Normal Pregnancy Group Research Articles

Changes in the Gut Metabolic Profile of Gestational Diabetes Mellitus Rats Following Probiotic Supplementation.

The roles of gut microbiota and metabolomics in women with gestational diabetes mellitus (GDM) are not well understood. This study investigated the gut metabolomic profiling of GDM rats and GDM rats treated with probiotic supplements. Associations between gut metabolites and microbiota were also studied in GDM rats. Liquid chromatography–mass spectrometry was used to detect gut metabolites in GDM rats and GDM rats treated with probiotic supplements of 0.5 g (low-dose group) or 1 g (high-dose group) for 15 days. Each gram of probiotic supplement contained 5 × 107 colony-forming units (CFU) of Lactobacillus rhamnosus LGG and 1 × 108 CFU of Bifidobacterium animalis subspecies lactis Bb12. The association between gut metabolites and microbiota in GDM rats was investigated using Spearman’s correlation. Finally, 10 rats in the normal pregnant group, eight rats in the GDM model group, eight GDM rats in the low-dose probiotics group, and nine GDM rats in the high-dose probiotics group were further studied. Serum parameters and pancreatic and colon histology were significantly changed in GDM rats, and these were restored using probiotic supplements. In total, 999 gut metabolites were detected in the feces, and GDM rats were distinguished from normal rats. The levels of 44 metabolites were increased in GDM rats, and they were alleviated using probiotic supplements. Changes in metabolites in GDM rats were associated with amino acids and bile acids metabolism signaling pathways. Furthermore, changes in metabolites after probiotic supplementation were associated with porphyrin and chlorophyll metabolism pathways. We found that the Allobaculum genus displayed strong positive correlations, whereas the Bryobacter and Gemmatimonas genera displayed strong negative correlations with metabolisms of amino acids and bile acids in GDM rats. The Lactobacillus and Bifidobacterium genera were positively correlated with gut metabolites. Overall, our results showed that metabolism signaling pathways of amino acids and bile acids are associated with the development of GDM. Probiotic supplements alleviate the pathology of GDM through the metabolism pathways of amino acids, bile acids, porphyrin, and chlorophyll.

The relationship between free fatty acids and mitochondrial oxidative stress damage to trophoblast cell in preeclampsia

AimTo investigate the effects of free fatty acids on mitochondrial oxidative stress and the pathogenesis of preeclampsia.MethodsHuman primary trophoblast cells at 6–8 weeks of gestation were retrieved and cultured to 70–80% confluence, then incubated in serum from women with a normal pregnancy (normal pregnancy group), women with preeclampsia (PE group), and a combination of serum from women with 24 h preeclampsia-like symptoms and free fatty acids (FFA group). Mitochondrial membrane potential was assessed by fluorescent dye concurrent with detection of membrane channel conversion pore activity by fluorescence microscope. Enzyme labeling instruments and RT-PCR were used to detect mitochondrial DNA (mtDNA) levels.ResultsThe preeclampsia and free fatty acids groups both exhibited significantly higher levels of mitochondria oxidative stress damage when compared to the normal pregnancy group. However, no significant differences in mitochondrial oxidative stress damage were observed between the FFA and PE groups.ConclusionsSerum free fatty acids might play an important role in the pathogenesis of preeclampsia by enhancing mitochondrial oxidative stress damage.

Gestational weight gain and blood pressure control in physiological pregnancy and pregnancy complicated by hypertension.

Obesity is a widely recognised risk factor for chronic and gestational hypertension. Influence of gestational weight gain on blood pressure control throughout the pregnancy is not well characterised. Women in the third trimester of a singleton pregnancy were recruited to the study. Medical records were analysed and a special survey was conducted to obtain history on hypertensive disorders in pregnancy and weight changes during pregnancy. Blood pressure measurements were taken during the office visit in line with international guidelines. Relationships between gestational weight gain and maximal and office values of systolic and diastolic blood pressure values were analysed. Data of 90 women in normal pregnancy, 40 with gestational hypertension and 21 with chronic hypertension were analysed. Gestational weight gain was 11.9 ± 4.6 kg in the normal pregnancy group, 13.0 ± 5 kg in the gestational hypertension group and 10.6 ± 3.4 kg in the chronic hypertension group. Gestational weight gain positively correlated with both office (r = 0.48; p < 0.001) and maximal blood pressure values (r = 0.34; p = 0.004) in normal pregnancy and with maximal blood pressure values (r = 0.57; p = 0.02) in women with chronic hypertension. No correlation was observed between gestational weight gain and blood pressure values among women with gestational hypertension. In normal pregnancy and in women with chronic hypertension greater gestational weight gain is related to higher blood pressure values in the third trimester.

