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Query: UMLS:C0011849 (diabetes)
 277,896 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Placentae from control and diabetic patients were used to test three null hypothesis: (1) there are no significant group differences in the volumes of villous syncytiotrophoblast compartments or intervillous fibrin-type fibrinoid, (2) perivillous fibrin-type fibrinoid is deposited randomly at the surface of trophoblast, and (3) amounts and deposition patterns of perivillous fibrin-type fibrinoid do not vary between groups. Term placentae were collected from non-diabetic subjects and five groups of diabetic women classified according to duration, severity and insulin dependence. Tissue specimens and sections were obtained by uniform random sampling. Volumes and surface areas of fibrin-type fibrinoid and trophoblast compartments (thin, syncytial knot, syncytial bridge and denuded regions) were estimated stereologically and compared using variance, chi-squared and contingency table analyses. As to null hypothesis (1), no group differences in volumes of trophoblast compartments were found but volumes of intervillous fibrin-type fibrinoid were greater in the non-insulin-dependent diabetic group. As to null hypothesis (2), regardless of group, fibrin-type fibrinoid was deposited preferentially at sites of denudation in every placenta examined. As to null hypothesis (3), villous surface areas occupied by perivillous fibrin-type fibrinoid were greater in type 1 (insulin-dependent) diabetics with complications (diabetic nephropathy or retinopathy). The surfaces of trophoblast occupied by fibrin-type fibrinoid were also notably larger in non-insulin-dependent diabetics and type 1 diabetics with complications. Except for the surface of denudation sites (which also increased in diabetes), there were no differences in the surfaces of trophoblast regions. These results confirm that the haemostatic steady state is perturbed in the diabetic placenta, that perivillous fibrin-type fibrinoid is deposited preferentially at sites of epithelial loss/damage, and that some diabetic groups are affected differentially.
Placenta 2003 May
PMID:Maternal diabetes mellitus is associated with altered deposition of fibrin-type fibrinoid at the villous surface in term placentae. 1274 29

Recent research suggests a significant role for placental corticotropin-releasing hormone (CRH) in controlling human parturition. This paper describes the expression of CRH, CRH receptors 1 and 2, and CRH binding protein (CRH-BP) in gestational tissue in late pregnancy. Placenta, myometrium, decidua, and fetal membranes were collected after uncomplicated pregnancies at term caesarian section before the onset of labour. The localisation and mRNA expression of CRH, CRH receptors, and CRH-BP were studied by immunohistochemistry and reverse transcription (RT)-PCR. CRH receptors were detected in placenta, myometrium, decidua, and fetal membranes. We demonstrated for the first time the presence of CRH receptors on resident macrophages and on endothelial cells. CRH receptor 1 mRNA was detected in all tissues investigated by RT-PCR, whereas CRH receptor 2 mRNA was restricted to myometrium and decidua. CRH mRNA was widely expressed in all tissue under study. Novel findings are also presented on the expression of CRH-BP in the myometrium. This widespread expression of the CRH system in gestational tissue suggests a paracrine role for CRH in the birth process (e.g. effects on macrophages and endothelial cells).
Exp Clin Endocrinol Diabetes 2003 May
PMID:Expression patterns of CRH, CRH receptors, and CRH binding protein in human gestational tissue at term. 1278 89

Unexplained intra-uterine fetal death is still a problem in diabetic pregnancies, especially in those with an LGA-infant. We hypothesized that in these pregnancies impaired placental function, in terms of abnormal placental weight and/or abnormal placental histology, may account for this phenomenon. To test this hypothesis, we assessed the relative placental weight and scored several histological abnormalities in 34 AGA- and 24 LGA-placentae of type 1 diabetic women and in 22 AGA- and 16 LGA-placentae of control women. Relative placental weight was comparable in the LGA-diabetic cases and in the control groups, but was significantly higher in the AGA-diabetic subgroup. Histological abnormalities such as the presence of nucleated fetal red blood cells, fibrinoid necrosis, villous immaturity and chorangiosis were observed more often in the diabetic placentae compared with the control placentae. These differences in histology were particularly observed when we compared both AGA-groups. LGA-control placentae showed a high incidence of histological abnormalities, almost comparable to the diabetic placentae. Only fibrinoid necrosis was significantly more common in the LGA-diabetic placentae. Three of the four cases of perinatal death/asphyxia in the diabetic group concerned an LGA-infant with a relative low placental weight. In conclusion, placentae of women with type 1 diabetes showed several abnormalities that can be associated with impaired functioning. The difference between AGA- and LGA-diabetic placentae was related to relative placental weight and our data suggest that an increase in relative weight may protect the fetus from asphyxia. Placentae from LGA-non-diabetic women showed several similarities to those of women with diabetes.
Placenta
PMID:Placental pathology in women with type 1 diabetes and in a control group with normal and large-for-gestational-age infants. 1312 78

