Gestational Diabetes Mellitus Placentas Research Articles

Histological alterations of the placenta in gestational diabetes mellitus: Implications for fetoplacental transport and fetal outcome

Background: The placenta is a pivotal medium for physiological exchanges between the maternal and fetal circulations. However, diabetic insults early in gestation can influence the placental barrier, potentially impacting fetal development and outcomes. This study sought to understand the histological changes in the placentae of gestational diabetes mellitus (GDM) cases, highlighting the significance of these alterations on fetal health. Aims and Objectives: The primary aim of this research was to elucidate the histological changes present in the placentae of women diagnosed with GDM. Furthermore, the study sought to determine the implications of these changes on the standard placental anatomy and its associated functionalities, thereby assessing potential impacts on fetal development and outcomes. Materials and Methods: A case–control study was conducted at MES Medical College, Perinthalmanna, Kerala, from October 2014 to December 2018. Inclusion criteria considered pregnant women aged 19–38 years diagnosed with GDM, among other factors. Exclusion criteria weeded out pre-diagnosed diabetes cases, unclear glycemic statuses, and a range of pregnancy complications. Placentae samples underwent meticulous histological and histochemical analyses, focusing on key histological features, including syncytiotrophoblastic knots, vasculosyncytial membranes, and chorangiosis. Results: Significant histological variations were observed in GDM cases compared to controls. Notably, there was an increased formation of syncytial knots and reduced vasculosyncytial membranes in GDM placentae. In addition, chorangiosis was more prevalent, suggesting potential chronic prenatal hypoxia. Marked thickening of the syncytiotrophoblast basement membrane, villous edema, and fibrinoid necrosis were other pertinent findings in GDM cases, each with statistical significance (P < 0.001). Conclusion: The findings underscore the profound histological changes in the placenta associated with GDM, emphasizing the need for comprehensive maternal care and monitoring. These alterations can compromise fetoplacental transport and may have long-term implications on fetal health, highlighting the critical role of timely GDM diagnosis and intervention.

CD68 expression in the placenta of gestational diabetic mothers: A case-control study.

Gestational diabetes mellitus (GDM) is defined as any degree of glucose intolerance with the onset or first recognition during pregnancy and is the most common metabolic complication of pregnancy. Significant maternal and fetal complications can result from undiagnosed or inadequately treated GDM. To investigate the difference in the expression of the CD-68 marker in the Hofbauer cells (HCs) and their distribution within the villi in the placentas of diabetic and non-diabetic mothers. Sixty placentas were included in the study, 30 as controls and 30 from mothers with diagnosed GDM as cases. Full-thickness cross sections of placentas were obtained. Tissue processing was done, followed by haematoxylin and eosin (H&E). A study of CD68 markers (placental macrophages) was done using standard protocols of immunohistochemistry. Frequencies and percentages of Hofbauer cells (HCs) found in case and control placental tissue were calculated. Student's t-test was used to compare two groups using SPSS 13.0 software. When P is 0.0001, differences were considered statistically significant. We studied the distribution and number of fetal macrophages (CD68+) in diabetic and non-diabetic placentas. The immunostained CD68+ cell count was identified to be significantly higher in the GDM placenta. In relation to fetal blood vessels in the villus stroma of the GDM placenta in comparison to control, CD68+ cells were found more frequently. This study shows a significant increase in the number of Hofbauer cells in the placenta of mothers with GDM in comparison to control (P < 0.0001). An increase in macrophages in these placentae might be related to the protective mechanism against inflammation. Further studies are required to investigate the mechanism in detail.

Lower HLA-G levels in extravillous trophoblasts of human term placenta in gestational diabetes mellitus than in normal controls

The non-classical human leucocyte antigen (HLA) class I molecule HLA-G is widely known to play a major role in feto-maternal tolerance. We tested the hypothesis that HLA-G expression is altered in placentas of women with gestational diabetes mellitus (GDM) in a specific pattern that depends on fetal sex. HLA-G expression was analysed in a total of 80 placentas (40 placentas from women with GDM and 40 healthy controls) by immunohistochemistry using the semi-quantitative immunoreactive score (IRS). Double immunofluorescence staining identified the cells expressing HLA-G in the decidua and allowed evaluation of the expression pattern. We found a significant (p < 0.001) reduction of HLA-G expression in extravillous cytotrophoblasts (EVTs) in the placentas of women with GDM as compared to the healthy controls and were able to demonstrate that this downregulation was not due to a loss of cell number, but to a loss of expression intensity. A special change in the cell pattern of EVTs was observed, with these cells showing an obvious decrease in HLA-G expression on their cell surface. No significant differences according to fetal sex were found. These data show a possible association between decreased HLA-G expression and presence of GDM and provide new insights into altered placental function in women with GDM.

