucatu, SP, Brazil SJo Paulo State Univ UNESP, Botucatu Med Sch, Lab Expt Res Gynecol & Obstet, Tocogynecol Postgrad Course, Botucatu, SP, Brazil Univ Estadual Paulista UNESP, Botucatu Med Sch, Res Support Off, Botucatu, SP, Brazil FAPESP: 2016/25207-5

Made available in DSpace on 2021-06-25T10:56:44Z (GMT). No. of bitstreams: 0 Previous issue date: 2021-01-01 Animal models are widely used for studying diabetes in translational research. However, methods for induction of diabetes are conflicting with regards to their efficacy, reproducibility and cost. A comparison of outcomes between the diabetic models is still unknown, especially full-term pregnancy.To understand the comparison, we analyzed the streptozotocin (STZ)-induced diabetes at three life-different moments during the neonatal period in Sprague–Dawley female rats: at the first (D1), second (D2) and fifth (D5) day of postnatal life. At adulthood (90 days; D90), the animals were submitted to an oral glucose tolerance test (OGTT) for diabetic status confirmation. The diabetic and control rats were mated and sacrificed at full-term pregnancy for different analyses. Group D1 presented a higher mortality percentage after STZ administration than groups D2 and D5. All diabetic groups presented higher blood glucose levels as compared to those of the control group, while group D5 had higher levels of glycemia compared with other groups during OGTT. The diabetic groups showed impaired reproductive outcomes compared with the control group. Group D1 had lower percentages of mated rats and D5 showed a lower percentage of a full-term pregnancy. Besides that, these two groups also showed the highest percentages of inadequate fetal weight. In summary, although all groups fulfill the diagnosis criteria for diabetes in adult life, in our investigation diabetes induced on D5 presents lower costs and higher efficacy and reproducibility for studies involving diabetes-complicated pregnancy. Laboratory of Experimental Research on Gynecology and Obstetrics São Paulo State University (UNESP) DNA Repair Laboratory University of São Paulo (USP) Joslin Diabetes Center Harvard Medical School Department of Physiology Charles University Laboratory of System Physiology and Reproductive Toxicology Federal University of Mato Grosso (UFMT) Laboratory of Experimental Research on Gynecology and Obstetrics São Paulo State University (UNESP)

Made available in DSpace on 2021-06-25T10:50:17Z (GMT). No. of bitstreams: 0 Previous issue date: 2021-01-01 The present study aims to confirm if the moderate-intensity swimming has successful glycemic control and non-toxic oxidative stress levels and to verify the influence on pancreatic adaptations, embryo implantation, and placental efficiency. Female Wistar rats were randomly distributed to obtain mildly diabetic by streptozotocin induction at birth and the non-diabetic females given vehicle. At adulthood, pregnant rats were put at random into sedentary non-diabetic rats (ND); exercise non-diabetic rats (NDEx); sedentary diabetic rats (D); and exercise diabetic rats (DEx). The rats of the groups submitted to moderate intensity carried loads equivalent to 4% of body weight. On day 17 of gestational day, all rats were submitted to oral glucose tolerance test (OGTT). Next day (GD18), the rats were anesthetized and killed to count implantation sites and to collect placentas, blood, and muscle samples for biochemical biomarkers and pancreas for immunohistochemical analysis. The moderate exercise used was not sufficient to stimulate the aerobic pathway but presented positive results on glucose metabolism, lower embryo postimplantation loss, and pancreatic morphology compared with the sedentary diabetic group. However, the DEx group showed muscular damage, decreased antioxidant defense, and lipid peroxidation. Thus, the moderate-intensity exercise reduces glycemic levels during OGTT and causes no damage to non-diabetic rats related to other analyzed parameters in this study. The exercised diabetic rats present better glycemic metabolism in OGTT, islet pancreatic morphology, and embryofetal development. However, it is necessary an adjustment in this exercise intensity to improve the effectiveness of aerobic training for reduction of maternal muscular and lipid membrane damages. Southwest Paulista University Center (Unifsp) Laboratory of System Physiology and Reproductive Toxicology Institute of Biological and Health Sciences Federal University of Mato Grosso (UFMT) Departamento de Biología de la Reproducción Instituto Nacional de Ciencias Médicas y Nutrición Salvador Zubirán Laboratory of Experimental Research on Gynecology and Obstetrics Postgraduate Program on Tocogynecology Botucatu Medical School Paulo State University (UNESP) Laboratory of Experimental Research on Gynecology and Obstetrics Postgraduate Program on Tocogynecology Botucatu Medical School Paulo State University (UNESP)

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.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.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; IThe 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.