Angiotensin 1-7 and its analogue decrease blood pressure but aggravate renal damage in preeclamptic mice.

Preeclampsia (PE) is a multisystem disease that affects the health of both the pregnant women and the fetus during pregnancy. Agonistic autoantibodies to the angiotensin II type I receptor (AT1-AA) play a significant role in the pathogenesis of PE. This study aimed to determine the effects of Angiotensin 1-7 (Ang 1-7) and its analogue AVE0991 on AT1-AA-induced PE model. Pregnant mice were divided into five groups: the normal pregnant group, AT1-AA-induced preeclampsia group, and AT1-AA-induced preeclampsia group treated with Losartan, Ang 1-7, and AVE0991, respectively. AT1-AA-induced PE model was established on gestational day 13 by tail intravenous injection of purified AT1-AA polyclonal antibody from serum of guinea pigs. Blood urea nitrogen (BUN), urine albumin and urinary creatinine were measured on day 18 of pregnancy. The systolic blood pressure (SBP) was measured from gestational day 13 to day 18. Renal structure changes were observed via light and electron microscopy. Compared with the normal pregnant group (NP group), AT1-AA-induced preeclampsia group (PE group) exhibited elevated blood pressure and proteinuria, consistent with the characteristics of PE. Ang 1-7 or AVE0991 treatment decreased blood pressure without showing renoprotective effects. The findings indicated that Ang 1-7 and its analogue reduced blood pressure but aggravated renal damage in AT1-AA-induced PE mice.

CARDIOVASCULAR RISK IN WOMEN WITH PREECLAMPSIA.

In this study, possible biochemical and functional cardiovascular markers were assessed in women with preeclampsia. Fifty-five pregnant women with manifest moderate (mild) preeclampsia (PE) and fifty healthy women as a control group were included in this prospective study. Laboratory tests including lipid panel, C-reactive protein (CRP), and homocysteine levels as biohumoral markers of atherogenesis, as well as ergometry and the main cardiovascular risk factor markers were performed in all women during pregnancy and six months after delivery. In our study, cholesterol and LDL levels in the PE group did not differ from those in the control group. Triglyceride levels in the PE group were higher than the corresponding values found in normal pregnancies, while HDL levels were significantly lower in the PE group than in the normal pregnancy group (p<0.001). The values of total cholesterol, LDL, HDL, and triglycerides in the PE group were higher compared to those in the same group six months after delivery (p<0.001). The effect of PE as an inflammatory disease could be confirmed to a certain extent by elevated CRP levels (p<0.001). A very high percentage of negative exercise stress tests indicated a good cardiovascular response to the current PE in the otherwise healthy pregestational women. It could be concluded that the development of possible cardiovascular comorbidities in preeclamptic pregnant women is a long process, but also due to etiologic factors of coexistent metabolic disorders such as dyslipidemia, as well as elevated inflammatory markers and homocysteine, PE can be considered even an early predictor of cardiovascular disease.

Comparisons of urine protein-to-creatinine ratios and their dynamic change patterns during labor at term between normal pregnant women and women with pregnancy induced hypertension.

Introduction: To evaluate patterns of change in the urine protein-to-creatinine ratios (uPCRs) during labor at term between normal and women with pregnancy-induced hypertension (PIH).Methods: This is an observational study in tertiary referral hospital, recruiting 269 women at term delivery in Taiwan from April 19, 2019 to April 18, 2021. uPCRs in four phases (latent, active, recovery and early postpartum) and related clinical data at delivery were collected. Multivariate analyses with a linear regression model were performed to analyze continuous variables after adjusting for clinical data between two groups.Results: Based on exclusion criteria, 68 normal and 24 pregnant women with PIH were included. There were no differences in the uPCR or the proportion cases of uPCRs ≥ 300 mg/g between normal and PIH group in the four phases. There was a statistically significant tendency for the proportion of uPCRs ≥ 300 mg/g to increase from the latent to the early postpartum phase in both groups. The proportion of uPCRs ≥ 300 mg/g significantly increased from the active to the recovery phase and then declined from the recovery to the early postpartum phase in the normal group. Thus no differences in uPCRs cases change between any two phases in women with PIH, except the duration above stated.Conclusion: This is the first study to demonstrate that uPCRs data are not different between normal pregnant and PIH groups during the course of labor, but it did show different dynamic change patterns throughout the labor phases.

