Diabetic Placenta Research Articles

Identification of Mucopolysaccharide Types in Diabetic Placenta and Umbilical Cord Tissues

Identification of Mucopolysaccharide Types in Diabetic Placenta and Umbilical Cord Tissues

The interplay of inflammation and placenta in maternal diabetes: insights into Hofbauer cell expression patterns.

Inflammation of the placenta is harmful to both the fetus and the mother. Inflammation is strongly associated with diabetes, a common complication of pregnancy. Hofbauer cells (HBCs), unique immune system cells of fetal origin in the placenta, play complex roles, including growth of placental villi and their branching, stromal remodelling, and angiogenesis. Our study investigated the expression of IL-1β, IL-10, CYP2C8, CYP2C9, CYP2J2 and sEH in HBCs from patients with type 1 diabetes mellitus (T1DM) and gestational diabetes mellitus (GDM) compared to healthy controls using immunohistochemistry. We also assessed the structure of the villus stroma using Masson´s trichrome. In T1DM, HBCs showed inflammatory activation characterised by increased IL-1β and decreased CYP epoxygenase expression compared to normal placentas. Conversely, significant inflammation in HBCs appeared less likely in GDM, as levels of IL-1β and CYP epoxygenases remained stable compared to normal placentas. However, GDM showed a significant increase in sEH expression. Both types of diabetes showed delayed placental villous maturation and hypovascularisation, with GDM showing a more pronounced effect. The expression profiles of IL-1β, CYP epoxygenases and sEH significantlly differ between controls and diabetic placentas and between T1DM and GDM. These facts suggest an association of the CYP epoxygenase-EETs-sEH axis with IL-1β expression as well as villous stromal hypovascularisation. Given the stable high expression of IL-10 in both controls and both types of diabetes, it appears that immune tolerance is maintained in HBCs.

Placental weight percentile curves in a Danish population.

The role of the placenta is to transport oxygen and nutrients to the fetus, and a well-functioning placenta is vital to fetal health. Our aim was to develop placental weight percentile curves adjusted by gestational age, and stratified by major maternal comorbidities. The study was a population study in a Danish cohort. Data was drawn from The Medical Birth Register and the National Patient Register. We included singleton births with a gestational age of 22 + 0 to 42 + 6 weeks. We excluded multiple pregnancies, stillbirths and retained placentas. A total of 611 418 placentas were included. Percentile line graphs were created in groups of all placentas, hypertensive disorders and diabetic disorders. Tables and figures are presented for placental weight percentile curves according to gestational age for all placentas, hypertensive disorders and diabetic disorders, respectively. Placental weight was generally higher in the diabetic placentas, and lower in the hypertensive placentas. These percentile curves may serve as a reference for other populations, and may be useful for other studies investigating the role of the placenta in relation to pregnancy outcomes, and health in later life.

Comparative study of microvascular structural changes in the gestational diabetic placenta.

Microvascular morphology and pathological changes in gestational diabetes mellitus (GDM) placentas and normal placentas were observed via vascular casting technology, electron microscopy, and pathological detection technology. Vascular structure and histological morphology changes in GDM placentas were examined to generate basic experimental data for the diagnosis and prognostic determination of GDM. This case-control study involving 60 placentas, 30 from healthy controls and 30 from patients with GDM. Differences in size, weight, volume, umbilical cord diameter, and gestational age were assessed. Histological changes in the placentas in the two groups were analyzed and compared. A placental vessel casting model was constructed using a self-setting dental powder technique, to compare the two groups. The placental cast microvessels of the two groups were compared using scanning electron microscopy. There were no significant differences in maternal age or gestational age between the GDM group and the control group (p > .05). The size, weight, volume, and thickness of the placentas in the GDM group were significantly greater than those in the control group, as was umbilical cord diameter (p < .05). Immature villus, fibrinoid necrosis, calcification, and vascular thrombosis were significantly greater in the placental mass in the GDM group (p < .05). The terminal branches of the microvessels in diabetic placenta casts were sparse, with significantly fewer ends and lower villous volume (p < .05). Gestational diabetes can cause gross and histological changes in the placenta, particularly placental microvascular changes.