Identification of human placenta-derived circular RNAs and autophagy related circRNA-miRNA-mRNA regulatory network in gestational diabetes mellitus.

Gestational diabetes mellitus (GDM) is a metabolic and reproductive disease with serious risks and adverse health effects. However, the pathophysiological mechanism of GDM, especially the roles of circRNAs in its pathogenesis, is largely unknown. The objective of this study was to identify and investigate the roles of circRNAs in GDM. In the current study, placental circRNA expression profiles of normal controls and GDM patients were analyzed using high-throughput sequencing. Bioinformatics analysis identified a total of 4,955 circRNAs, of which 37 circRNAs were significantly deregulated in GDM placentas compared with NC placentas. GO and KEGG enrichment analyses demonstrated that metabolic process-associated terms and metabolic pathways that may be related to GDM were significantly enriched. The biological characteristics of placenta-derived circRNAs, such as their stability and RNase R resistance, were also validated Bioinformatics prediction. Moreover, we constructed the autophagy related circRNA-miRNA-mRNA regulatory network and further functional analysis revealed that the circCDH2-miR-33b-3p-ULK1 axis may be associated with autophagy in the placentas of GDM patients. Our study indicates that aberrant expression of circRNAs may play roles in autophagy in GDM placentas, providing new insights into GDM.

Aquaporin-8 overexpression is involved in vascular structure and function changes in placentas of gestational diabetes mellitus patients.

To study the role and mechanism of aquaporin-8 (AQP8) in placental vascular development in gestational diabetes mellitus (GDM), hematoxylin-eosin staining and immunohistochemistry were utilized to analyze the histopathological changes in placentas in GDM patients. Transwell, CCK-8, and tube formation assays were performed to examine cell migration, proliferation, and tube formation. AQP8, vascular cell adhesion molecule 1 (VCAM-1), tumor necrosis factor alpha (TNF)-α, and vascular endothelial growth factor (VEGF)-A expression levels were investigated. Relative to the control group, the placentas in the GDM group showed morphological changes, the number of microvessels in the placental villi arterioles was significantly higher, and the area of microvessels in the arterioles of placental villi was significantly lower. The expression levels of VCAM-1, TNF-α, VEGF-A, and AQP8 in the GDM placentas and human umbilical vein endothelial cells (HUVECs) stimulated by high glucose were significantly higher than those in the control group, and AQP8 was located in placental endothelial cells. Overexpression of glucose and AQP8 inhibited tube formation, migration, and proliferation in HUVECs. High glucose levels can induce dysfunction in vascular endothelial cells and lead to pathological changes in the placental vascular structure in GDM. AQP8 overexpression in placental GDM can inhibit endothelial cell behavior, cause endothelial cell dysfunction, and further participate in the occurrence and development of GDM placental vascular lesions.

HOXC8 alleviates high glucose-triggered damage of trophoblast cells during gestational diabetes mellitus via activating TGFβ1-mediated Notch1 pathway.

Gestational diabetes mellitus (GDM) is an increasingly frequent disease occurred during pregnancy. HOXC8 has been disclosed to take part in the regulation of cancers. Additionally, the HOXC8 expression was dramatically decreased in the placenta of pre-eclampsia patients, but its expression and function have not been investigated in GDM. In this work, it was demonstrated that the mRNA and protein expression of HOXC8 was lower in GDM placenta tissues and GDM cell model. In addition, HOXC8 facilitated trophoblast cell proliferation and weakened trophoblast cell mitochondrial apoptosis. HOXC8 enhanced trophoblast cell migration and angiogenesis. Moreover, HOXC8 activated the TGFβ1-mediated Notch1 signaling pathway. Results showed that the mRNA and protein expressions of TGFβ1 and Notch1 were both lower in the GDM group than that in the NP group. Besides, there were positive correlations among HOXC8, TGFβ1 and Notch1. Inhibition of TGFβ1 (SB202190 treatment) reversed the effects of HOXC8 on trophoblast cells through modulating cell proliferation, mitochondrial apoptosis, migration and angiogenesis. At last, through in vivo experiments, it was identified that HOXC8 relieved GDM symptoms in vivo. In conclusion, HOXC8 alleviated HG-stimulated damage of trophoblast cells during GDM through activating TGFβ1-mediated Notch1 pathway. This discovery may provide a novel and useful bio-target for GDM treatment.