Methylation-reprogrammed CHRM3 results in vascular dysfunction in the human umbilical vein following IVF-ET†.

Assisted reproductive technology (ART) has been used globally among infertile couples. However, many epidemiological investigations have indicated that ART is associated with a range of long-term adverse health outcomes in offspring, including cardiovascular disease, obesity, and increased plasma lipid levels. Until now, direct evidence has been limited regarding the pathological changes in vascular function in fetuses with ART. In this study, human umbilical cords were collected from healthy normal pregnancies and in vitro fertilization and embryo transfer (IVF-ET) pregnancies. Vascular functional studies involving acetylcholine (ACh), antagonists of its specific receptors, and L-type calcium channel/PKC-MLC20 phosphorylation pathway specific inhibitors were conducted. Quantitative real-time PCR, Western blotting, and methylation analyses were performed on umbilical vein samples. We found that the umbilical vein constriction induced by ACh in the IVF-ET group was significantly attenuated compared with that in the healthy normal pregnancy group, which was not only associated with the hypermethylation of ACh muscarinic receptor subtype 3 (CHRM3) and decreased expression of CHRM3, PKCβ, and CaV1.2, but was also related to the reduced phosphorylation of MLC20. This study revealed that the hypermethylation of CHRM3, leading to a reduction in CHRM3 expression and downregulation of the CaV1.2/PKC-MLC20 phosphorylation pathway, was responsible for the decreased sensitivity to ACh observed in the umbilical vein under IVF-ET conditions. The hypermethylation of CHRM3 caused by IVF-ET might play an important role in altered vasoconstriction and impact cardiovascular systems in the long run.

Differences in maternal soluble ST2 levels in the third trimester of normal pregnancy versus preeclampsia.

BackgroundPreeclampsia is associated with intense inflammatory response in pregnancy, and soluble ST2 (sST2) is pathologically increased in this condition. No data exist regarding maternal sST2 levels in normal pregnancy versus preeclampsia in areas of southeast Asia with an ethnic Malay predominance.Materials and MethodsPatients were sorted into normal pregnancy or preeclampsia. Patients with a history of allergic, inflammatory, or malignant disease were excluded. One sample was taken per patient; all samples were taken during the third trimester of pregnancy. Thirty samples from each group were enrolled in the study, totaling 60 samples. Soluble ST2 levels in maternal plasma were measured using the Presage® ST2 Assay according to manufacturer instructions, and data was analyzed using SPSS 23.ResultsPatients in the preeclampsia group were significantly older than those in the normal pregnancy group (p = 0.01). Most patients with preeclampsia presented as early-onset (n = 23). Both systolic blood pressure (SBP) and diastolic blood pressure (DBP) were significantly higher (p < 0.001) in the preeclampsia group. Mean sST2 level in the preeclampsia group (85.89 ng/ml) was significantly higher than the normal pregnancy group mean (38.3 ng/ml) during the third trimester (p < 0.001). This study also found a correlation between sST2 and preeclampsia (p < 0.001, r = 0.480), SBP (p < 0.001, r = 0.407), and DBP (p = 0.007, r = 0.342), while preeclampsia was found to be the best explanatory variable of sST2 levels (r = 0.468, p < 0.001). sST2 level> 63.66 ng/ml has sensitivity 50% and specificity 93.3%, with AUC of 0.78 [95% CI 0.66 – 0.90], p < 0.001. The sST2 > 63.66 ng/ml has an OR of 14.0 [95% CI 2.82 – 69.6], p < 0.001 for preeclampsia. The dose-response relationship between sST2 level and preeclampsia was linear.ConclusionSoluble ST2 levels were increased in both normal pregnancy and preeclampsia but were significantly higher in patients with preeclampsia. Preeclampsia was also found to be the best explanatory variable for the increase of sST2 levels in ethnic Malay predominance.

Correlation between Apelin and Some Angiogenic Factors in the Pathogenesis of Preeclampsia: Apelin-13 as Novel Drug for Treating Preeclampsia and Its Physiological Effects on Placenta.

