Normal Pregnant Controls Research Articles

Vitamin D Supplementation Reduces Serum Chemerin Level in Gestational Diabetes Mellitus Rat Model

AbstractBackground: Gestational Diabetes Mellitus (GDM) is the most common metabolic disorder that increases the prenatal morbidity. Data regarding the association between circulating chemerin level and GDM remains controversial. On the other hand, Vitamin D deficiency is common in pregnancy and may increase the frequency of GDM.Aim of Study: This study was conducted to examine the effects of Vitamin D3 supplementation on serum chemerin level and some metabolic parameters in GDM rat model.Material and Methods: Healthy female white albino rats were divided randomly into three groups (n=10 rats): Group I (normal pregnant group); fed on normal diet for five weeks before induction of pregnancy. Group II (GDM-induced); fed High Fat-Sucrose Diet (HFSD) for five weeks before induction of pregnancy then injected Intraperitoneally (I.P) by Strepto-zotocin (STZ) (25mg/kg) on the 7th day of gestation. Group III (GDM-induced group supplemented with Vitamin D3); GDM-induced as before and injected Intramuscularly (I.M) with 20,000IU/kg of cholecalciferol on days 1 and 14 of gestation. On the 19th day of gestation, serum chemerin, estradiol, progesterone, glucose, insulin and Insulin Resistance index (HOMA-IR), Total Cholesterol (TC), Triglycerides (TG), Low Density Lipoprotein-cholesterol (LDL-c), High Density Lipoprotein-cholesterol (HDL-c), Very Low Density Lipoprotein-cholesterol (VLDL-c), Tumor Necrosis Factor alpha (TNF a) and Malondialdehyde (MDA) levels and Serum Superoxide Dismutase (SOD) activity were estimated for all groups.Results: GDM-induced rats showed significantly increased serum glucose, HOMA-IR, TG, TC, LDL-c, VLDL-c, MDA, and TNF a levels while showed significantly decreased serum insulin and HDL-c levels and SOD activity when compared to normal pregnant control rats. GDM-induced rats also showed significantly increased serum chemerin levels that showed significant positive correlations with serum glucose, insulin, HOMA-IR, TG, TC, LDL-c, VLDL-c, MDA, and TNF a levels but showed significant negative correlations with serum HDL-c level and SOD activity. Noteworthy, Vitamin D3 administration significantly improved these pa-rameters in GDM-induced group supplemented with Vitamin D3.Conclusion: Our results denoted the protective effect of Vitamin D3 supplementation on GDM that may be through improving the antioxidant and inflammatory status. Decreasing circulating chemerin level may play a role in this protective effect.

Correlation analysis between COX-2 gene polymorphism and eclampsia.

The aim of this study was to investigate the expression of cyclooxygenase-2 (COX-2) in eclampsia patients, and to explore the correlation between COX-2 polymorphism and incidence of eclampsia. From January 2016 to January 2018, a total of 280 pregnant women diagnosed in the Obstetrics and Gynecology Department of our hospital were selected for this study. All patients were divided into two groups, including normal pregnancy control group (n=120) and eclampsia group (n=160). The expression of COX-2 in placenta and umbilical cord tissues of eclampsia group and normal group was detected via Reverse Transcription-Polymerase Chain Reaction (RT-PCR), Western blotting and immunohistochemical staining. The single-nucleotide polymorphisms (rs1526172, rs1245231 and rs2198532) in the promoter region of the COX-2 gene were typed via conformation difference gel electrophoresis. Whether the distribution frequency of COX-2 genotypes met Hardy-Weinberg equilibrium law was detected via the Chi-square test. Meanwhile, the correlation between COX-2 alleles and gene polymorphisms and the incidence of eclampsia was analyzed. The messenger ribonucleic acid (mRNA) and protein expression levels of COX-2 in the eclampsia group were significantly higher than those of the normal group (p<0.05). According to the analysis, three polymorphisms of COX-2 gene were all in line with Hardy-Weinberg equilibrium distribution (p>0.05). Gene association analysis revealed that only polymorphisms (rs1526172 and rs1245231) and alleles were correlated with the incidence of eclampsia (p<0.05). However, polymorphism rs2198532 and alleles were not correlated with the incidence of eclampsia (p>0.05). Rs1526172 and rs1245231 in the promoter region of COX-2 are correlated with the incidence of eclampsia, while rs2198532 has no correlation with eclampsia.

Hypertension Editors' Picks Preeclampsia.

Hypertension Editors' Picks Preeclampsia.