Down-Regulation of PLAC1 in the Placenta of Gestational Diabetes Mellitus Patients and its Clinical Significance

Background: Placenta-specific 1 (PLAC1) is specifically expressed in the placenta and plays a fundamental role in placenta function. Aberrant expression of PLAC1 has been reported in pregnancy-related disorders; however, its expression in gestational diabetes mellitus (GDM) has not been clearly elucidated. This study aimed to investigate the expression of PLAC1 in the placenta of GDM patients, and its relationship with clinical characteristics. Methods: This was a case-control study. Placental tissues were collected from 37 GDM patients (GDM group) and 38 pregnant women with normal glucose tolerance (control group), matched with respect to maternal age and gestational weeks. We examined the expression of PLAC1 in the placenta of both groups and determined its association with clinical indicators. The localization of PLAC1 was confirmed by immunohistochemistry analyses. Results: PLAC1 expression was significantly lower in the placenta of GDM patients. For the control group, PLAC1 was positively correlated with pre-pregnancy body mass index (BMI), BMI at delivery, the fasting insulin, triglyceride levels, and homeostasis model assessment during delivery. In the case of GDM patients, there was no correlation between PLAC1 and these indices. Additionally, PLAC1 protein was mainly expressed in the cytoplasm of syncytiotrophoblasts and chorionic stromal cells. Conclusions: The expression of PLAC1 was reduced in the GDM placenta, which provides insight into the pathophysiological changes occurring in the placenta of these patients.

Gestational diabetes mellitus placentas exhibit epimutations at placental development genes

ABSTRACT Gestational diabetes mellitus (GDM) is a maternal metabolic disorder that perturbs placental development and increases the risk of offspring short- and long-term metabolic disorders. The mechanisms by which GDM impairs placental development remain poorly understood. Here, we defined the DNA methylome of GDM placentas and determined whether GDM perturbs methylation at genes important for placental development. We conducted an epigenome-wide association study of 42 placentas from pregnancies in the South African Soweto First 1000 days cohort (S1000). Using genome-wide bisulfite sequencing, we compared non-GDM placentas to GDM placentas with similar proportions from obese and non-obese mothers. Compared to non-GDM, GDM placentas exhibited a distinct methylation profile consisting of 12,210 differentially methylated CpGs (DMCs) that mapped to 3,875 genes. Epigenetically altered genes were enriched in Wnt and cadherin signalling pathways, both critical in placentation and embryogenesis. We also defined regional DNA methylation perturbation in GDM placentas at 11 placental development genes. These findings reveal extensive changes to the placental epigenome of GDM pregnancies and highlight perturbation enriched at important placental development genes. These molecular changes represent potential mechanisms for GDM-induced placental effects that may serve as candidate biomarkers for placental, maternal, and foetal health. Using a study design that used similar proportions of obese and non-obese mothers in our case and control pregnancies, we minimized the detection of changes due to obesity alone. Further work will be necessary to investigate the extent of the influence of obesity on these GDM-related placental epigenetic changes.

New Insights into Adipokines in Gestational Diabetes Mellitus.

Gestational diabetes mellitus (GDM) is the most common metabolic disorder of pregnancy and has considerable short- and long-term consequences for the health of both the mother and the newborn. Within its pathophysiology, genetic, nutritional, epigenetic, immunological, and hormonal components have been described. Within the last two items, it is known that different hormones and cytokines secreted by adipose tissue, known collectively as adipokines, are involved in the metabolic alterations underlying GDM. Although the maternal circulating profile of adipokines in GDM has been extensively studied, and there are excellent reviews on the subject, it is in recent years that more progress has been made in the study of their expression in visceral adipose tissue (VAT), subcutaneous adipose tissue (SAT), placenta, and their concentrations in the umbilical circulation. Thus, this review compiles and organizes the most recent findings on the maternal and umbilical circulating profile and the levels of expression of adipokines in VAT, SAT, and placenta in GDM.