Distinct Changes in Placental Ceramide Metabolism Characterize Type 1 and 2 Diabetic Pregnancies with Fetal Macrosomia or Preeclampsia.

Disturbances of lipid metabolism are typical in diabetes. Our objective was to characterize and compare placental sphingolipid metabolism in type 1 (T1D) and 2 (T2D) diabetic pregnancies and in non-diabetic controls. Placental samples from T1D, T2D, and control pregnancies were processed for sphingolipid analysis using tandem mass spectrometry. Western blotting, enzyme activity, and immunofluorescence analyses were used to study sphingolipid regulatory enzymes. Placental ceramide levels were lower in T1D and T2D compared to controls, which was associated with an upregulation of the ceramide degrading enzyme acid ceramidase (ASAH1). Increased placental ceramide content was found in T1D complicated by preeclampsia. Similarly, elevated ceramides were observed in T1D and T2D pregnancies with poor glycemic control. The protein levels and activity of sphingosine kinases (SPHK) that produce sphingoid-1-phosphates (S1P) were highest in T2D. Furthermore, SPHK levels were upregulated in T1D and T2D pregnancies with fetal macrosomia. In vitro experiments using trophoblastic JEG3 cells demonstrated increased SPHK expression and activity following glucose and insulin treatments. Specific changes in the placental sphingolipidome characterize T1D and T2D placentae depending on the type of diabetes and feto-maternal complications. Increased exposure to insulin and glucose is a plausible contributor to the upregulation of the SPHK-S1P-axis in diabetic placentae.

The impact of hyperglycemia upon BeWo trophoblast cell metabolic function: A multi-OMICS and functional metabolic analysis.

Pre-existing and gestationally-developed diabetes mellitus have been linked with impairments in placental villous trophoblast cell metabolic function, that are thought to underlie the development of metabolic diseases early in the lives of the exposed offspring. Previous research using placental cell lines and ex vivo trophoblast preparations have highlighted hyperglycemia is an important independent regulator of placental function. However, it is poorly understood if hyperglycemia directly influences aspects of placental metabolic function, including nutrient storage and mitochondrial respiration, that are altered in term diabetic placentae. The current study examined metabolic and mitochondrial function as well as nutrient storage in both undifferentiated cytotrophoblast and differentiated syncytiotrophoblast BeWo cells cultured under hyperglycemia conditions (25 mM glucose) for 72 hours to further characterize the direct impacts of placental hyperglycemic exposure. Hyperglycemic-exposed BeWo trophoblasts displayed increased glycogen and triglyceride nutrient stores, but real-time functional readouts of metabolic enzyme activity and mitochondrial respiratory activity were not altered. However, specific investigation into mitochondrial dynamics highlighted increased expression of markers associated with mitochondrial fission that could indicate high glucose-exposed trophoblasts are transitioning towards mitochondrial dysfunction. To further characterize the impacts of independent hyperglycemia, the current study subsequently utilized a multi-omics approach and evaluated the transcriptomic and metabolomic signatures of BeWo cytotrophoblasts. BeWo cytotrophoblasts exposed to hyperglycemia displayed increased mRNA expression of ACSL1, HSD11B2, RPS6KA5, and LAP3 and reduced mRNA expression of CYP2F1, and HK2, concomitant with increased levels of: lactate, malonate, and riboflavin metabolites. These changes highlighted important underlying alterations to glucose, glutathione, fatty acid, and glucocorticoid metabolism in BeWo trophoblasts exposed to hyperglycemia. Overall, these results demonstrate that hyperglycemia is an important independent regulator of key areas of placental metabolism, nutrient storage, and mitochondrial function, and these data continue to expand our knowledge on mechanisms governing the development of placental dysfunction.