Serum ischemia modified albumin as a potent biochemical marker in pre-eclampsia patients attending a tertiary care hospital in central India

Serum ischemia modified albumin as a potent biochemical marker in pre-eclampsia patients attending a tertiary care hospital in central India - IJCBR- Print ISSN No: - 2394-6369 Online ISSN No:- 2394-6377 Article DOI No:- 10.18231/j.ijcbr.2019.046, International Journal of Clinical Biochemistry and Research-Int J Clin B

Higher ꞵ-human chorionic gonadotropin and estrogen levels during the first 6 weeks of pregnancy are associated with threatened abortion.

The associations of human chorionic gonadotropin (hCG), estrogen, and progesterone levels with threatened abortion have not been fully studied. Eighty women with threatened abortion were recruited sequentially, and the levels in their pregnancy hormones during the first trimester were compared with that of 160 normal early pregnancy controls. The natural logarithm transformed (Ln) hCG and Lnestrogen of women with threatened abortion and gestational age ≤ 6 weeks were significantly higher than values for the normal controls of the same gestational age (8.6 ± 1.2 vs. 7.4 ± 1.7 mIU/mL and 5.8 ± 0.4 vs. 5.4 ± 0.5 pg/mL); the two hormones reached similar levels in the groups of gestational age > 6 weeks. Among the group with gestational age ≤ 6 weeks, a univariate logistic regression showed that LnhCG and Lnestrogen were associated with threatened abortion, with odds ratios (ORs) of 1.85 [95% confidence interval (CI): 1.30-2.64] and 4.62 (95% CI: 1.67-12.80), respectively. The multivariate logistic regression model revealed that hCG and estrogen were mutually confounding factors, and only hCG was an independent factor for threatened abortion (OR 1.56; 95% CI: 1.06-2.28). None of the variables in the univariate or multivariate logistic regression was a factor associated with threatened abortion after 6 weeks gestational age. In conclusion, β-hCG and estrogen levels in the first half of the first trimester are factors associated with threatened abortion.

Curcumin Does Not Attenuate the Preeclamptic Phenotype in the Dahl Salt‐Sensitive Rat

Preeclampsia (PE) is associated with new onset of hypertension and proteinuria and affects 2–8% of pregnancies worldwide. It is a leading cause of maternal and fetal morbidity and mortality with no current therapy to manage the disease. While its etiology is yet to be elucidated, immune system activation of various inflammatory pathways is reported to be a contributing factor. Toll‐like receptor (TLR) activation by damage‐associated molecular patterns (DAMPS) released following poor placentation and oxidative stress has been linked to the development of PE and TLR4 expression is increased in the placenta of preeclamptic women. We performed a whole transcriptomic analysis on placental tissues from gestation day (GD) 14 rats using Affymetrix Rat 2.0ST GeneChip and noted significant dysregulation in multiple genes during pregnancy in the Dahl salt sensitive (S) rat, a model of spontaneous superimposed preeclampsia, compared to the normal pregnant control Sprague Dawley (SD) rat. These genes included upregulation of TLR4 in the placenta of Dahl S rats (1.9 fold, p&lt;0.05), which was subsequently confirmed via quantitative real‐time PCR (2.9 fold, p&lt;0.05). To further investigate this pathway, the goal of this study was to assess the effect of TLR4 inhibition in pregnant Dahl S rats. Curcumin, the anti‐oxidant and anti‐inflammatory active ingredient in the spice turmeric, has been reported to inhibit TLR4 activation, and reduced blood pressure in rodent models of LPS‐induced preeclampsia. We hypothesized that curcumin would inhibit TLR4 activation and reduce blood pressure and uterine artery resistance index during pregnancy in the Dahl S rat. Starting on gestational day (GD) 10, 17 weeks old rats were divided into two groups: a treated group (N=7) that orally received dough containing 400mg/kg of curcumin daily and a control group (N=6) that received the vehicle dough through GD20. On GD18, Uterine Artery Resistance Index (UARI) was measured via Doppler ultrasound. On GD20, terminal blood pressure measurements were taken, and pups and placentas harvested and measured. Curcumin had no effect on UARI (0.78 vs. 0.82, p=0.4) or mean arterial pressure (146 ± 5 vs. 133 ± 5 mmHg, p=0.08). Fetal outcome assessed by litter size (10 ± 1 vs. 11 ± 1 pups); pup weight (2.23 ± 0.08 vs. 2.30 ± 0.07 g) and pup length (29.44 ± 0.31 vs. 29.6 ± 0.46 cm) was similar between groups. These results suggest that administration of curcumin does not alleviate the preeclamptic phenotype in the Dahl S rat.Support or Funding InformationR01HL1347111R01HL137673This abstract is from the Experimental Biology 2019 Meeting. There is no full text article associated with this abstract published in The FASEB Journal.

