Effects of Maternal Diabetes and Diet on Gene Expression in the Murine Placenta

Adverse exposures during pregnancy have been shown to contribute to susceptibility for chronic diseases in offspring. Maternal diabetes during pregnancy is associated with higher risk of pregnancy complications, structural birth defects, and cardiometabolic health impairments later in life. We showed previously in a mouse model that the placenta is smaller in diabetic pregnancies, with reduced size of the junctional zone and labyrinth. In addition, cell migration is impaired, resulting in ectopic accumulation of spongiotrophoblasts within the labyrinth. The present study had the goal to identify the mechanisms underlying the growth defects and trophoblast migration abnormalities. Based upon gene expression assays of 47 candidate genes, we were able to attribute the reduced growth of diabetic placenta to alterations in the Insulin growth factor and Serotonin signaling pathways, and provide evidence for Prostaglandin signaling deficiencies as the possible cause for abnormal trophoblast migration. Furthermore, our results reinforce the notion that the exposure to maternal diabetes has particularly pronounced effects on gene expression at midgestation time points. An implication of these findings is that mechanisms underlying developmental programming act early in pregnancy, during placenta morphogenesis, and before the conceptus switches from histiotrophic to hemotrophic nutrition.

A Study on Morphohistometric Changes of Placenta in Gestational Diabetes- A Comparative Analysis

Introduction:The placenta is a complex fetal organ that fulfills pleotrophic roles during fetal growth. Placenta is the most accurate record of the infant’s prenatal experience. Gestational diabetes is much common than preexisting diabetes .i.e. it complicates 2% to 5% of pregnancies. It seems reasonable to expect that biochemical changes occurring in the pregnant women with diabetes should be reflected in the placental structure. Aim & objectives: In the present study an attempt is made to know the morphological changes of placenta in gestational diabetes mellitus.Subjects and Methods:In this study totally 60 placentae were studied, of which 30 were nondiabetic placentae and 30 from Gestational Diabetic mothers were studied macroscopically. Morphologically the shape, site of attachment of umbilical cord, central thickness of placenta was noted. Birth weight of the neonate and the placental ratio were also recorded. By using routine staining techniques and direct microscopy tissues of Gestational Diabetic placenta were studied qualitatively and compared them with normal placenta.Results:Our study demonstrates that there is a significant increase in weight and central thickness of placenta. Neonatal weight and placental ratio were also increased; there was no change in shape and site of attachment of umbilical cord in case of diabetic placenta when compared to normal. Conclusion:On the basis of results of present study it is concluded that diabetic placentae showed increase in weight and central thickness. Neonatal weight and placental ratio were also increased. These findings indicate that control of hyperglycemia only partially prevents the development of placental abnormalities.

Glucose, Insulin, and Oxygen Interplay in Placental Hypervascularisation in Diabetes Mellitus

The placental vasculature rapidly expands during the course of pregnancy in order to sustain the growing needs of the fetus. Angiogenesis and vascular growth are stimulated and regulated by a variety of growth factors expressed in the placenta or present in the fetal circulation. Like in tumors, hypoxia is a major regulator of angiogenesis because of its ability to stimulate expression of various proangiogenic factors. Chronic fetal hypoxia is often found in pregnancies complicated by maternal diabetes as a result of fetal hyperglycaemia and hyperinsulinemia. Both are associated with altered levels of hormones, growth factors, and proinflammatory cytokines, which may act in a proangiogenic manner and, hence, affect placental angiogenesis and vascular development. Indeed, the placenta in diabetes is characterized by hypervascularisation, demonstrating high placental plasticity in response to diabetic metabolic derangements. This review describes the major regulators of placental angiogenesis and how the diabetic environmentin uteroalters their expression. In the light of hypervascularized diabetic placenta, the focus was placed on proangiogenic factors.

Fractalkine (CX3CL1) and Its Receptor CX3CR1 May Contribute to Increased Angiogenesis in Diabetic Placenta

Chemokine CX3CL1 is unique, possessing the ability to act as a dual agent: chemoattractant and adhesive compound. Acting via its sole receptor CX3CR1, CX3CL1 participates in many processes in human placental tissue, including inflammation and angiogenesis. Strongly upregulated by hypoxia and/or inflammation-induced inflammatory cytokines secretion, CX3CL1 may act locally as a key angiogenic factor. Both clinical observations and histopathological studies of the diabetic placenta have confirmed an increased incidence of hypoxia and inflammatory reactions with defective angiogenesis. In this study we examined comparatively (diabetes class C complicated versus normal pregnancy) the correlation between CX3CL1 content in placental tissue, the mean CX3CR1 expression, and density of the network of placental microvessels. A sandwich enzyme immunoassay was applied for CX3CL1 measurement in placental tissue homogenates, whereas quantitative immunohistochemical techniques were used for the assessment of CX3CR1 expression and the microvascular density. Significant differences have been observed for all analyzed parameters between the groups. The mean concentration of CX3CL1 in diabetes was increased and accompanied by augmented placental microvessel density as well as a higher expression of CX3CR1. In conclusion, we suggest involvement of CX3CL1/CX3CR1 signaling pathway in the pathomechanism of placental microvasculature remodeling in diabetes class C.