The impact of maternal diabetes on birth to placental weight ratio and umbilical cord oxygen values with implications for fetal-placental development

IntroductionWe determined the impact of gestational diabetes (GDM) and pre-existing diabetes (DM) on birth/placental weight and cord oxygen values with implications for placental efficiency and fetal-placental growth and development. MethodsA hospital database was used to obtain birth/placental weight, cord PO2 and other information on patients delivering between Jan 1, 1990 and Jun 15, 2011 with GA >34 weeks (N = 69,854). Oxygen saturation was calculated from the cord PO2 and pH data, while fetal O2 extraction was calculated from the oxygen saturation data. The effect of diabetic status on birth/placental weight and cord oxygen values was examined adjusting for covariates. ResultsBirth/placental weights were stepwise decreased in GDM and DM compared to non-diabetics with placentas disproportionally larger indicating decreasing placental efficiency. Umbilical vein oxygen was marginally increased in GDM but decreased in DM attributed to the previously reported hyper-vascularization in diabetic placentas with absorbing surface area of capillaries initially increased, but then constrained by increasing distance from maternal blood within the intervillous space. Umbilical artery oxygen was unchanged in GDM and DM, with fetal O2 extraction decreased in DM indicating that fetal O2 delivery must be increased relative to O2 consumption and likely due to increased umbilical blood flow. DiscussionIncreased villous density/hyper-vascularization in GDM and DM with placentas disproportionately larger and umbilical blood flow increased, are postulated to normalize umbilical artery oxygen despite increased birth weights and growth-related O2 consumption. These findings have implications for mechanisms signaling fetal-placental growth and development in diabetic pregnancies and differ from that reported with maternal obesity.

Microscopic Manifestations of Maternal Diabetes in Placental Structure

The human placenta is crucial for prenatal development and good pregnancy outcome. Maternal diabetic disorder influences normal intrauterine development of individual and expresses itself in the placenta. Due to the progress in diagnostic methods and methods of metabolic compensation the macroscopic signs associated with maternal diabetes, e.g., placentomegaly, occur nowadays rarely. In the microscopic picture of placenta there are no structural differences specific for maternal diabetes. However, the application of quantitative morphological methods has revealed some differences of normal and diabetic placenta. Stereological studies have shown significantly higher total volume of peripheral villi that distorts shapes and dimensions of pores in the intervillous space, and larger surface areas of peripheral villi and villous capillaries. Methods of confocal microscopy and 3D reconstruction gave the evidence that the fetus reacts on the hypoxia in maternal diabetic environment by enhanced angiogenesis and branching of villous capillaries. The enhanced tissue volumes are conditioned by higher mitotic activity. However, it decreases the proliferative potential of cells taking part in the enlargement of key structures for maternofetal transport at the end of pregnancy. Syncytiotrophoblast produces many factors playing important roles in maternal and fetal regulation and in the placenta itself. Quantitative methods of catalytic histochemistry and immunocytochemistry pointed at the role of maternal diabetes in decreased synthesis of some of those factors (e.g., alkaline phosphatase, SP1 glycoprotein). The presented data show that the quantitative morphological methods contribute to better understanding of the influence of maternal diabetes on fetoplacental unit.

Metabolism of the mother, placenta and fetus in diabetes

Metabolic changes occur due to the effects of placental hormones such as human chorionic gonadotropin and human placental lactogen in normal pregnancies. These effects enable the development of insulin resistance among all pregnant women, significantly pronounced in the third trimester. In pregnancies complicated by pre-gestational or gestational diabetes mellitus, these changes are more intensive as they affect the fetoplacental unit. In pregnancies complicated by diabetes the increased number of placental macrophages leads to the increased production of different cytokines which include leptin, tumor necrosis factor alpha, and interleukins. This review addresses placental vascular changes that lead to adverse pregnancy outcomes, along with the effects of the maternal hyperglycemia and fetal hyperinsulinemia.

