Marlúcia Bastos Aires

Effects of maternal diabetes on trophoblast cells.

Diabetes mellitus (DM) is a health condition characterized by hyperglycemia over a prolonged period. There are three main types of DM: DM type 1 (DM1), DM2 and gestational DM (GDM). Maternal diabetes, which includes the occurrence of DM1 and DM2 during pregnancy or GDM, increases the occurrence of gesttional complications and adverse fetal outcomes. The hyperglycemic intrauterine environment affects not only the fetus but also the placental development and function in humans and experimental rodents. The underlying mechanisms are still unclear, but some evidence indicates alterations in trophoblast proliferation, apoptosis and cell cycle control in diabetes. A proper coordination of trophoblast proliferation, differentiation and invasion is required for placental development. Initially, increased expression of proliferative markers in junctional and labyrinth zones of rat placentas and villous cytotrophoblast, syncytiotrophoblast, stromal cells and fetal endothelial cells in human placentas is reported among diabetics. Moreover, reduced apoptotic index and expression of some apoptotic genes are described in placentas of GDM women. In addition, cell cycle regulators including cyclins and cyclin-dependent kinase inhibitors seem to be affected by the hyperglycemic environment. More studies are necessary to check the balance between proliferation, apoptosis and differentiation in trophoblast cells during maternal diabetes.

Maternal diabetes affects rat placental morphology and pregnancy

Diabetes mellitus (DM) is a worldwide public health problem and is increasing because of the high prevalence of obesity and sedentarism. Diabetes during pregnancy may be divided into clinical diabetes (in cases previously diagnosed with type 1 or type 2 diabetes) and gestational diabetes (GD) [1]. In the Brazilian health public system, 7.6 % of pregnant women older than 20 years are diabetic [2]. Results from human and rodent diabetic experimental models have suggested that the placenta is a compromised target, which largely suffers the impact of maternal diabetes. This causes problems in maternal and fetal exchange, which increases abnormal fetal development and perinatal morbidity rates. Stereology is a well-established method for generating absolute three-dimensional quantities, such as volume, surface area, and length of complex tissues from twodimensional histological sections [3]. Stereological studies on human and animal pregnancies have shown that fetal growth is accompanied by changes in functional morphology of the placenta [4, 5]. No stereological studies have been conducted on the placenta of alloxan diabetic rats. This would be a useful tool for studying placental development in an animal model for diabetes and may provide valuable information regarding the physiopathology of maternal diabetes in humans. In view of the importance of diabetes during pregnancy for maternal and neonatal health, the objective of the present study was to assess placental and fetal weight, and placental morphological changes in diabetic female rats using histological and stereological techniques.

Rat visceral yolk sac cells: viability and expression of cell markers during maternal diabetes

The function of the visceral yolk sac (VYS) is critical for embryo organogenesis until final fetal development in rats, and can be affected by conditions such as diabetes. In view of the importance of diabetes during pregnancy for maternal and neonatal health, the objective of this study was to assess fetal weight, VYS cell markers, and viability in female Wistar rats (200-250 g) with induced diabetes (alloxan, 37 mg/kg) on the 8th gestational day (gd 8). At gd 15, rats from control (n=5) and diabetic (n=5) groups were anesthetized and laparotomized to remove the uterine horns for weighing of fetuses and collecting the VYS. Flow cytometry was used for characterizing VYS cells, and for determining mitochondrial activity, cell proliferation, DNA ploidy, cell cycle phases, and caspase-3 activity. Fetal weight was reduced in the diabetic group. Expression of the cell markers CD34, VEGFR1, CD115, CD117, CD14, CCR2, CD90, CD44, STRO-1, OCT3/4, and Nanog was detected in VYS cells in both groups. In the diabetic group, significantly decreased expression of CD34 (P<0.05), CCR2 (P<0.001), and OCT3/4 (P<0.01), and significantly increased expression of CD90 (P<0.05), CD117 (P<0.01), and CD14 (P<0.05) were observed. VYS cells with inactive mitochondria, activated caspase-3, and low proliferation were present in the rats with diabetes. Severe hyperglycemia caused by maternal diabetes had negative effects on pregnancy, VYS cell viability, and the expression of cell markers.

Diabetes consequences in the fetus liver of the non-obese diabetic mice

DM type 1 (T1D) incidence is increasing around 3% every year and represents risks for maternal and fetal health. The objective of this study was to explore the effects of diabetes on fetus liver cells in non-obese diabetic (NOD) mice. Hyperglycemic NOD (HNOD), normoglycemic NOD (NNOD) and BALB/c females were used for mating, and the fetus livers were collected at 19.5 gestation day (gd). HNOD group had reduced fetal weight (989.5±68.32 vs 1290±57.39 mg BALB/c, P<0.05) at 19.5 gd and higher glycemia (516.66±28.86 mg dl−1, P<0.001) at both 0.5 gd and 19.5 gd compared to other groups. The protein expression of albumin (ALB) was significantly reduced in HNOD group (0.9±0.2 vs 3.36±0.36 NNOD P<0.01, vs 14.1±0.49 BALB/c P<0.001). Reduced gene expression of ALB (1.34±0.12 vs 5.53±0.89 NNOD and 5.23±0.71 BALB/c, P<0.05), Hepatic Nuclear Factor-4 alpha (HNF-4α) (0.69±0.1 vs 3.66±0.36 NNOD, P<0.05) and miR-122 (0.27±0,10 vs 0.88±0.15 NNOD, P<0.05) was present in HNOD group. No difference for alpha-Fetoprotein (AFP) and gene expression was observed. In conclusion, our findings show the impacts of T1D on the expression of ALB, AFP, HNF-4α and miR-122 in fetus liver cells by using NNOD and HNOD mice.

Morphological alterations in the heart and aorta of rats treated with glucocorticoids

Introduction: The objective of this study was to analyze the morphological structure of the heart and aorta of rats treated with the synthetic glucocorticoid dexamethasone. Material and Methods: Male Wistar rats were divided into two groups: 08 control rats undergoing treatment with a 0.9% saline solution for 10 days and 08 rats treated for 10 days with dexamethasone (2mg/kg animal weight). Results: Histological analysis detected a mild cardiac hypertrophy and 15% reduction of collagen located in the aorta of animals treated with glucocorticoid when compared to the control group. Conclusion: We conclude that treatment with dexamethasone for a period of 10 consecutive days is able to promote morphological changes in the structure of the heart chamber and, impair morphological structure of aorta.