Baicalein suppresses high glucose-induced inflammation and apoptosis in trophoblasts by targeting the miRNA-17-5p-Mfn1/2-NF-κB pathway

Controlling inflammation and apoptosis in trophoblasts is critical for treating gestational diabetes mellitus (GDM). Baicalein (Bai) exhibits anti-inflammatory and miRNA-related effects; however, its roles and mechanisms in GDM remain unknown. Therefore, we explored whether Bai inhibited inflammation and apoptosis in human trophoblasts (HTR8 cells) and analyzed its mechanisms. HTR8 cells pretreated with Bai were subjected to the high-glucose (HG) stimulation before analyzing their viability, cytokine production and apoptosis, followed the expression profiles of small RNA sequencing data. The effects of miR-17-5p on the inflammation, mitochondrial fission, and apoptosis were investigated by ELISA, transmission electron microscopy and flow cytometry, respectively. Moreover, miR-17-5p, Mfn1/Mfn2 levels and mitochondrial morphology in human plasma and placental tissues from GDM-complicated and normal pregnant women were examined. Bai decreased the secretion of TNF-α, IL-1β, IL-6 and apoptosis in HG-stimulated HTR8 cells, while miR-17-5p mediated the anti-inflammatory and anti-apoptotic effects of Bai. Mechanically, miR-17-5p targeted Mfn1/Mfn2 by affecting the mitochondrial fission and apoptosis via regulation of p-Drp1 (Ser 616) and p-NF-κB signaling. Moreover, overexpression of Mfn1/Mfn2 reversed miR-17-5p-elicited mitochondrial fission and inflammation in HG-stimulated HTR8 cells pretreated with Bai. Furhtermore, overexpression of Drp1 also reversed the anti-inflammatory effect of Mfn1/2 overexpression in HG-treated HTR8 cells via up-regulation of p65 phosphorylation. Finally, miR-17-5p was upregulated in human GDM plasma and placentas along with the reduced Mfn1/Mfn2. We are the first to demonstrate that bai exerts anti-inflammatory and anti-apoptotic effects on GDM, likely by targeting the miRNA-17-5p-Mfn1/2-NF-κB pathway.

N6-Methyladenosine-Related Gene Signature Associated With Monocyte Infiltration Is Clinically Significant in Gestational Diabetes Mellitus.

ObjectiveThe objective of this study was to reveal the potential crosstalk between immune infiltration and N6- methyladenosine (m6A) modification in the placentas of patients with gestational diabetes mellitus (GDM), and to construct a model for the diagnosis of GDM.MethodsWe analyzed imbalanced immune infiltration and differentially expressed m6A-related genes (DMRGs) in the placentas of patients with GDM, based on the GSE70493 dataset. An immune-related DMRG signature, with significant classifying power and diagnostic value, was identified using a least absolute shrinkage and selection operator (LASSO) regression. Based on the selected DMRGs, we developed and validated a nomogram model using GSE70493 and GSE92772 as the training and validation sets, respectively.ResultsInfiltration of monocytes was higher in GDM placentas than in control samples, while the infiltration of macrophages (M1 and M2) in GDM placentas was lower than in controls. A total of 14 DMRGs were strongly associated with monocyte infiltration, seven of which were significant in distinguishing patients with GDM from normal controls. These genes were CD81, CFH, FABP5, GBP1, GNG11, IL1RL1, and SLAMF6. The calibration curve, decision curve, clinical impact curve, and receiver operating characteristic curve showed that the nomogram recognized GDM with high accuracy in both the training and validation sets.ConclusionsOur results provide clues that crosstalk between m6A modification and immune infiltration may have implications in terms of novel biomarkers and therapeutic targets for GDM.

Increased Pro-Inflammatory T Cells, Senescent T Cells, and Immune-Check Point Molecules in the Placentas of Patients With Gestational Diabetes Mellitus.