Made available in DSpace on 2021-06-25T10:36:25Z (GMT). No. of bitstreams: 0 Previous issue date: 2021-02-01 Background: Exercise is commonly recommended to control hyperglycemia, including during pregnancy. We conducted this study to understand the potential benefits and risks of exercise during pregnancy of women with diabetes. Specifically, we evaluated the effects of swimming on a diabetic rat during pregnancy and assayed maternal-fetal parameters. Methods: Diabetes was induced in the female newborn from Wistar rats by the streptozotocin administration on first postnatal day. At 110 days of life, after confirm mild symptoms of diabetes, the rats were mated and randomly distributed into four experimental groups (minimum of 13 animals/group): Control (C)—nondiabetic animals without swimming; Control and Exercise (CEx)—nondiabetic animals submitted to swimming; Mild Diabetic (MD)—diabetic animals without swimming; Mild Diabetic and Exercise (MDEx)—diabetic animals submitted to swimming. The swimming program was performed from day 7 to 21 of pregnancy. Maternal parameters were evaluated during the pregnancy period. On day 21 of pregnancy, the rats were sacrificed and maternal and fetal parameters analyzed. Results: There are no alterations in body weight, food consumption, water intake, and reproductive outcomes among the groups. The swimming program did not normalize maternal glycemia and other biochemical biomarkers. The diabetes and exercise combination increased organ weight. The fetuses born to these exercising diabetic rats had reduced fetal weight and increased skeletal anomalies (mainly incomplete ossification of sternebra). Conclusion: The intense swimming exercise imposed on female rats during pregnancy impaired maternal metabolic repercussions, contributing to intrauterine growth restriction and fetal skeletal anomalies. Laboratory of General Physiology and Reproductive Toxicology Institute of Biological and Health Sciences University Center of Araguaia Federal University of Mato Grosso (UFMT) Laboratory of Experimental Research on Gynecology and Obstetrics Postgraduate Course on Tocogynecology Botucatu Medical School Univ Estadual Paulista_Unesp Laboratory of Experimental Research on Gynecology and Obstetrics Postgraduate Course on Tocogynecology Botucatu Medical School Univ Estadual Paulista_Unesp

Made available in DSpace on 2020-12-12T02:14:16Z (GMT). No. of bitstreams: 0 Previous issue date: 2020-01-01 The objective of the present study was to evaluate maternal reproductive performance, body weight, and frequency of external and internal anomalies of newborns of Wistar Audiogenic Rat (WAR) females as compared with Wistar rats. The adult WAR and Wistar rats were mated within their respective strains. After confirming the pregnancy, the body weights were weekly evaluated. On day 21 of pregnancy, the female rats were anesthetized and sacrificed to evaluate the maternal reproductive outcomes and biochemical profile, newborn weight, and external and internal anomalies. The WAR strain gained less weight during the pregnancy and presented hyperproteinemia, hypertriglyceridemia, and embryonic losses concerning Wistar rats, suggesting an inadequate intrauterine condition for embryonic development and fetal viability. WAR also presented a higher percentage of newborns classified as small for gestational age related to intrauterine growth restriction, which was confirmed by the lower number of ossification centers. There was a higher percentage of skeletal anomalies compared with fetuses of the Wistar dams, confirming their greater susceptibility during the formation and development of their skeletal system. Thus, the WAR presents physiological alterations compromising the viability of their embryos and fetuses, leading to impaired development of the newborns. Tocogynecology Postgraduate Course Laboratory of Experimental Research on Gynecology and Obstetrics Botucatu Medical School São Paulo State University (UNESP) Laboratory of System Physiology and Reproductive Toxicology Institute of Biological and Health Sciences Federal University of Mato Grosso (UFMT) Faculty of Medicine University Center Unicerrado Neurosciences and Behavioral Sciences Department and Physiology Department Ribeirão Preto School of Medicine University of São Paulo Joslin Diabetes Center Harvard Medical School Departamento de Ginecologia e Obstetrícia Faculdade de Medicina de Botucatu - UNESP, Distrito de Rubião Júnior s/n Tocogynecology Postgraduate Course Laboratory of Experimental Research on Gynecology and Obstetrics Botucatu Medical School São Paulo State University (UNESP) Departamento de Ginecologia e Obstetrícia Faculdade de Medicina de Botucatu - UNESP, Distrito de Rubião Júnior s/n