EFFECTS OF METFORMIN AND INSULIN ON MORPHOLOGY, STEREOLOGY AND MEAN MORPHOMETRIC DIFFUSION CAPACITY IN DIABETIC PLACENTA

Background: Insulin given for the treatment of GDM is associated with hypoxic changes whereas Metformin has beneficial micro-vascular effects on the placenta. This comparative drug study was conducted with objectives to compare the effects of Metformin and Insulin on the morphology and stereology in gestational diabetes. And to calculate and compare the mean morphometric diffusion capacity for oxygen in Metformin and Insulin treated gestational diabetics. Methods: This clinical trial was conducted from Jan 2018 to Feb 2019 in the Department of Pharmacology, Basic Medical Sciences Institute, in collaboration with the Department of Obstetrics and Gynaecology, Jinnah Postgraduate Medical Centre, Karachi. Out of 136 high-risk females, 83 confirmed gestational diabetics were enrolled in second trimester and were further randomised into Group A (oral Metformin therapy) and Group B (subcutaneous Insulin therapy). They were followed till term and after delivery. Collected placentae (35 in each group) were subjected to gross, microscopic and detailed stereological study. Results: Placental weight on gross, hypoxic changes such as immature villi, chorangiosis and syncytial knots on light microscopic morphology, placental volume, the total volume of placental villi and total volume of foetal connective tissue on stereology were significantly more in Insulin-treated diabetic placentae whereas the mean villi diameter and mean morphometric diffusion capacity was significantly more in Metformin-treated placentae. Conclusion: Metformin-treated placentae were significantly different as compared to the insulin-treated placenta. Metformin treated placentae showed better morphometric diffusion capacity for oxygen than insulin treated placentae. Pak J Physiol 2022;18(2):22?7

Pregnancy complications and risk of uterine rupture among women with singleton pregnancies in China

BackgroundThe goal of this study was to investigate whether pregnancy complications are associated with an increased risk of uterine rupture (UR) and how that risk changes with gestational age.MethodsWe obtained all data from China’s National Maternal Near Miss Surveillance System (NMNMSS) between 2012 and 2018. Poisson regression analysis was used to assess the risk of UR with pregnancy complications (preeclampsia, gestational diabetes mellitus, placental abruption, placenta previa and placenta percreta) among 9,454,239 pregnant women. Furthermore, we analysed the risks of UR with pregnancy complications in different gestational age groups.ResultsThe risk of UR was increased 2.0-fold (1.2-fold to 2.7-fold) in women with pregnancy complications (except for preeclampsia). These associations also persisted in women without a previous caesarean delivery. Moreover, an increased risk of UR before term birth was observed among women with gestational diabetes mellitus, placental abruption and placenta percreta. The risk of UR was slightly higher in women with gestational diabetes mellitus who had a large for gestational age (LGA) foetus, especially at 32 to 36 weeks gestation.ConclusionsThe risk of UR is associated with gestational diabetes mellitus, placental abruption, placenta previa and placenta percreta, but varies in different gestational ages.

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.

Immunolocalization of FOXP3, JAK1 and STAT5 in Preeclamptic, Intrauterine Growth Restricted and Gestational Diabetic Human Placentas

Objective: The aim of the study to show the relation of T cells in placental villous fragments with FOXP3,JAK1 and STAT5 receptors in different conditions such as GDM, PE and IUGR placental tissues. Methods: Specimens of ten(10) diabetic placentas, ten(10) preeclamptic, ten(10) intrauterine growth restricted placentas and ten(10) control placentas were collected by systematic uniform random sampling. Immunohistochemical detections of FOXP3, JAK1 and STAT5 were performed in histological sections for each group’s placental tissue. The H-score value was derived for each specimen by calculating the sum of the percentage of syncytiotrophoblast and syncytial nodes in placenta and intervillus area. They were categorized by intensity of staining, multiplied by its respective score. Results: FOXP3, JAK1 and STAT5 immunoreactivity comparisons are shown in four groups of placentas. FOXP3 immunoreactions significantly increase in GDM group. JAK1 and STAT5 immunoreactions significantly decrease in PE group. STAT5 immunoreactivity was detected crucially increase in GDM group. Discussion: The results showed that in different conditions such as PE,GDM and IUGR, T cells in placental villous fragments have relation with FOXP3,JAK1 and STAT5 receptors and that FOXP3 can inactivate the PE and IUGR in the placental tissue. We have also confirmed as other studies that JAK-STAT pathway plays important role in PE,IUGR and GDM placental tissue.