Fetal development is dependent on maternal supply of fuels and building blocks. Disturbed maternal metabolism or inappropriate maternal nutrition confronts the fetus with an unfavourable intra-uterine milieu. Structural and functional adaptations occur during development and maturation of organs. Consequences of these fetal alterations persist postnatally and may result in metabolic alterations throughout life. Gestational diabetes can occur in these offspring and transmit the effect to the next generation. These alterations in fetal development can be associated with fetal macrosomia (maternal diabetes) or fetal growth-restriction (maternal/fetal malnutrition). The relation between birth weight and later metabolic disease therefore is U-shaped. Adult metabolic condition is thus to a considerable extent programmed in utero, fetal and neonatal weight being symptoms of disturbed fetal development. This concept of intra-uterine programming of disease is illustrated with a review of epidemiological human studies and experimental animal studies.
Placenta 2003 Nov
PMID:Intra-uterine transmission of disease. 1458 Mar 72

Endothelium-derived nitric oxide (NO) plays a key role in the regulation of vascular tone in health and disease. The present study addresses the contribution of NO to the baseline vascular tone in the fetal placental circulation of type 1 diabetic women. To this end, we performed ex-vivo dual perfusions of isolated cotyledons from seven women with type 1 diabetes mellitus and 24 healthy women. The fetal arterial pressure was considered to be a measure of fetal vascular resistance. The contribution of NO to the baseline vascular tone of the fetal placental circulation was quantified by addition of the NO-synthase inhibitor N(G)-nitro-arginine-methylester (L-NAME). Apart from the diabetic state, we studied the influence of exogenous insulin on the response to L-NAME. Mean (+/-SEM) baseline fetal arterial pressure was higher in diabetes (25.7+/-3.4 mm Hg vs 18.0+/-1.7 mm Hg, P<0.05). Maximum perfusion pressure after L-NAME was 87.9+/-7.1 mm Hg in diabetes vs 58.9+/-4.5 mm Hg in controls (P<0.01). The net L-NAME-induced increase in fetal arterial pressure was higher in diabetes (62.2+/-9.1 mm Hg vs 40.9+/-3.5 mm Hg, P<0.05). Although insulin induced a shift to the left of the L-NAME-curve, the net L-NAME-induced increase in fetal arterial pressure was not affected. We conclude that diabetes is associated with an increased baseline vascular tone of the fetal placental vascular bed. This can not be explained by attenuated NO-mediated effects. In contrast, the activity of the NO-pathway seems to be increased in diabetes. The latter observation seems not to be caused by high insulin levels.
Placenta 2003 Nov
PMID:Nitric oxide-mediated vascular tone in the fetal placental circulation of patients with type 1 diabetes mellitus. 1458 Mar 80

Matrix metalloproteinases (MMPs) are involved in placental remodelling throughout pregnancy. Diabetes mellitus induces alterations in tissue production of NO, a regulator of MMPs activity. The present work evaluates placental and fetal MMPs and NO levels during midpregnancy in neonatal streptozotocin-induced diabetic rats. MMP-2 and MMP-9 immunolabelling was increased both in the labyrinth zone (p<0.001) and in the giant trophoblast cells of the junctional zone (p<0.001) from diabetic placenta, when compared with controls. Also MMP-2 (p<0.01) and MMP-9 (p<0.005) activities were increased in both maternal and fetal sides of diabetic placenta when related to controls. In both sides of the diabetic placenta, nitrate/nitrite concentrations (which indicate NO production) were higher than in controls (p<0.05). An intense immunostaining for nitrotyrosine, indicating peroxynitrite-induced damage, was found in both labyrinth (p<0.001) and junctional zones (p<0.001) of diabetic placenta. Enhanced MMP-2 activity (p<0.05) and NO production were also higher in the fetuses from diabetic rats when compared to controls (p<0.005). These findings demonstrate alterations in MMPs and NO in the feto-placental unit of diabetic rats, anomalies that are likely to be involved in the developmental alterations induced by maternal diabetes.
Placenta 2005 Apr
PMID:Increased matrix metalloproteinases 2 and 9 in placenta of diabetic rats at midgestation. 1582 20

Insulin-dependent diabetes mellitus (Type I) is associated with disregulation of the glucose and oxygen metabolic pathways during pregnancy, both of which affect placental villous development. Term complete placentas and placental bed biopsies, between 37 and 40 weeks, from 12 singleton pregnancies complicated by Type I diabetes were collected following delivery by elective Caesarean section. The controls consisted of 10 term placentas from uncomplicated pregnancies delivered by elective Caesarean section. Villous morphology was investigated using unbiased histomorphometric techniques, in relation to the degree of transformation of the spiral arteries and the presence of fetal macrosomia. A significant increase in fetal and placental weights, placental volume, volumes of the intervillous space and the trophoblast was found in the diabetic group compared to the controls. A significant reduction in the villous membrane specific diffusing capacity was observed between the diabetic and control groups (1.32 vs 1.72 cm3 min(-1)mmHg(-1)kg(-1), P=0.032). A significant increase in the volume of the intermediate and terminal villi, the surface area of the villi and of the fetal capillaries, and the harmonic thickness of the villous membrane was found in the macrosomic subgroup compared to the controls. There were no differences between the hypertensive subgroup with histological evidence of partial transformation of the spiral arteries and the controls. These data indicate that placental development in insulin-dependent diabetic pregnancies is affected differentially when pregnancies complicated by fetal macrosomia are separated from those complicated by maternal hypertensive disorders with partial transformation of the spiral arteries. The reduction in the specific diffusing capacity of the villous membrane may contribute to the fetal hypoxia and increased fetal and neonatal morbidity associated with diabetes.
Placenta
PMID:Villous histomorphometry and placental bed biopsy investigation in Type I diabetic pregnancies. 1600 23