Preeclampsia (PE) is one of the commonest causes for maternal and fetal morbidity and mortality. Imbalances of angiogenic factors, oxidative stress, and inflammatory response have a role in the pathogenesis of PE. Data regarding the circulating apelin level and its role in PE remains controversial. This study was formulated to assess the serum apelin level in PE, investigate its correlation with some inflammatory, oxidative stress, and angiogenic proteins in a nitric oxide synthase inhibitor; the N (gamma)-nitro-L-arginine methyl ester (L-NAME)-induced rat model of PE and determine whether apelin administration could protect against development of PE. 40 healthy adult female albino rats and 10 adult male albino rats were used in this study. The pregnant female rats were randomly divided into three groups: group 1 (normal pregnant group), group 2 (PE-induced group), injected subcutaneously with 75 mg L-NAME/kg bodyweight/day starting from day 9 to 20 of gestation, and group 3 (PE-induced group supplemented with apelin (PE + apelin)); PE induced as before and simultaneously subcutaneously injected with apelin-13 (6 × 10−8 mol/kg bodyweight/twice daily) beginning from day 6 to 20 of gestation. In all groups, blood pressure and urine protein were determined at gestation days (GD) 0, 10, and 18. Moreover, serum apelin, placental growth factor (PLGF), vascular endothelial growth factor (VEGF), soluble fms-like tyrosine kinase-1 (sFlt-1), soluble endoglin (sEng), interferon-gamma (IFN-γ), and interleukin-10 (IL-10) levels and serum superoxide dismutase enzyme (SOD) and catalase (CAT) activities of all groups were estimated at the end of experiment. Placental histopathological examination was also performed. PE-induced rats showed significantly decreased serum apelin levels. Moreover, they showed significantly increased blood pressures, urine proteins, sFlt-1, sEng, and IFN-γ (mean arterial blood pressure, urine proteins, sFlt-1, sEng, and IFN-γ showed significant negative correlations with serum apelin level), but it showed significantly decreased VEGF, PLGF, IL-10, SOD, and CAT (VEGF, PLGF, IL-10, and SOD showed significant positive correlations with serum apelin level). In contrast, exogenous apelin administration significantly ameliorated these parameters together with improvement in the placental histoarchitecture in the apelin-supplemented PE group. This study demonstrated the protective effects of apelin administration on the pathogenesis of PE.

Proteomics Analysis of Serum Proteins in Gestational Diabetes.

Objective The purpose of this study was to screen serum proteins for biomarkers of gestational diabetes mellitus (GDM) and to investigate its pathogenesis by analyzing the differences in serum proteomics between pregnant women with GDM and healthy pregnant women. Methods Patients who were admitted to the First Affiliated Hospital of Fujian Medical University from June 2019 to January 2020 were included. According to the medical history and the results of the 75 g oral glucose tolerance test (OGTT), they were divided into the normal pregnant women group and GDM pregnant women group. The serum of two groups of patients was collected. High performance liquid chromatography-mass spectrometry was used to identify differentially expressed serum proteins between pregnant women with GDM and healthy pregnant women, and bioinformatics analysis was then performed on the identified proteins. Results A total of 1152 quantifiable proteins were detected; among them, 15 were upregulated in serum of GDM pregnant women, while 26 were downregulated. The subsequent parallel reaction monitoring (PRM) assay validated the expression levels of 12 out of 41 differentially expressed proteins. Moreover, bioinformatics analysis revealed that the differentially expressed proteins are involved in multiple biological processes and signaling pathways related to the lipid metabolism, glycan degradation, immune response, and platelet aggregation. Conclusions This study identified 41 serum proteins with differential expression between pregnant women with GDM and healthy pregnant women, providing new candidate molecules for elucidating GDM pathogenesis and screening therapeutic targets.

To Study the Clinico-Hematological Profile of Pre-Eclampsia on Mother and Newborns

Pre-eclampsia is a significant cause of maternal, fetal, and neonatal morbidities and mortalities associated with pregnancy. We aimed at examining the impact of maternal pre-eclampsia on new-borns’ and Mother’s hematological profile. OBJECTIVE: To study the hematological profile in mothers suffering from pre-eclampsia. To study the hematological profile in neonates. MATERIAL AND METHOD: The present cross-sectional study includes 100 pregnant womens and 100 neonates were included in the study and were grouped as under. Group 1: 50 normal pregnant womens. Group II: 50 Normal Neonates of mothers having normal pregnancy Group III: 50 pregnant mothers with gestational age between 32 and 36 weeks with preeclampsia. Group IV: 50 Neonates of mothers having pre-eclampsia. RESULT: Comparatively lower platelet count in preeclamptic women as compared to normal pregnant women. Also, total leucocyte count was relatively on lower side. Neutrophils and monocytes were raised in preeclamptic women when compared with normal pregnant women. Rest of all the parameters were not significantly affected. Clearly shows that in case of new-borns of mothers who are preeclamptic, haemoglobin and red blood cell count were significantly lowered. But platelet counts and total lymphocyte count was raised when compared with new-borns of normal pregnant women. CONCLUSION: Positive correlation between preeclampsia and neonatal thrombocytopenia. Prematurity, insufficiency of the placenta and fetal development restriction and need for neonatal resuscitation in babies born to pre-eclamptic women were found to be substantially higher compared to those born to stable normotensive people.