Context Excessive consumption of high-fat diets has increased in the population over time and is harmful to female fertility. Objective To investigate and discuss the effects of a high-fat diet on ovarian follicles in rodents. Data source A systematic literature search of PubMed, EMBASE, Web of Science, and SCOPUS was carried out. Data Extraction Study characteristics, including study design, population, intervention, outcome, and risk of bias were analyzed. Data Analysis Twenty-two articles were included in a systematic review. Given the availability of studies, a quantitative meta-analysis included 12 studies that were performed for outcomes. There was a decrease in primordial follicles in female rodents that received a high-fat diet compared with the standard diet group. The offspring of mothers exposed to a high-fat diet showed an increased number of cystic follicles and a decreased number of secondary follicles and antral follicles, compared with the control diet group. Therefore, these high-fat diet–induced follicular alterations might impair the fertility of dams and their female newborns. Conclusion The consumption of a high-fat diet causes damage to ovarian follicular development, and this commitment will persist in the next generation. Systematic Review Registration PROSPERO registration no. CRD42019133865.

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

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 β 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.

Made available in DSpace on 2022-04-29T08:32:14Z (GMT). No. of bitstreams: 0 Previous issue date: 2021-08-10 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. Laboratory of System Physiology and Reproductive Toxicology Institute of Biological and Health Sciences Federal University of Mato Grosso Laboratory of Experimental Research on Gynecology and Obstetrics Postgraduate Program on Tocogynecology São Paulo State University Laboratory of Experimental Research on Gynecology and Obstetrics Postgraduate Program on Tocogynecology São Paulo State University

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.

Made available in DSpace on 2022-04-29T08:37:16Z (GMT). No. of bitstreams: 0 Previous issue date: 2021-01-01 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. Laboratory of Experimental Research on Gynecology and Obstetrics Gynecology Postgraduate Course on Tocogynecology Botucatu Medical School São Paulo State University (Unesp), São Paulo State Laboratory of System Physiology and Reproductive Toxicology Institute of Biological and Health Sciences Federal University of Mato Grosso (UFMT), Mato Grosso State School of Rehabilitation Faculty of Medicine Université de Montréal Research Center Institut Universitaire de Gériatrie de Montréal Laboratory of Experimental Research on Gynecology and Obstetrics Gynecology Postgraduate Course on Tocogynecology Botucatu Medical School São Paulo State University (Unesp), São Paulo State

Made available in DSpace on 2021-06-25T10:48:02Z (GMT). No. of bitstreams: 0 Previous issue date: 2020-01-01. Added 1 bitstream(s) on 2021-07-15T14:35:24Z : No. of bitstreams: 1 S0001-37652020000700932.pdf: 295985 bytes, checksum: 047baafb6147a16a795c3f86b32498e6 (MD5) Universidade Estadual Paulista Coordenação de Aperfeiçoamento de Pessoal de Nível Superior (CAPES) Fundação de Amparo à Pesquisa do Estado de São Paulo (FAPESP) Conselho Nacional de Desenvolvimento Científico e Tecnológico (CNPq) This study aimed at evaluating the levels of different maternal exercise intensities on maternal and fetal outcomes. Wistar rats were mated and the pregnant rats were distributed into four experimental groups (n = 13 animals/group): Control (Not exercise group-0% of the anaerobic threshold-AT), mild (20%), moderate (80%), and heavy-exercise intensity (140% of AT). These AT were matched to the load of 0, 1, 4 and 7% of the body weight of the animal related to swimming-induced physical intensity. In pregnancy, biomarkers related to maternal blood gases, oxidative stress, metabolism, and reproductive performance, and outcomes of their offspring were analyzed. The mild and moderate-swimming caused no change on implantation, live fetus numbers and oxidative stress status. However, the rats submitted to mild-exercise presented respiratory alkalosis and the heavy-exercise group showed respiratory acidosis. In addition, fetuses of the heavy-exercise dams were smaller for gestational age and lower serum adiponectin levels compared to those of other groups. In conclusion, the moderate-exercise intensity caused beneficial effects for maternal environment and the mild and moderate-exercise presented similar fetal repercussions. Nevertheless, the heavy-exercise intensity caused maternal metabolic alterations that damaged the fetal growth. Therefore, these findings confirm that physical intensity should be carefully conducted to avoid maternal complications and, consequently, compromised fetal repercussions. Universidade Estadual Paulista/ UNESP Laboratório de Pesquisa Experimental em Ginecologia e Obstetrícia, Distrito de Rubião Jr, s/n Universidade Federal do Mato Grosso/UFMT Instituto de Ciências Biológicas e da Saúde Laboratório de Fisiologia dos Sistemas e Toxicologia Reprodutiva, Av. Valdon Varjão, 6390 Instituto Nacional de Ciências Médicas e Nutrição Salvador Zubirán Departamento de Biologia Reprodutiva, Belisario Domínguez Secc, 16 Universidade Estadual Paulista/ UNESP Laboratório de Pesquisa Experimental em Ginecologia e Obstetrícia, Distrito de Rubião Jr, s/n CAPES: 001 FAPESP: 2012/25168-9 CNPq: 475073/2013-4