Histochemical Study of Human Placental Tissues in Gestational Diabetic Mellitus

Gestational diabetes mellitus (GDM) is a serious pregnancy complication in which a woman who has never had diabetes develops chronic hyperglycemia during her pregnancy. Normal placental function is essential for optimal fetal growth. The transport of glucose from the mother to the fetus is critical for fetal nutrient demands and can be stored as glycogen in the placenta. However, the function of this glycogen deposition is unknown: It may well be a source of fuel for a placenta itself or the storage reservoir for the later use by the fetus in times of need. While the significance of the placental glycogen remains unknown, the mounting evidence indicates that the altered glycogen metabolism and/or deposition is associated with many pregnancy complications, such as gestational diabetes, that adversely affect fetal development. The aim of this study is to assess glycogen deposition using Histochemical staining of Periodic Acid Schiff (PAS) stain. The placenta tissue collected from 50 women were enrolled in this study (25 women with no complications) and (25 women with gestational diabetes). The placentas of the two groups were compared in this study based on glycogen deposition with periodic acid-Schiff stain. The results of a histochemical investigation using PAS stain revealed a significant increase in the glycogen deposition (p≤0.001) in diabetic women's placentas within the intervillous core, around fetal vessels, and the basement membranes.

Role of EBAF/Nodal/p27 signaling pathway in development of placenta in normal and diabetic rats

Placentas control the maternal–fetal transport of nutrients and gases. Placental reactions to adverse intrauterine conditions affect fetal development. Such adverse conditions occur in pregnancies complicated by diabetes, leading to alterations in placental anatomy and physiology. In this study, streptozocin (STZ) injection produced sustained hyperglycemia during pregnancy in rats. Hyperglycemic pregnant rats had gained significantly less weight than normal pregnant rats on embryonic day 15.5. We investigated the influence of diabetes on placental anatomy and physiology. Compared with controls, the diabetic group had a markedly thicker junctional zone at embryonic day 15.5. To explore a mechanism for this abnormality, we examined Nodal expression in the junctional zone of control and diabetic groups. We found lower expression of Nodal in the diabetic group. We then investigated the expression of its target gene p27Kip1 (p27), which is related to cell proliferation. In vitro, Nodal overexpression up-regulated p27 protein levels while interfered EBAF up-regulated p27. In vivo, the expression of p27 was lower in diabetic compared with normal rats, and localization was similar between the two groups. In contrast, a higher expression of PCNA was found in diabetic versus normal placenta. Endometrial bleeding associated factor (EBAF), an up-stream molecular regulator of Nodal, was expressed at higher levels in placenta from diabetic versus normal rats. Based on these results, we speculate that the EBAF/Nodal/p27 signaling pathway plays a role in morphological change of diabetic placenta.

Advanced Maternal Age and Pregnancy Outcome at Manipal Teaching Hospital: Cross-sectional Analytical study