Carnitine palmitoyltransferase 1A is essential for decidualization in mice

Decidualization accompanies with extensive stromal cell proliferation and differentiation, is a crucial step in early pregnancy. Aberrant decidualization is linked to infertility and miscarriage but the mechanisms remain unclear. Carnitine palmitoyltransferase 1A (CPT1A) is an enzyme catalyzing key steps in the fatty acid beta-oxidation pathway. The objective of this study was to investigate the role of CPT1A in decidualization during early pregnancy. An increased expression of CPT1A was found both in Days 6 and 7 as compared with in Days 1, 4 and 5. Further examination showed that on days 5–7 of pregnancy, the protein level of CPT1A was strongly up-regulated at implantation sites compared with inter-implantation sites, the location of CPT1A protein was distributed in the decidual zone. Upon further exploration, CPT1A expression was significantly increased in response to artificially induced decidualization both in vivo and in vitro. After down-regulating CPT1A expression by CPT1A-small interfering RNA (siCPT1A) in primary mouse endometrial stromal cells, expressions of decidualization markers and cell proliferation markers were decreased. After siCPT1A was transfected into the mouse uterus, decidualization impaired and then led to the loss of the implanted embryos. Thus, CPT1A is important for decidualization in mice and it may regulate the stromal cell proliferation progress. It is worth noting that the expression of CPT1A protein of human decidua was significantly decreased in spontaneous abortion groups compared to normal pregnancy groups. Collectively, CPT1A is essential for endometrium of early pregnant mice and humans.

Levels of inter-alpha-trypsin inhibitor heavy chain H4 urinary polypeptide in gestational diabetes mellitus

ABSTRACT Gestational diabetes mellitus (GDM) can cause a variety of adverse maternal and fetal complications. The purpose of this study was to screen and identify the urinary polypeptides related to the severity of GDM and to analyze the correlation between urinary peptide levels and neonatal metabolic indices. A total of 31 normal pregnant women (N group) and 74 patients with GDM (GDM group) were randomly selected between February 2018 and August 2019. Patients with GDM were divided into two groups according to their fasting plasma glucose (FPG) levels. The urine samples were enriched using weak cation-exchange magnetic beads (MB-WCX), and eight different urine polypeptides were screened and analyzed. The peptide spectra were obtained using matrix-assisted laser desorption ionization time-of-flight mass spectrometry (MALDI-TOF MS). The urinary peptide signatures of the two groups were compared using the BioExplorer software. The difference analysis of the eight urinary polypeptides between the normal pregnant (N) group and GDM group showed that two polypeptides with mass-to- charge ratios (m/z) of 2175.7 and 2318.8, respectively, were significantly different between the two groups (P < 0.01). The m/z 2175.7 polypeptide was analyzed by liquid chromatography-tandem mass spectrometry (LC-MS), and the corresponding name of the molecule was inter-alpha-trypsin inhibitor heavy chain H4 (ITIH4). The changes in ITIH4 levels correlated with those in the neonatal metabolic indices. By establishing the Fisher discriminant function equation for the GDM group, the difference in sample distribution and mean value of the two groups could be observed directly. Abbreviations: GDM: gestational diabetes mellitus; FPG: fasting plasma glucose; MB-WCX: weak cation exchange magnetic beads; MALDI-TOF MS: matrix-assisted laser desorption ionization time-of-flight mass spectrometry; m/z: mass charge ratio; LC-MS: liquid chromatography-tandem mass spectrometry; glycosylated hemoglobin (HbA1c); PPG: postprandial plasma glucose; ITIH4: inter-alpha-trypsin inhibitor heavy chain H4; IR: insulin resistance; NFPG: neonatal fasting plasma glucose; NH: neonatal height; NW: neonatal weight; BMI: body mass index; RPL: recurrent pregnancy loss; OGTT: oral glucose tolerance test; ADA: American Diabetes Association; LIS: Laboratory Information System

LncRNA RPL13p5 gene expression promotes insulin resistance in patients with gestational diabetes.