Made available in DSpace on 2020-12-12T01:58:56Z (GMT). No. of bitstreams: 0 Previous issue date: 2020-05-23 Conselho Nacional de Desenvolvimento Científico e Tecnológico (CNPq) Ethnopharmacological relevance: Phyllanthus niruri is a well-known plant for its therapeutic purposes to treat various diseases, being widely used by the population, mainly by women. However, there is no scientific confirmation of the effects of use during pregnancy. Aim of the study: Evaluating the effect of Phyllanthus niruri aqueous extract on the maternal toxicity, reproductive outcomes and fetal anomaly incidence in rats. Materials and methods: Pregnant rats were distributed into four experimental groups: Control = treated with water (vehicle); Treated 150 = treated with P. niruri at dose 150 mg/kg and; Treated 300 = treated with P. niruri at dose 300 mg/kg; and Treated 600 = treated with P. niruri at dose 600 mg/kg. The rats were treated by intragastric route (gavage) with P. niruri or vehicle (water) from gestational day 0 to 21. At day 21 of pregnancy, maternal reproductive outcomes, biochemical profile and maternal renal tissue were evaluated. The fetuses and placentas were collected and analyzed. Results: Treatment with P. niruri did not alter the reproductive performance outcomes of rats. However, treated 600 group presented with changes in maternal kidney weight and morphology. The plant did not present teratogenic effect, but caused fetal macrosomia and increased ossification sites. Conclusion: Treatment with aqueous extract of P. niruri administered during gestation did not cause reproductive toxicity, but led to changes in maternal kidneys and in offspring weight, showing that the leaf extract of this plant can produce detrimental effects during pregnancy. Laboratory of System Physiology and Reproductive Toxicology Institute of Biological and Health Sciences Federal University of Mato Grosso Laboratory of Experimental Research on Gynecology and Obstetrics Postgraduate Course on Tocogynecology Univ Estadual Paulista_Unesp Laboratory of Experimental Research on Gynecology and Obstetrics Postgraduate Course on Tocogynecology Univ Estadual Paulista_Unesp

Made available in DSpace on 2020-12-10T20:01:26Z (GMT). No. of bitstreams: 0 Previous issue date: 2020-01-01 Fundacao de Amparo a Pesquisa do Estado de Mato Grosso (FAPEMAT), Cuiaba, Brazil (2014-2016) Background: Limited studies have been canied out with prednisone (PRED) in treatment by glucose intolerant individuals, even in this model the animals presented low blood glucose levels at adulthood, by the high regenerative capacity of beta-cell. Objective: The aim was to evaluate the effects of the treatment of PRED in mild diabetes on biochemical and immunological biomarkers. Methods: Rats were randomly divided into four groups: control (C), treated control C+PRED (treatment of 1.25 mg/Kg/day PRED); diabetic DM (mild diabetes) and treated diabetic DM PRED (treatment with same dose as C+PRED group). Untreated groups received vehicle, adjusted volume to body weight. The treatment lasted 21 days and measured body weight, food and water intake, and glycemia weekly. In the 3rd week, the Oral Glucose Tolerance Test (OGTT) and the Insulin Tolerance Test (ITT) was performed. On the last day, the rats were killed and the blood was collected for biochemical analyzes, leukogram and imm.unoglobulin G levels. Results: There was a significant decrease in body weight in mild diabetes; however, the treatment in diabetic groups increased food intake, glycemia, and the number of total leukocytes, lymphocytes and neutrophils. On the other hand, it decreased the levels of triglycerides, high -density and very low density lipoproteins. In addition, diabetic groups showed glucose intolerance and mild insulin resistance, confirming that this model induces glucose intolerant in adult life. Conclusion: The results showed that the use of prednisone is not recommended for glucose intolerant individuals and should he replaced in order to not to aggravate this condition. Sao Paulo State Univ UNESP, Inst Biosci, Postgrad Program Pharmacol & Biotechnol, Botucatu, SP, Brazil Univ Sao Paulo, Fac Med Ribeirao Preto, Dept Physiol, Sao Paulo, Brazil Fed Univ Mato Grosso UFMT, Inst Biol Sci & Hlth, Lab Syst Physiol & Reprod Toxicol, Barra Do Garcas, Mato Grosso, Brazil Sao Paulo State Univ UNESP, Inst Biosci, Postgrad Program Pharmacol & Biotechnol, Botucatu, SP, Brazil Fundacao de Amparo a Pesquisa do Estado de Mato Grosso (FAPEMAT), Cuiaba, Brazil (2014-2016): 002 - 004/2015 Fundacao de Amparo a Pesquisa do Estado de Mato Grosso (FAPEMAT), Cuiaba, Brazil (2014-2016): 36016.541.21414.17082016