Acute Kidney Injury during pregnancy decreases pup size and sensorimotor development

BACKGROUNDAcute kidney injury during pregnancy (NP+AKI) leads to growth restriction and a delay in neurodevelopment in the resulting babies. As the incidence of AKI during pregnancy has been increasing over the last few years it is important to examine the consequences of this disorder during pregnancy. We hypothesize that similar to what is seen in humans with intrauterine growth restriction, there will be a sex difference in sensorimotor development between NP and NP+AKI rat pups.METHODSTo induce AKI, on gestational day (GD) 18, normal pregnant (NP) rats (n=4) had their renal pedicles isolated and occluded with microvascular clamps for 45 minutes under anesthesia. NP control rats (n=4) that received no surgical interventions served as controls and all rats delivered on GD21. 2–3 pups/litter were placed with a separate set of SHAM rats. Beginning on postnatal day (PND) 4 rat pups underwent the standard Irwin battery of developmental milestones: Surface righting, negative geotaxis, cliff avoidance, open circle. All pups were sexed and euthanized between PND32‐35.RESULTSRat pups born to NP+AKI dams weighed significantly less compared to NP pups (p&lt;0.0001). AKI pups were significantly smaller compared to NP pups (p&lt;0.0001). This trend remained true for female AKI pups through PND9 (p&lt;0.05); after which time both NP and NP+AKI females were significantly smaller than male pups. On PND3 NP+AKI females took longer to complete surface righting (23.5±12.7sec) compared to rat pups in the groups. Similar results were seen in cliff avoidance between groups (30.5±16.5 vs. 48.7±11.3sec; respectively). On PND5 NP+AKI pups (55.7±4.3sec) take longer to complete the negative geotaxis task compared to NP pups (17±1sec). There was a statistically significant difference in kidney size between female and male NP rats (p=0.02). There was not a statistically significant sex differences between groups in brain size (p=0.06), however NP+AKI pups had significantly smaller brains compared to NP pups (p=0.03).CONCLUSIONNP+AKI pups are smaller compared to NP pups and have delays in surface righting. AKI during pregnancy did not affect kidney size in offspring, however both male and female NP+AKI pups had smaller brains more than 30 days post‐birth compared to NP pups. The results from this study suggest that AKI during pregnancy leads to a significant delay in growth and sensorimotor development.Support or Funding InformationResearch reported in this publication was supported by the National Institute Of General Medical Sciences of the National Institutes of Health under Award Number P20GM121334. The content is solely the responsibility of the authors and does not necessarily represent the official views of the National Institutes of Health.This abstract is from the Experimental Biology 2019 Meeting. There is no full text article associated with this abstract published in The FASEB Journal.

Ambient PM2.5 and clinically recognized early pregnancy loss: A case-control study with spatiotemporal exposure predictions

BackgroundExperimental research suggests that fine particulate matter (PM2.5) exposure might affect embryonic development. However, only few population-based studies have investigated the impact of maternal exposure to PM2.5 on the early pregnancy loss. ObjectivesTo estimate associations between clinically recognized early pregnancy loss (CREPL) and exposure to ambient PM2.5 at individual residences during peri-conception periods, with the aim to identify susceptible exposure time windows. MethodsCREPL cases and normal early pregnancy controls (of similar age and gravidity presenting within one week, a total of 364 pairs) were recruited between July 2017 and July 2018 among women residing in Tianjin, China. Average ambient PM2.5 concentrations of ten exposure windows (4 weeks, 2 weeks and 1 week before conception; the first, second, third and fourth single week, the first and second 2-week periods, and the entire 4-week period after conception) at the women's residential addresses were estimated using temporally-adjusted land use regression models. Associations between PM2.5 exposures at specific peri-conception time windows and CREPL were examined using conditional logistic regression models, adjusted for covariates. ResultsBased on adjusted models, CREPL was significantly associated with a 10 μg/m3 increase in PM2.5 exposure during the second week after conception (OR = 1.15; 95% CI: 1.04, 1.27; p = 0.005), independent of effects at other time windows. There was also an association of CREPL with PM2.5 during the entire 4-week period after conception (OR = 1.22; 95% CI: 1.02, 1.46; p = 0.027). There was little evidence for associations with exposure during pre-conception exposure windows. ConclusionsMaternal exposures to ambient PM2.5 during a critical time window following conception are associated with CREPL, with the second week after conception possibly being the exposure window of most vulnerability. Future studies should focus on replicating these findings and on pathogenic mechanisms.