Gestational diabetes mellitus (GDM) is a universal disease caused by a combination of environmental and genetic factors and resulting in abnormal signaling pathway function and eventual islet cell insufficiency. According to co-expression profile network data between messenger RNA (mRNA)-long non-coding RNA (lncRNA) in our laboratory, we selected lncRNA RPL13P5 as a candidate lncRNA related to the GDM insulin signaling pathway and which is upregulated in GDM patients. The study included a gestational diabetes group (n=25) and normal pregnancy group (n=19). Expression was detected by quantitative polymerase chain reaction (qPCR) and showed the expression levels of lncRNA RPL13P5 in peripheral blood were significantly different between the two groups (P<0.05). The correlation between the homeostasis model assessment insulin resistance (HOMA-IR) and lncRNA expression was analyzed. The lncRNA RPL13p5 forms a co-expression strand with the TSC2 gene via the PI3K-Akt signaling pathway. The sequencing of lncRNA RPL13P5 showed high expression and the qPCR validation results were consistent with the sequencing results. An association was observed between the expression level of lncRNA RPL13P5 and other clinicopathological features of GDM. LncRNA RPL13P5 forms a co-expression chain with the TSC2 gene through the PI3K-Akt signaling pathway and becomes part of the process of insulin resistance in GDM.

Assessment of serum afamin in patients with preeclampsia at third trimester

Preeclampsia (PE) is a multisystem disorder associated with pregnancy. It is accompanied by a ten percent global neonatal and perinatal mortality rate. Human afamin (AFM) is a glycoprotein which bind vitamin E. It is primarily developed by hepatocytes in the liver and then secreted into the blood. Elevated serum afamin levels have been reported in hypertensive pregnancy complications such as Pregnancy Induced Hypertension (PIH). To evaluate afamin levels in preeclamptic women at third trimester and explore if there is any relation between Afamin and severity of preeclampsia, a case control study was performed in Chemistry and Biochemistry Department, College of Medicine, Al-Nahrain University, Baghdad, Iraq from July 2019 to March 2020. Forty-one patients and 30 participants in control group (normal pregnant women) joined this study. The preeclamptic and normal pregnancies were taken with cluster random sampling method. Afamin (AFM) levels were measured by enzyme-linked immune sorbent assay (ELISA). Serum afamin (AFM) was significantly (p < 0.05) elevated in pregnant women with preeclampsia 2.34 ±0.23 (ng/mL) compared with that in normal pregnant women group 1.63± 0.19 (ng/mL). Although serum AFM concentration significantly increased in Preeclamptic women, there was no significant association differences between mild and sever groups.

Long-chain polyunsaturated fatty acid (LC-PUFA) status in severe preeclampsia and preterm birth: a cross sectional study

Long-Chain Polyunsaturated Fatty Acid (LCPUFA) is essential throughout pregnancy, since deficiency of LPUFA may linked to obstetrical complications. This study aimed to investigate LCPUFA status in severe preeclampsia and preterm birth. A cross sectional study was conducted in 104 pregnant women, which divided into normal pregnancy, severe preeclampsia and preterm birth groups. Serum percentage and concentration of total LCPUFA, omega-3, alpha-linolenic acid (ALA), eicosapentaenoic acid (EPA), docosahexaenoic acid (DHA), omega-6, linoleic acid (LA), and arachidonic acid (AA) were measured using gas chromatography/mass spectrometry. Receiver operating characteristic (ROC), bivariate and multivariate analysis were performed. Severe preeclampsia showed the highest concentration of total PUFA and the lowest DHA percentage, with significantly higher Omega-6/Omega-3 ratio (p = 0.004) and lower omega-3 index (p < 0.002) compared to control. Preterm birth showed the least omega-3 concentrations, with significantly low omega-6 derivates (LA (p = 0.014) and AA (p = 0.025)) compared to control. LCPUFA parameters have shown to increase the risk in both conditions, particularly ALA ≤ 53 µmol/L in preeclampsia with OR 5.44, 95%CI 1.16–25.42 and preterm birth with OR 4.68, 95%CI 1.52–14.38. These findings suggest that severe preeclampsia and preterm birth have an imbalance in LCPUFA status.