Gestational diabetes mellitus (GDM) is the most common metabolic complication of pregnancy. To define the altered pathway in GDM placenta, we investigated the transcriptomic profiles from human placenta between GDM and controls. Clinical parameters and postpartum complications were reviewed in all participants. Differentially expressed canonical pathways were analyzed between the GDM and control groups based on transcriptomic analysis. CD4+ T, CD8+ T, and senescent T cell subsets were determined by flow cytometry based on staining for specific intracellular cytokines. Gene ontology analysis revealed that the placenta of GDM revealed upregulation of diverse mitochondria or DNA replication related pathways and downregulation of T-cell immunity related pathways. The maternal placenta of the GDM group had a higher proportion of CD4+ T and CD8+ T cells than the control group. Interestingly, senescent CD4+ T cells tended to increase and CD8+ T cells were significantly increased in GDM compared to controls, along with increased programmed cell death-1 (CD274+) expression. Programmed death-ligand 1 expression in syncytotrophoblasts was also significantly increased in patients with GDM. This study demonstrated increased proinflammatory T cells, senescent T cells and immune-check point molecules in GDM placentas, suggesting that changes in senescent T cells and immune-escape signaling might be related to the pathophysiology of GDM.

NLRP3 inflammasome activation in gestational diabetes mellitus placentas is associated with hydrogen sulfide synthetase deficiency.

The placenta may play a key role in the activation of inflammation and initiation of insulin resistance (IR) during gestational diabetes mellitus (GDM) pathogenesis. Interleukin (IL)-1β and IL-18, regulated by NLR family pyrin domain containing-3 (NLRP3) inflammasome, are important inflammatory cytokines in the initiation of maternal IR during GDM. However, the mechanism responsible for the regulatory of NLRP3 inflammasome in placenta remains unknown. Hydrogen sulfide (H2S) exerts anti-inflammatory function partially via suppressing the activation of the NLPR3 inflammasome. The present study aimed to investigate the role of NLRP3 inflammasome, H2S synthetase cystathionine-γ-lyase (CSE) and cystathionine-β-synthetase (CBS) in placenta in the pathogenesis of GDM. Clinical placenta samples were collected from pregnant women with GDM (n=16) and healthy pregnant women at term (n=16). Western blot analysis was performed to detect the protein expression levels of NLRP3, cleaved caspase-1, CBS and CSE in the placenta samples. Pearson's correlation analysis was performed to assess the correlation between NLRP3 inflammasome and H2S synthetase. Human placental cells were cultured and treated with different concentrations of NaHS (0, 10, 25 and 50 nmol/l) or L-cysteine (0, 0.25, 0.50 and 1.00 mmol/l). In addition, western blot analysis was performed to detect the protein expression levels of NLRP3 and cleaved caspase-1, while ELISA was performed to measure the production of IL-1β and IL-18 in the culture media. The results demonstrated that the expression levels of NLRP3 and cleaved caspase-1 increased, while the expression levels of CBS and CSE decreased in the placenta samples. In addition, the expression levels of NLRP3 and cleaved caspase-1 were inversely correlated with the expression levels of CBS and CSE. Notably, NaHS and L-cysteine significantly suppressed the expression levels of NLRP3 and cleaved caspase-1, and the production of IL-1 and IL-18 in human placental cells. Taken together, the results of the present study suggest that H2S synthetase deficiency in placenta may contribute to excessive activation of NLRP3 inflammasome in GDM.

Placental metabolic profiling in gestational diabetes mellitus: An important role of fatty acids.

AimGestational diabetes mellitus (GDM) is the most common metabolic disorder during pregnancy. Accumulating studies have reported metabolites that are significantly associated with the development of GDM. However, studies on the metabolism of placenta, the most important organ of maternal‐fetal energy and material transport, are extremely rare. This study aimed to identify and discuss the relationship between differentially expressed metabolites (DEM) and clinical parameters of the mothers and newborns.MethodsIn this study, metabolites from 63 placenta tissues (32 GDM and 31 normal controls) were assayed by ultra‐performance liquid chromatography‐high resolution mass spectrometry (UPLC‐HRMS).ResultsA total of 1297 annotated metabolites were detected, of which 87 significantly different in GDM placenta. Lipids and lipid‐like molecules accounted for 62.1% of DEM as they were significantly enriched via the “biosynthesis of unsaturated fatty acids” and “fatty acid biosynthesis” pathways. Linoleic acid and α‐linolenic acid appeared to be good biomarkers for the prediction and diagnosis of GDM. In addition, the level of PC(14:0/18:0) was negatively correlated with neonatal weight. 14 metabolites significantly different in male and female offspring, with the most increase in female newborns.ConclusionEven if maternal blood glucose level is well controlled, there are still metabolic abnormalities in GDM. Lipids and lipid‐like molecules were the main differential metabolites, especially unsaturated fatty acids.