Made available in DSpace on 2021-06-25T10:44:03Z (GMT). No. of bitstreams: 0 Previous issue date: 2020-11-01 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. Laboratory of Experimental Research on Gynecology and Obstetrics Postgrad. Course on Tocogynecology Botucatu Med. Sch. S. Paulo State Univ. (Unesp) Botucatu S. Paulo State Laboratory of Experimental Research on Gynecology and Obstetrics Postgrad. Course on Tocogynecology Botucatu Med. Sch. S. Paulo State Univ. (Unesp) Botucatu S. Paulo State

Made available in DSpace on 2019-10-06T16:02:14Z (GMT). No. of bitstreams: 0 Previous issue date: 2018-12-01 Coordenação de Aperfeiçoamento de Pessoal de Nível Superior (CAPES) Fundação de Amparo à Pesquisa do Estado de São Paulo (FAPESP) 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-β 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-β 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. Laboratory of Experimental Research on Gynecology and Obstetrics Gynecology Obstetrics and Mastology Post Graduate Course Botucatu Medical School Univ Estadual Paulista_Unesp DeVry Ruy Barbosa School (DeVry Brazil Group) Laboratory of System Physiology and Reproductive Toxicology Institute of Biological and Health Sciences Federal University of Mato Grosso (UFMT) Department of Morphology Botucatu Bioscience Institute Univ Estadual Paulista_Unesp Biomedical Research Centre Universidad de Valparaíso Laboratory of Experimental Research on Gynecology and Obstetrics Gynecology Obstetrics and Mastology Post Graduate Course Botucatu Medical School Univ Estadual Paulista_Unesp Department of Morphology Botucatu Bioscience Institute Univ Estadual Paulista_Unesp FAPESP: 2011/18519-7

Made available in DSpace on 2018-12-11T17:22:23Z (GMT). No. of bitstreams: 0 Previous issue date: 2018-11-01 Coordenação de Aperfeiçoamento de Pessoal de Nível Superior (CAPES) Background: Fetal impairment caused by a deleterious intrauterine environment may have long-term consequences, such as oxidative stress and genetic damage. Rats born as small-for-gestational-age (SPA) were submitted to exercise (swimming) before and during pregnancy. The animals exhibited glucose intolerance, reduced general adiposity, and increased maternal and offspring organ weight, showing the benefit of exercise for these rats. We hypothesised that regular exercise in SPA during gestation could prevent DNA damage in these animals and in their offspring, contributing to altered fetal programming of metabolism in the offspring. Severe diabetes was induced by streptozotocin treatment, to obtain SPA newborns. At adulthood, pregnant SPA rats were randomly distributed into two groups: exercised (SPAex – submitted to swimming program) or not-exercised (SPA – sedentary rats). Post-partum, blood was collected for analysis of DNA damage (comet assay) and oxidative stress. SPAex rats presented lower DNA damage levels, decreased lipid peroxidation, and a lower rate of newborns classified as large-for-pregnancy-age. DNA damage was also lower in SPAex newborns. We conclude that swimming applied to SPA pregnant rats contributes to decreased DNA damage and lipid peroxidation in the dams, and decreased DNA damage and macrosomia in their offspring. Postgraduate Course on Gynecology Obstetrics and Mastology Laboratory of Experimental Research on Gynecology and Obstetrics Botucatu Medical School São Paulo State University - UNESP Biochemical Department Havana Medical Science University ICBP Victoria de Girón Laboratory of System Physiology and Reproductive Toxicology Institute of Biological and Health Sciences Federal University of Mato Grosso (UFMT) Mato Grosso State Department of Anesthesiology Botucatu Medical School São Paulo State University - UNESP Postgraduate Course on Gynecology Obstetrics and Mastology Laboratory of Experimental Research on Gynecology and Obstetrics Botucatu Medical School São Paulo State University - UNESP Department of Anesthesiology Botucatu Medical School São Paulo State University - UNESP