Study of serum electrolytes, calcium and magnesium in preeclampsia at a tertiary hospital in central Karnataka

Preeclampsia(PE) is a hypertensive disorder affecting about 5-14% of pregnancies worldwide and around 20% of high-risk pregnancies, resulting in maternal and perinatal morbidity and mortality. Imbalances in milieu of serum sodium and potassium, that are involved in functioning of vascular smooth muscles, leads to vasoconstriction and hypertension in PE. Calcium deficiency stimulates parathyroid hormone, leading to vasoconstriction. Magnesium regulates blood pressure by monitoring vascular tone and structure. There is scarcity of studies on these factors in PE in central Karnataka. To estimate levels of serum calcium, magnesium, sodium and potassium in preeclampsia. Hospital based cross-sectional study conducted from September, 2020 to February, 2021 at a Tertiary Teaching Hospital in Chitradurga. 60 diagnosed cases of preeclampsia and equal number of age, parity and gestational age matched women with singleton normal pregnancies, attending antenatal clinic or admitted and treated in obstetrics wards of the hospital were included in the study. Clinical examination and laboratory investigations to estimate biochemical parameters were conducted. Data was analyzed in SPSS V:20. Statistical tests like chi-square and One-way ANOVA test were applied to find the significance of associations. Hypernatremia, hypokalemia, hypomagnesemia and hypocalcemia were significant in preeclampsia compared to normal pregnancy group. In severe preeclamptia, highest levels of serum sodium and lowest levels of serum potassium, magnesium and calcium were found compared to the mild PE group. Timely estimation of serum electrolytes, calcium and magnesium through the course of pregnancy could help in early detection and prompt treatment of preeclampsia and also can prevent the adverse outcomes of pregnancies. Also, dietary restriction of sodium and dietary supplementation of calcium, magnesium and potassium rich foods to the pregnant women and calcium supplementation could reduce the risk of preeclampsia.

The metabolic landscape of decidua in recurrent pregnancy loss using a global metabolomics approach

IntroductionMaternal metabolism undergoes dynamic changes during pregnancy. A deviation from this physiological metabolic status might be involved in the pathogenesis of pregnancy complications, such as recurrent pregnancy loss (RPL). Decidua is an important uterine tissue, which provides immunological protection as well as nutritional support to the developing embryo during early pregnancy. Previous studies have shown that aberrant metabolism of the decidua is related to the etiology of RPL. However, the metabolic profile of the decidua in RPL has not yet been fully elucidated. MethodsIn the current study, decidual samples from RPL patients (n = 23) and normal pregnancy (NP) women (n = 30) were collected, and hydrophilic and hydrophobic metabolites were extracted and measured using a liquid chromatography electrospray ionization tandem mass spectrometry system. Besides, the mRNA expression of several critical enzymes involved in sphingolipid metabolism and glycerophospholipid metabolism was detected. ResultsThe OSC-PLS-DA scores plot illustrates that metabolic differences are present in the decidual tissue of RPL patients compared with that of NP women. Combining multivariate analysis with univariate statistical analysis, a total of 62 metabolites related to RPL were selected, including carnitine, glycerophospholipids, sphingomyelin (SM), ceramide, organic acids and their derivatives, and amino acid metabolomics. KEGG analysis showed that abnormalities in multiple metabolic pathways occurred in RPL decidua, including vitamin digestion and absorption, tryptophan metabolism, citrate cycle, arginine biosynthesis, glycerophospholipid metabolism, sphingolipid metabolism, and sphingolipid signaling pathway. Increased SM synthase and decreased Phospholipase A2 Group IIE mRNA levels were detected in RPL compared with NP group. DiscussionDisruption of decidual metabolism, especially glycerophospholipid metabolism and sphingolipid metabolism, might be involved in the occurrence of RPL.

HMGB1 regulates lipopolysaccharide-induced cellular dysfunction in HTR8/SVneo cells: Implications for the role of HMGB1 in unexplained spontaneous miscarriage