Association of imbalanced sex hormone production with excessive procoagulation factor SerpinF2 in preeclampsia.

Preeclampsia, a serious pregnancy-associated syndrome, is the leading cause of maternal and perinatal morbidity and mortality. Significant exacerbation of the hypercoagulation status as well as imbalanced steroid hormones have been reported in developed preeclampsia. However, it remains unclear whether the two pathological changes are directly associated. Our proteomic analysis revealed a significantly elevated SerpinF2/α2-antiplasmin level in preeclampsia plasma. Measurement of the longitudinally gestational change of plasmin-α2-antiplasmin (PAP) complex, testosterone, estradiol in preeclampsia patients and normal pregnant women demonstrated that the circulating PAP and testosterone levels in the early-onset preeclampsia (E-PE) patients were substantially higher, whereas estradiol concentration was significantly lower than that in normal pregnant controls from early pregnancy throughout gestation. Correlation analysis revealed that circulating PAP is in positive correlation with the concentration of testosterone, and in negative correlation with estradiol in E-PE patients. In E-PE placenta, the productions and activities of 17β-hydroxysteroid dehydrogenases 3 and aromatase, the essential enzymes for testosterone and estradiol synthesis, were compromised. In human renal and trophoblastic cells, testosterone and estradiol could regulate SerpinF2 expression in opposite ways. In addition, obvious fibrin deposition was colocalized with SerpinF2 in intervillous spaces and the area surrounding syncytiotrophoblasts in E-PE placenta. The findings reveal a tight correlation between the imbalanced steroid hormone production and the procoagulation factor in E-PE patients, which provide potential biomarkers to predict preeclampsia, and bring new insight into the pathogenesis of preeclampsia.

Pregnancy Specific Beta-1 Glycoprotein, Pro- and Anti-inflammatory Cytokines in Eclampsia in Kaduna State, Nigeria

Eclampsia (EC), a human pregnancy–specific-syndrome is the life-threatening occurrence of convulsion (s) in association with signs of preeclampsia (hypertension and proteinura). Eclampsia has remained a significant public health threat, contributing to maternal and prerinatal morbidity and mortality in Nigeria. However, the pathogenic mechanism of the disease is not fully understood. Disturbance of the cytokine equilibrium has been accused for many pathological disorders including EC. Thus the aim of this study was to analyze the maternal cytokines and pregnancy specific beta-1 glycoprotein in EC and compared results with those of normal healthy pregnant controls. Enzyme linkedimmunosorbent assay (ELISA) was used to measure levels ofpro-inflammatory cytokines (Tumor necrosis [TNF]-α, and interleukin [IL] -2), anti-inflammatory cytokines [IL-4 and IL-10] and pregnancy specific beta-1 glycoprotein (PSG-1) in the peripheral blood of patients with EC (n=38), normal healthy pregnant women [PC] (n=25) and compared withhealthy non pregnant women controls [NPC] (n=25). Women with malaria and human immunodeficiency virus infections were excluded from the study. The overall results (Mean ±SD) were: TNF-α (2.34 ±0.13 pg/ml) in EC was significantly higher than the mean values (2.25±0.07pg/ml and 2.24±0.10 pg/ml) in PC and NPC respectively. Furthermore, EC had higher TNF-α mean value compared with NPC (P<0.05). There was no statistical difference in mean IL-2 value between EC (1.69±0.17 Pg/ml), PC (1.71±0.0.09Pg/ml) and NPC (1.72±0.13Pg/ml) (P>0.05). The mean value of IL-10 was noted to be lower in EC (1.28±0.54Pg/ml) compared with: PC (1.58±0.61 Pg/ml) and NPC (2.06±0.08Pg/ml). No significant difference in IL-4 mean value exist between EC (2.45±0.10 Pg/ml) and NPC (2.45 Pg/ml) (P>0.05) but significant difference exist between EC and NPC (2.40±0.0 6Pg/ml) (P<0.05). The serum PSG-1 levels in EC (2.5±0.11 Pg/ml) and PC (2.5±0.03 Pg/ml) were similar and significantly higher than in NPC (0.06±0.020 Pg/ml) P<0.05. While a pro-inflammatory cytokine environment was demonstrated in EC, and decreased anti-inflammatory reactivity, EC was not associated with low levels of PSG-1. Further research is advocated to discover how anti-inflammatory cytokines could be exploited as a therapeutic agent for women at high risk of EC.