Introduction: Advanced and very advanced maternal age are associated with several adverse maternal and fetal outcome. The objective of this study was to find out the possible association between advance maternal age and adverse pregnancy outcomes at Manipal Teaching Hospital.Methods: A cross sectional analytical study conducted at department of Obstetrics and Gynecology, Manipal Teaching Hospital, Pokhara, Nepal. A total of 198 patient who were ≥30 years and &gt;24 weeks pregnant admitted in obstetric ward were selected. These patient were divided into three groups according to their age (30-34, 35-39 and ≥ 40years). We compared the incidence of adverse maternal and perinatal outcome among these groups. We also calculated odds ratio of maternal and perinatal outcomes in 35-39 years and ≥ 40years women, compared with women aged 30-34 years.Results: Comparison of the three age groups revealed that advanced maternal age constitute a predisposing factor for malpresentation, gestational diabetes mellitus, placenta previa, fetal distress and caesarean section. Whereas, risk of non progress of labour, preterm birth, postpartum hemorrhage, perinatal death and congenital anomalies were increased in very advanced maternal age group. From these, statistical significance was reached in case of greater risk of malpresentation (p=0.01,OR=6.66), fetal distress (p=0.04, OR=2.6) and caesarean section(p=0.02,OR=2.06) in advanced age group when compared to the patients aged 30-34. Furthermore, very advanced age group were higher risk of postpartum hemorrhage (p=0.03, OR=2.47) and congenital anomalies, which were statistically significant (p=0.04, OR=29.57) when compared to the 30-34 years.Conclusion: Advanced and very advanced maternal age is associated with several adverse maternal and perinatal outcome. The risk of perinatal complication begin to increase after the age of 35 but significantly increased after 40 years.

The effect of adiponectin and its receptors in placental development of diabetic rats

Placenta development is an essential process for normal fetal growth and development, and healthy pregnancy maintenance. Inadequate placental development may cause clinical complications like diabetes, intrauterine growth retardation and preeclampsia. Due to limited data about placental expression of adiponectin, which has anti-diabetic effects, we studied the relationship between adiponectin and placental development in streptozotocin (STZ)-induced diabetic and normal rats. We also investigated Adiponectin receptors and the downstream adiponectin molecules like peroxisome proliferator-activated receptor (PPAR) α, PPARγ, retinoic acid receptor (RXR)α in the development of the diabetic placenta to explain the effects of Adiponectin in detail. Diabetic rat placentas were found to be heavier than control placentas at the 18th and 20th gestational days, while diabetic embryos were lighter than control group at the 14th, 18th and 20th days of gestation. Adiponectin protein level decreased in diabetic placenta towards term. Moreover, maternal serum adiponectin levels were found to be significantly decreased in diabetic group. Adiponectin receptor 1 (AdipoR1) mRNA expression levels were similar between groups, while Adiponectin receptor 2 (AdipoR2) mRNA expression was significantly decreased at the 14th, 18th and 20th days of gestation in diabetic placentas. Additionally, the mRNA and protein expression of PPARα, PPARγ, and RXRα were found to be decreased in diabetic placentas. These observations show that diabetes and pregnancy is associated with adiponectin levels. In conclusion, our data reveals that adiponectin plays a role in improvement of placental development in diabetic conditions, in the investigated animal species.

288 Assessing in vivo placental function in pregnancies complicated by maternal diabetes mellitus

We sought to examine fetal brain and placental response to maternal hyperoxia using blood oxygen level–dependent (BOLD) magnetic resonance imaging (MRI) in pregnancies complicated by diabetes mellitus (DM). This is a single center prospective case control cohort study of women with singleton gestations, at least 18 weeks or greater. Cases include women diagnosed with either pre-gestational or gestational DM. Controls include healthy pregnancies without any comorbidities. Gradient-echo planar and fast spin-echo T2 weighted imaging was performed with a maternal hyperoxia paradigm of 2 minutes resting state baseline (RS), 6 minutes maternal hyperoxia (HO) of 100% oxygen via a non-rebreather and 5.6 minutes post oxygenation for return to resting state (RR). Analyses were performed at one minute time intervals to assess the change in R2* from baseline (ΔR2*). Student’s t-test was performed to compare outcomes between groups. Of the 113 women recruited, 67 (59.3%) healthy controls with mean gestational age (GA) in weeks 30.9 ± 4.3, and 46 (40.7%) cases, mean GA 30.2 ± 4.5. Of the cases 13 (28.26%) had Type 1 DM, 15 (32.61%) were diagnosed with Type 2 DM, 17 (36.96%) had Gestational (G) DM and 1 (2.17%) subject never disclosed the diabetes diagnosis. Overall, results were similar between groups during HO. During RR minutes 4 and 5, the ΔR2 (difference in oxygen signal relative to baseline), was lower in the diabetic cohort compared to controls, with most significant decrease in T1DM (RR6) and T2DM (RR2, RR4) (Fig 1&2). Metabolic, inflammatory and vascular changes have been described in ex vivo placentas from diabetic pregnancies. Maternal hyperoxia during BOLD imaging reflects oxygen carrying capacity and transfer from the maternal circulation to the placenta and fetus. Decreased BOLD signaling suggests altered placenta function, reflecting either increased oxygen consumption of the diabetic placenta or continued oxygen transfer to the fetus. Additional studies to explore the clinical significance of these findings are underway.View Large Image Figure ViewerDownload Hi-res image Download (PPT)