Moderate hyperglycaemic levels seem to be related to abnormal gastric motility in diabetes mellitus. However, experimental models designed to evaluate the relationship between motility and diabetes over time are not yet well established. Our objective was to investigate the long‐term effects of mild diabetes on gastric motility in rats. Newborn male rats received streptozotocin (mild diabetes groups – MD) or vehicle (control groups – C), and both groups were evaluated after 3 (C3 and MD3) and 6 months (C6 and MD6) postinduction. Mild diabetic animals (MD3 and MD6) showed moderately elevated blood glucose and decreased insulin levels compared with control (C3 and C6). Insulin secretion was enhanced in MD6 compared with MD3, most likely due to partial β‐cell regeneration indicated by HOMA‐β. In HOMA‐IR, it was noticed that MD6 animals had impaired insulin response compared with MD3. Gastric emptying was faster, amplitude of contraction was stronger in MD6 compared with MD3, and in both groups, the differences were significant when compared with control animals. A significant abnormal rhythmic index was calculated for the mild diabetic groups, despite unchanged mean frequency of contraction. In conclusion, despite increased insulin levels over time, constant levels of moderate hyperglycaemia are also related to abnormal gastric motility and impairment of gastric function.

Made available in DSpace on 2018-12-11T17:16:45Z (GMT). No. of bitstreams: 0 Previous issue date: 2018-01-02 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. Laboratory of System Physiology and Reproductive Toxicology Institute of Biological and Health Sciences Federal University of Mato Grosso (UFMT) Gynecology Obstetrics and Mastology Graduate Course Laboratory of Experimental Research on Gynecology and Obstetrics Botucatu Medical School Univ Estadual Paulista_Unesp Gynecology Obstetrics and Mastology Graduate Course Laboratory of Experimental Research on Gynecology and Obstetrics Botucatu Medical School Univ Estadual Paulista_Unesp

Made available in DSpace on 2018-12-11T17:16:53Z (GMT). No. of bitstreams: 0 Previous issue date: 2017-10-01. Added 1 bitstream(s) on 2019-10-09T18:31:25Z : No. of bitstreams: 1 S0001-37652017000602749.pdf: 1125780 bytes, checksum: 0bf2528284f0ca40742afec84cbe102c (MD5) Fundação de Amparo à Pesquisa do Estado de São Paulo (FAPESP) Conselho Nacional de Desenvolvimento Científico e Tecnológico (CNPq) Several studies present different methodologies and results about intensity exercise, and many of them are performed in male rats. However, the impact of different type, intensity, frequency and duration of exercise on female rats needs more investigation. From the analysis of blood lactate concentration during lactate minimum test (LacMin) in the swimming exercise, the anaerobic threshold (AT) was identified, which parameter is defined as the transition point between aerobic and anaerobic metabolism. LacMin test is considered a good indicator of aerobic conditioning and has been used in prescription of training in different exercise modalities. However, there is no evidence of LacMin test in female rats. The objective was to determine AT in non-pregnant and pregnant Wistar rats. The LacMin test was performed and AT defined for mild exercise intensity was from a load equivalent to 1% of body weight (bw), moderate exercise as carrying 4% bw and severe intensity as carrying 7% bw. In pregnant rats, the AT was reached at a lower loading from 5.0% to 5.5% bw, while in non-pregnant the load was from 5.5% to 6.0% bw. Thus, this study was effective to identify exercise intensities in pregnant and non-pregnant rats using anaerobic threshold by LacMin test. Laboratório de Pesquisa Experimental de Ginecologia e Obstetrícia Faculdade de Medicina de Botucatu Universidade Estadual Paulista/UNESP, Distrito de Rubião Jr, s/n Laboratório de Fisiologia de Sistemas e Toxicologia Reprodutiva Instituto de Ciências Biológicas e da Saúde Universidade Federal de Mato Grosso/UFMT, Av. Valdon Varjão, 6390 Laboratório de Pesquisa Experimental de Ginecologia e Obstetrícia Faculdade de Medicina de Botucatu Universidade Estadual Paulista/UNESP, Distrito de Rubião Jr, s/n FAPESP: 2012/25168-9 CNPq: 475073/2013-4