Comparative analysis of miRNA expression profiles in small extracellular vesicles and their originating primary human trophoblast cells from normal and Gestational Diabetes Mellitus placentae

Comparative analysis of miRNA expression profiles in small extracellular vesicles and their originating primary human trophoblast cells from normal and Gestational Diabetes Mellitus placentae

942-P: The Choline Metabolite TMAO Inhibits NETosis and Promotes Placental Development in GDM of Humans and Mice

Objective: Trimethylamine N-oxide (TMAO) is a choline metabolite and has been reported as a risk factor of gestational diabetes mellitus (GDM). Diabetes primes neutrophils to produce neutrophil extracellular traps (NETosis). We investigated the effect of TMAO and NETs on the placenta and revealed the role of TMAO and NETs in GDM. Methods: Peripheral plasma, cord plasma and placenta from normal pregnant and GDM women were collected. Plasma concentrations of TMAO, ds-DNA and myeloperoxidase (MPO) were compared and association analysis was performed. HTR-8/Svneo cells and GDM models of wild-type and PAD4-/- mice were used to observe the effect of TMAO and NETs on the placenta. Results: The peripheral and cord plasma TMAO levels of GDM women were significantly higher than those of control. BMI and glucose levels were positively correlated with the concentration of blood TMAO, especially the newborn weight and placental thickness were positively correlated with TMAO levels in cord blood. TMAO could promote proliferation, migration, invasion and angiogenesis of HTR-8/Svneo cells, and TMAO-treated neutrophils could resist NETosis stimulated by PMA or LPS. Plasma concentrations of ds-DNA and MPO in peripheral and cord blood were significantly higher in GDM women, and BMI and blood glucose levels were positively correlated with ds-DNA and MPO levels. MPO levels from GDM placenta were also higher than those in the control group. NETs inhibit the proliferation, migration, invasion and angiogenesis of HTR-8/Svneo cells. The placenta weight of PAD4-/- mice was significantly higher than that of wild-type mice. TMAO feeding also significantly increased the weight of the placenta and fetuses, and this increase did not affect the normal structure of the placenta. Conclusion: Higher TMAO levels and abnormal NETosis were associated with GDM. TMAO could not only promote the development of the placenta and fetus, but also inhibit NETosis to protect the placenta. Disclosure X. Lin: None. Y. Zhang: None. X. He: None. N. Chen: None. M. Wang: None. Y. Chen: None. X. Xiao: None. Funding National Natural Science Foundation of China (82071734, 81871222)

Transcriptomic Profiling of Human Placenta in Gestational Diabetes Mellitus at the Single-Cell Level.

Gestational diabetes mellitus (GDM) is associated with an increased risk of adverse pregnancy outcomes. Increasing evidence shows that placentation defects may play important roles in GDM. However, our understanding of the human placenta remains limited. In this study, we generated a comprehensive transcriptomic profile of cellular signatures and transcriptomes in the human placenta in GDM using single-cell RNA sequencing (scRNA-seq), constructed a comprehensive cell atlas, and identified cell subtypes and subtype-specific marker genes. In addition, we investigated the placental cellular function and intercellular interactions in GDM. These findings help to elucidate the molecular mechanisms of GDM, and may facilitate the development of new approaches to GDM treatment and prevention.

Placental structural abnormalities in gestational diabetes and when they develop: A scoping review.