Study of placental morphometric anatomy in mothers with gestational diabetes mellitus and inৎluence of gestational diabetes mellitus on the fetal weight

The placenta is an organ which is an indicator of maternal and fetal disorders. Gestational Diabetes mellitus complicates 2-5% of all pregnancy. Therefore our work was an analysis of changes in placental morphometric anatomy in mothers of gestational diabetes mellitus and the influence of gestational diabetes mellitus on the fetal weight. Sixty-two placentas of full-term pregnancy collected from labour room/operation theatre of Gynaecology and obstetrics, department of government medical college and super facility hospital Azamgarh, Uttar Pradesh. Out of sixty-two placentas, 31 are from mothers with no known history of preexisting gestational diabetes mellitus cases as controls and 31 collected from mothers with gestational diabetes mellitus. We found mean placental weight, mean placental area, mean placental volume, mean no of cotyledons significantly more in placentas of gestational diabetic mothers. Mean fetal weight of gestational diabetic mothers were more in comparison with controls. Mean transverse diameter of placentas of the diabetic mothers were more than mean transverse diameter of placentas of the non-diabetic mothers, statistically significant. Mean longitudinal diameter also more in placentas of diabetic mothers, not statistically significant. Mean thickness at the centre more in placentas of diabetic mothers, statistically significant. Mean thickness mid-way between centre and margin and mean thickness at margin more in diabetic placentas, not statistically significant. Gestational diabetic mothers had more round-shaped placentas. Marginal insertion of umbilical cord presents more in placentas of gestational diabetic mothers.

Prothymosin α activates type I collagen to develop a fibrotic placenta in gestational diabetes.

High-risk pregnancies, such as pregnancies with gestational diabetes mellitus (GDM), are becoming more common and as such, have become important public health issues worldwide. GDM increases the risks of macrosomia, premature infants, and preeclampsia. Although placental dysfunction, including fibrosis is associated with the development of GDM, factors that link these observations remain unknown. Prothymosin α (ProTα) is expressed in the placenta and is involved in cell proliferation and immunomodulation. It also plays an important role in insulin resistance and fibrosis. However, the role of ProTα in GDM is still unclear. In the present study, we found that fibrosis-related protein expressions, such as type I collagen (Col-1) were significantly increased in the placentae of ProTα transgenic mice. With elevated fibrosis-related protein expressions, placental weights significantly increased in GDM group. In addition, placental and circulating ProTα levels were significantly higher in patients with GDM (n=39), compared with the healthy group (n=102), and were positively correlated with Col-1 expression. Mice with streptozotocin (STZ)-induced GDM had increased ProTα, fasting blood glucose, Col-1, and placental weight, whereas plasma insulin levels were decreased. ProTα overexpression enhanced nuclear factor κB (NFκB) activation to increase fibrosis-related protein expressions in 3A-Sub-E trophoblasts, while treatment with an NFκB inhibitor reversed the effect of ProTα on fibrosis-related protein expressions. We further investigated whether ProTα is regulated by hyperglycemia-induced reactive oxygen species (ROS). In conclusion, ProTα increases the amount of placental connective tissue and thus contributes to the pathogenesis of placental fibrosis in GDM. Therefore, ProTα may be a novel therapeutic target for GDM.