Made available in DSpace on 2018-12-11T17:11:19Z (GMT). No. of bitstreams: 0 Previous issue date: 2017-01-01. Added 1 bitstream(s) on 2019-10-09T18:30:59Z : No. of bitstreams: 1 S0001-37652017000100263.pdf: 1427292 bytes, checksum: ef8ec5b644aa193fcbff3e9d83e32cc3 (MD5) Bauhinia holophylla, commonly known as “cow’s hoof”, is widely used in Brazilian folk medicine for the diabetes treatment. Therefore, the aim of this study was at evaluating the aqueous extract effect of Bauhinia holophylla leaves treatment on the streptozotocin-induced diabetic rats. Diabetes was induced by Streptozotocin (40 mg/Kg) in female Wistar rats. Oral administration of aqueous extract of Bauhinia holophylla leaves was given to non-diabetic and diabetic rats at a dose of 400 mg/kg during 21 days. On day 17 of treatment, the Oral Glucose Tolerance Test was performed to determine the area under the curve. At the end of the treatment, the animals were anesthetized and blood was collected for serum biochemical parameters analysis. After treatment with Bauhinia holophylla extract, non-diabetic and diabetic rats presented no glycemic changes. On the other hand, the plant treatment decreased body weight and increased ALT and AST activities. In conclusion, the treatment with aqueous extract of B. holophylla leaves given to diabetic rats presented no hypoglycemic effect in nondiabetic animals and no antidiabetic effect in diabetic animals with the doses studied. In addition, the diabetic animals treated with the B. holophylla extract showed inconvenient effects and its indiscriminate consumption requires particular carefulness. Laboratório de Fisiologia de Sistemas e Toxicologia Reprodutiva Instituto de Ciências Biológicas e da Saúde Universidade Federal de Mato Grosso/ UFMT, Av. Valdon Varjão, 6390 Laboratório de Pesquisa Experimental de Ginecologia e Obstetrícia Faculdade de Medicina de Botucatu Universidade Estadual Paulista/ UNESP Distrito de Rubião Jr s/n Laboratório de Pesquisa Experimental de Ginecologia e Obstetrícia Faculdade de Medicina de Botucatu Universidade Estadual Paulista/ UNESP Distrito de Rubião Jr s/n

Made available in DSpace on 2019-10-06T16:25:39Z (GMT). No. of bitstreams: 0 Previous issue date: 2019-06-01 Coordenação de Aperfeiçoamento de Pessoal de Nível Superior (CAPES) Fundação de Amparo à Pesquisa do Estado de São Paulo (FAPESP) 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 (β)-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. Laboratory of Experimental Research of Gynecology and Obstetrics Postgraduate Course of Gynecology Obstetrics and Mastology Botucatu Medical School São Paulo State University (UNESP) DeVry Ruy Barbosa School (DeVry Brazil Group) Department of Pathology National Institute of Medical Sciences and Nutrition “Salvador Zubirán” Department of Pathology School of Veterinary Medicine and Animal Science (FMVZ) São Paulo State University (UNESP) Laboratory of System Physiology and Reproductive Toxicology Institute of Biological and Health Sciences Federal University of Mato Grosso (UFMT) Laboratory of Experimental Research of Gynecology and Obstetrics Postgraduate Course of Gynecology Obstetrics and Mastology Botucatu Medical School São Paulo State University (UNESP) Department of Pathology School of Veterinary Medicine and Animal Science (FMVZ) São Paulo State University (UNESP) FAPESP: 2011/18519-7

Made available in DSpace on 2019-10-06T16:18:07Z (GMT). No. of bitstreams: 0 Previous issue date: 2019-01-01. Added 1 bitstream(s) on 2021-07-15T14:35:45Z : No. of bitstreams: 1 S0001-37652019000100702.pdf: 7025300 bytes, checksum: 9f180013f38351c25bebb93a28efba4e (MD5) Coordenação de Aperfeiçoamento de Pessoal de Nível Superior (CAPES) Universidade Estadual Paulista Fructose consumption has increased worldwide, and it has been associated with the development of metabolic diseases such as insulin resistance (IR) and steatosis. The aim was to evaluate if lower fructose concentrations may cause pancreatic structural abnormalities, leading to a glucose intolerance without steatosis in male rats. Young male rats orally received 7% fructose solution for 12 weeks. Body weight, food, water, and energy intake were measured. An oral glucose tolerance test (OGTT) was performed. After final experimental period, all rats were anaesthetized and killed. Blood samples were collected for biochemical analyses and organs (liver and pancreas) were processed for morphological analyses. Fructose consumption was not associated with lipid accumulation in liver. However, fructose administration was associated with an increased area under curve from OGTT and an increased percentage of insulin-positive cells, high beta cell mass and reduced pancreatic islet area. Fructose supplementation (7%) did not cause steatosis, but it led to abnormal morphology and function of pancreatic islet cells, contributing for glucose intolerance development. Our findings demonstrate that even low fructose concentrations may cause deleterious effects in animals. Laboratório de Fisiologia de Sistemas e Toxicologia Reprodutiva Instituto de Ciências Biológicas e da Saúde Universidade Federal de Mato Grosso/UFMT Avenida Valdon Varjão Laboratório de Pesquisa Experimental de Ginecologia e Obstetrícia Faculdade de Medicina de Botucatu Universidade Estadual Paulista/UNESP, Distrito de Rubião Junior, s/n Laboratório de Pesquisa Experimental de Ginecologia e Obstetrícia Faculdade de Medicina de Botucatu Universidade Estadual Paulista/UNESP, Distrito de Rubião Junior, s/n CAPES: 001