Gestational diabetes mellitus (GDM) is defined as diabetes with onset or first recognition during gestation. It is a common complication of pregnancy that has become more prevalent over the past few decades. Abnormalities in fetal growth, including increased incidence of both large and small for gestational age babies, suggest placental dysfunction. The major goal of this scoping review is to determine what is known about abnormalities in placentas delivered from GDM pregnancies, and how early in gestation these abnormalities arise. A secondary goal is to review to what extent other selected factors, in particular obesity, have been found to influence or modify the reported effects of GDM on placental development, and whether these are considered in the study of GDM placentas. PubMed and Scopus databases were searched using the key terms: "gestational diabetes AND (woman OR human) AND placenta AND (ultrasound OR ultrastructure OR imaging OR histology OR pathology). Studies of gross morphology and histoarchitecture in placentas delivered from GDM pregnancies consistently report increased placental size, villous immaturity and a range of vascular lesions when compared to uncomplicated pregnancies. In contrast, a small number of ultrasound studies have examined placental development in GDM pregnancies in the second, and especially, the first trimester. Relatively few studies have analyzed interactions with maternal BMI, but these do suggest that it may play a role in placental abnormalities. Further examination of placental development early in pregnancy is needed to understand when it becomes disrupted in GDM, as a first step to identifying the underlying causes.

Placental Antioxidant Defenses and Autophagy-Related Genes in Maternal Obesity and Gestational Diabetes Mellitus

Maternal obesity and gestational diabetes mellitus (GDM) are increasing worldwide, representing risk factors for both mother and child short/long-term outcomes. Oxidative stress, lipotoxicity and altered autophagy have already been reported in obesity, but few studies have focused on obese pregnant women with GDM. Antioxidant and macro/chaperone-mediated autophagy (CMA)-related gene expressions were evaluated herein in obese and GDM placentas. A total of 47 women with singleton pregnancies delivered by elective cesarean section were enrolled: 16 normal weight (NW), 18 obese with no comorbidities (OB GDM(–)), 13 obese with GDM (OB GDM(+)). Placental gene expression was assessed by real-time PCR. Antioxidant gene expression (CAT, GPX1, GSS) decreased, the pro-autophagic ULK1 gene increased and the chaperone-mediated autophagy regulator PHLPP1 decreased in OB GDM(–) vs. NW. On the other hand, PHLPP1 expression increased in OB GDM(+) vs. OB GDM(–). When analyzing results in relation to fetal sex, we found sexual dimorphism for both antioxidant and CMA-related gene expressions. These preliminary results can pave the way for further analyses aimed at elucidating the placental autophagy role in metabolic pregnancy disorders and its potential targetability for the treatment of diabetes outcomes.

English

BACKGROUND Placenta is a multifunctional fetomaternal organ that plays an important role during pregnancy. Gestational diabetes mellitus (GDM) is reflected on placenta both macroscopically and microscopically as enlargement of placenta, abnormalities in villi and degenerative changes. METHODS This is a cross sectional study conducted among two groups, normal group and GDM group, to compare the gross features of GDM placentae in the Department of Obstetrics and Gynaecology and Department of Anatomy, Govt. Medical College, Thiruvananthapuram. RESULTS The study was conducted on 65 normal and 65 GDM placentae. There was an increased incidence of gestational diabetes mellitus in the age group &gt; 25 years with a mean age of 26.38 ± 3.84 years. Multiparous women have been found to be more prone to gestational diabetes mellitus. Past history of abortions and intrauterine death (IUD) was more in GDM group as compared to normal group. Incidence of lower segment caesarean section (LSCS) was also more in GDM group. Weight, diameter and number of maternal cotyledons of placentae were significantly increased in GDM. The predominant shape of placenta in both groups was round, next to that was oval. Only 3 placentae showed irregular shape and that was from GDM group. Most common type of attachment of umbilical cord was eccentric in both groups. Next to that was central and marginal respectively. Only one placenta was furcate and that belonged to GDM group. Fetal membrane was translucent in all normal and GDM placentae. Mean birth weight of the baby of GDM mothers was significantly increased. Mean fetoplacental weight ratio was significantly decreased in GDM group as compared to normal group. CONCLUSIONS In the present study, GDM placentae showed significant changes in gross features. Meticulous gross examination of a placenta prior to histologic sectioning enhances microscopic interpretation. By increasing our understanding of the placenta, it may be possible to prevent and treat placental abnormalities related to GDM, thus ensuring lifelong health of the child and the mother. Hence, the present work would provide vital information to both obstetricians and neonatologists. KEY WORDS Placenta, Gestational Diabetes Mellitus, Morphology of Placenta