IntroductionApproximately half of miscarriages are of an unknown aetiology and are likely characterized by aberrant inflammation at the uteroplacental interface. High mobility group box 1 (HMGB1) is a ubiquitous nuclear protein that participates in the pathological inflammatory response. The present study investigated the role of HMGB1 in inflammation-induced damage in trophoblasts and elucidated the underlying mechanism. MethodsImmunohistochemistry, qRT-PCR and Western blotting were used to detect the expression of HMGB1 in early unexplained miscarriage and normal placentas. Lipopolysaccharide (LPS)-induced HTR8/SVneo cells were used as an in vitro model to mimic the aberrant inflammation at the uteroplacental interface of miscarriage. The expression of HMGB1 and the autophagy-related proteins LC3 and Beclin1 was detected using Western blotting. Autophagy was studied in villous tissues using immunofluorescence and Western blotting. Cell proliferation and migration were analysed. ResultsThe expression level of HMGB1 in villous tissues with early unexplained miscarriage was significantly higher than the normal pregnancy group. The inhibition of HMGB1 in LPS-treated HTR8/SVneo cells decreased the expression of Beclin 1 and LC3, which promoted cell proliferation and migration. We found a high level of autophagy in miscarriage placentas. HMGB1 and autophagy inhibition reversed the proliferation and migration of LPS-induced HTR-8/SVneo cells. DiscussionOur results demonstrated that HMGB1 participated in LPS-induced inflammation via autophagy and regulated trophoblast functions, such as cell proliferation and migration, to potentially participate in the pathogenesis of miscarriage.

Aberrant Level of Estrogen Correlates with Defective Thrombopoiesis during Pregnancy in Patients with Immune Thrombocytopenia

AbstractPregnancy seems to be a high-risk event in immune thrombocytopenia(ITP)because disease flares are frequently observed during gestation clinically, and the treatment with glucocorticoid is often ineffective. Sex hormones are changed dramatically during pregnancy to maintain a stable environment both for the mother and for the fetus. To determine the sex hormone levels during pregnancy in ITP, sex hormones were analyzed in patients with ITP and matched healthy women before, during, and after pregnancy. We demonstrated that there is a relationship between estrogen level and thrombopoiesis in ITP pregnancy. Moreover, we showed that estrogen plays a role in glucocorticoid resistance which is common in ITP patients who are pregnant.Thirty consecutive successful pregnancies in 30 patients with ITP, 21 pregnancies in 21 healthy controls, twenty patients with primary ITP and 19 healthy subjects were studied. Serum samples for sex hormone testing, including estrogen, progesterone, testosterone, prolactin, LH and FSH, were collected and analyzed. We confirmed that serum levels of all sex hormones varied significantly during pregnancy and postpartum, both in the patients with ITP and in healthy controls, as expected. However, the concentration of estrogen was significantly lower in pregnant ITP patients, compared with healthy pregnant subjects, leading to a completely different profile.To clarify whether the different estrogen concentration has a direct effect on megakaryocyte(MK) maturation and thrombopoiesis during pregnancy in ITP, BM-derived CD34+ cells from ITP patients and healthy controls in pregnancy, were treated with different doses of estrogen. We found that estrogen had the ability to promote MK polyploidization, maturation and proplatelet formation via estrogen receptor(ER) in healthy controls, but the concentration of estrogen, which was lower than that of the normal-pregnancy group, could not play the above role in CD34+ cells of pregnancy-ITP group. To determine the differences in MKs treated with estrogen of different doses in each group, we screened some essential transcription factors that may participate in the regulation of MK polyploidization and maturation. The expression levels of GATA1, FLI1, FOG-1, KLF-1, and NF-E2, were detected by RT-PCR and Western blot. We found that, in the pregnancy-ITP group treated with lower estrogen, the expression of GATA1 and NF-E2 was significantly reduced compared with the healthy control. We obtained similar results with the bone marrow samples, indicating that pregnant ITP patients showed more obvious detects in megakaryocyte maturation defect and lower expression of transcription factors. Further investigation is needed to evaluate the expression of ER and its nuclear translocation in MKs of the pregnancy-ITP group treated with the relatively lower level of estrogen.We also explored if the relatively reduced estrogen level plays a role in glucocorticoid resistance which is commonly observed in ITP patients during pregnancy. We evaluated the inhibitory effects of dexamethasone, with or without different concentrations of estrogen, on the proliferation of PBMCs from the pregnancy-ITP group induced by a mitogen. We found that estrogen impaired the inhibitory effects of dexamethasone. Further study with immunofluorescence demonstrated that estrogen upregulated the expression of protein phosphatase, which affected the glucocorticoid receptor activation.In conclusion, an unexpected lack of estrogen serum level increase occurs in patients with ITP during pregnancy. The relatively reduced level of estrogen cannot induce the expression of GATA1 and NF-E2 via ER in pregnant ITP patients, which is required for MK maturation and thrombopoiesis. Meanwhile, setrogen inhibits glucocorticoid action via protein phosphatase, which may account for the glucocorticoid resistance observed in pregnant ITP patients. DisclosuresNo relevant conflicts of interest to declare.