The aims of the present study were to evaluate the umbilical cord serum activin A concentrations in complicated pregnancies and also to explore the relationship between activin A levels and blood flow velocity in fetal arteries. Umbilical cord blood samples were obtained postpartum after a full term uneventful gestation (control group, n=40), and from pregnancies complicated by gestational diabetes (n=13), preterm labour (n=18), or pre-eclampsia (n=19). Cord serum activin A levels were three-fold higher in pregnancies complicated by pre-eclampsia (1.17+/-0.14 ng/ml, p<0.01) than in the control group (0.43+/-0.03 ng/ml), but were unaltered in the diabetes and preterm labour groups. The pre-eclampsia group had a marked increase of umbilical artery pulsatility index (PI) and also a decrease of middle cerebral artery PI (p<0.01). Furthermore, activin A concentration correlated directly with the umbilical artery PI (r=0.540, p=0.021), with the length of stay in the Neonatal Intensive Care Unit (r=0.857, p<0.001) and also with cord blood pH (r=-0.886, p<0.001). In conclusion, umbilical cord serum activin A levels are increased in the presence of pre-eclampsia and provide an indirect marker of impaired blood flow in the uteroplacental and fetal circulation.
Placenta
PMID:Umbilical cord serum activin A levels are increased in pre-eclampsia with impaired blood flow in the uteroplacental and fetal circulation. 1605 48

Preeclampsia and diabetes are complications of pregnancy that contribute to maternal and perinatal mortality worldwide. Results emerging from molecular studies of placentae may elucidate etiologically important genomic alterations. Appropriate application of real time reverse transcription (RT) PCR in comparative gene expression studies requires endogenous housekeeping genes to normalize between sample variations. Ideal housekeeping genes must have stable tissue expression, but few have been specifically studied in the placenta. We sought to identify candidate control genes by analyzing seven functionally distinct housekeeping genes (B2M, GAPDH, HMBS, HPRT, SDHA, TBP, YWHAZ) for their expression stability and level in the placenta. mRNA isolated from 20 placentae was analyzed for gene expression using RT-PCR. Expression stability (M) was assessed using normalization strategies previously used for other tissues. TBP and SDHA were the most stable, with an average expression stability of M = 0.43, followed by YWHAZ (M = 0.44) > HPRT (M = 0.53) > HMBS (M = 0.57) > GAPDH (M = 0.61) > B2M (M = 0.69). The genes tested ranged in abundance, with an approximately 300-fold increase from the lowest (HMBS) to the highest (B2M). By using TBP, SDHA and YWHAZ, with greater expression stability than those housekeeping genes commonly used in placenta studies, gene expression profile comparisons will have more sensitivity and specificity.
Placenta
PMID:Evaluation of housekeeping genes in placental comparative expression studies. 1608 39

Throughout its entire lifespan, the placenta is able to produce as well as respond to a variety of inflammatory stimuli. Many signaling molecules and concurrent pathways responsible for the propagation of an inflammatory response have been identified in placental cells. From early developmental stages onward, the secretory activity of placenta cells clearly contributes to increase local as well as systemic levels of cytokines and inflammatory molecules. Two aspects of the progression of an immune response have been particularly investigated: the highly regulated process of invasion and implantation and, the induction of preterm labor associated with infections. With the progression of pregnancy, the physiological role of most placental cytokines is more uncertain. Many placental cytokines are similar to adipose tissue derived cytokines. One possibility is that they contribute to the low grade systemic inflammation developing during the third trimester of pregnancy. The prevalent hypothesis is that activation of some inflammatory pathways is necessary to induce maternal insulin resistance which is required for the progression of normal gestation. As an integrative organ, the placenta may relay or enhance the contribution made by the cells of the adipose tissue and immune system in non-pregnant individuals. In pregnancy complicated with obesity or diabetes mellitus, continuous adverse stimulus is associated with dysregulation of metabolic, vascular and inflammatory pathways supported by increased circulating concentration of inflammatory molecules. It is believed that maternal adipose tissue and placental cells both contribute to the inflammatory situation by releasing common molecules. For example, the accumulation of leptin and TNF-alpha is associated with an increased production for markers of inflammation, fibrotic response, vascular remodeling and proteins facilitating lipid storage within the placenta.
Placenta 2006 Aug
PMID:The placenta cytokine network and inflammatory signals. 1624 70


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