Made available in DSpace on 2019-10-06T16:13:55Z (GMT). No. of bitstreams: 0 Previous issue date: 2018-01-01 The diabetic syndrome affects pregnancy, contributing to placental functional and structural disruptions and impaired fetal development, with many reports indicating tobacco-associated morbidity and perinatal mortality. In our study, an experimental rat model of diabetes and cigarette smoke exposure in pregnant rats was used to determine the impact of the combination of diabetes and exposure to cigarette smoke during pregnancy on maternal oxidative stress biomarkers and placental and fetal development. Diabetes was induced by streptozotocin, and dams were exposed to cigarette smoke by mainstream smoke generated by a mechanical smoking device and delivered into a chamber. Four groups of dams were studied: nondiabetic (C, control) and diabetic (D) exposed to filtered air and nondiabetic (CS) and diabetic (DS) exposed to cigarette smoke prior to and during pregnancy. Maternal oxidative stress biomarkers, placental morphology, and fetal growth were determined close to term. The combination of diabetes and cigarette smoke resulted in elevated maternal blood glucose levels and increased number of small fetuses. Placentas from the DS group showed increased junctional zone and decreased labyrinthine area. The morphological alterations were characterized by extensive vascular congestion, thickness, and hyalinization of the vascular walls, numerous decidual cells with abundant glycogen, and macrophages with cytoplasmic inclusions of hemosiderin. Additionally, they showed increased glycogen accumulation and junctional zone structural derangement with ectopic giant cells. No alterations were observed in maternal oxidative stress status. Thus, our result suggests that diabetes makes pregnant rats more susceptible to the adverse effects of exposure to cigarette smoke on placental morphometry and fetal growth. Laboratory of Experimental Research on Gynecology and Obstetrics Botucatu Medical School Sao Paulo State University (UNESP) Department of Cell and Developmental Biology Institute of Biomedical Sciences University of São Paulo (USP) Laboratory of System Physiology and Reproductive Toxicology Institute of Biological and Health Sciences Federal University of Mato Grosso (UFMT) Experimental Pathology Section Department of Pathology National Institute of Medical Sciences and Nutrition Laboratory of Experimental Research on Gynecology and Obstetrics Botucatu Medical School Sao Paulo State University (UNESP)

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 β-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.

Hyperglycemia increases glycosylation with O-linked N-acetyl-glucosamine (O-GlcNAc) contributing to placental dysfunction and fetal growth impairment. Our aim was to determine how O-GlcNAc levels are affected by hyperglycemia and the O-GlcNAc distribution in different placental regions.Female Wistar rats were divided into the following groups: severe hyperglycemia (300 mg/dL; n = 5); mild hyperglycemia (140 mg/dL, at least than two time points during oral glucose tolerance test; n = 7) or normoglycemia (120 mg/dL; n = 6). At 21 days of pregnancy, placental tissue was collected and processed for morphometry and immunohistochemistry analyses, or properly stored at -80 °C for protein quantification by western blot.Placental index was increased only in severe hyperglycemic rats. Morphometric analysis showed increased junctional zone and decreased labyrinth region in placentas exclusively from the severe hyperglycemic group. Proteins targeted by O-GlcNAc were detected in all regions, with increased O-GlcNAc levels in the hyperglycemic group compared to control and mild hyperglycemic rats. Proteins in endothelial and trophoblast cells were the main target for O-GlcNAc. Whereas no changes in O-GlcNAc transferase (OGT) expression were detected, O-GlcNAcase (OGA) expression was reduced in placentas from the severe hyperglycemic group and augmented in placentas from the mild hyperglycemic group, compared with their respective control groups.Placental O-GlcNAc overexpression may contribute to placental dysfunction, as indicated by the placental index. Additionally, morphometric alterations, occurring simultaneously with increased O-GlcNAc accumulation in the placental tissue may contribute to placental dysfunction during hyperglycemia.