Clinical application evaluation of serum C1q and other complement factors in the diagnosis and prediction of preeclampsia

Objective To observe the levels of serum complement C1q, C3, C4 and factor B in different phases during normal pregnancy; To evaluate the diagnostic value and the predictive value of serum complement C1q, C3, C4 and factor B in preeclampsia (PE). Methods Three groups of subjectes were enrolled from January 2017 to March 2018 in Department of Obstetrics and Gynecology, Peking University Third Hospital. (1) 30 pregnant women in each group at 8-14 weeks, 20-26 weeks and 28-36 weeks were retrospectively selected, and the serum levels of complement C1q, C3, C4 and B factors were measured and compared. (2)Selecting 17 cases of early-onset mild PE, 47 cases of early-onset severe PE, 24 cases of late-onset mild PE, 27 cases of late-onset severe PE, and 30 normal pregnant cases of the same gestational stage as early-onset / late-onset controls, through ANOVA analysis and comparison between two groups, this study evaluated the diagnostic value of serum complement C1q, C3, C4 and factor B in PE. (3)To evaluate the predictive effect in PE, it analyzed serum C1q and factor B levels of pregnant women at 20-26 gestation weeks through prospective nested case-control study of 214 cases. Results The levels of serum C1q remained stable in the whole pregnancy. The levels of C3 and factor B increased at the early stage of pregnancy and remained stable after the middle stage. C4 increased early in pregnancy and then remained stable. Compared with the control group, the levels of serum C1q in all four types of PE patients were significantly decreased (median: 169 mg/L, 161 mg/L, 165 mg/L, 163 mg/L; early-onset, late-onset control group: 187 mg/L, 194 mg/L; U=130.500, 426.500, 159.500, 130.500, all P 0.05). 33 (15.4%) cases developed PE out of 214 pregnant women with PE risk factors. Compared to those who didn′t develop PE, it showed no statistical difference of serum C1q, C3, C4, and factor B levels at 20-26 gestational weeks of the women who subsequently developed PE (C1q: 175 mg/L vs. 184 mg/L; C3: 1 523 mg/L vs. 1 467 mg/L; C4: 230 mg/L vs. 229 mg/L; FB: 344 mg/L vs. 320 mg/L; U=2 090.000, 1 575.000, 2 058.500, 1 362.000, all P>0.05). Compared to those of the healthy pregnant controls, it showed no statistical difference of serum C1q, C3 and C4 levels of 20-26 gestational weeks of the women who subsequently developed PE (C1q: 175 mg/L vs. 190 mg/L; C3: 1 523 mg/L vs. 1 428 mg/L; C4: 230 mg/L vs. 227 mg/L; U=353.000, 395.000, 493.500, all P>0.05), while it showed statistical difference (344 mg/L vs. 306 mg/L; U= 233.500, P=0.007) for factor B. Conclusions Serum C1q level of PE patients significantly decreased, which can be used as potential indicators of PE diagnosis, but serum C1q, C3, C4 level of 20-26 gestational weeks cannot predict risk of PE. Factor B cannot serve as serum index of PE diagnosis, but its serum levels at 20-26 gestational weeks werer higher than those of normal pregnant controls, factor B may be a potential predictor, but need further verification. (Chin J Lab Med, 2018, 41: 934-942) Key words: Preeclampsia; Complement; C1q; C3; C4; factor B

Comparison of The Therapeutic Effect of Syngeneic, Allogeneic, and Xenogeneic Adipose Tissue-Derived Mesenchymal Stem Cells on Abortion Rates in A Mouse Model.

Objective Mesenchymal stem cells (MSCs), due to their immunomodulatory functions, are an ideal candidate for the treatment of immune-related diseases. Recurrent spontaneous abortion (RSA) is one of the most common complications of pregnancy which in many cases is related to the immune system disorders. Our previous study has shown that the abortion rate was decreased following the syngeneic MSCs therapy in abortion-prone mice. In this study, the therapeutic effect of syngeneic, allogeneic, and xenogeneic MSCs was compared in a mouse model of RSA. Materials and Methods In this experimental study, MSCs were isolated from adipose tissue (ASCs) of CBA/J and BALB/c mice and human. After characterization, ASCs were injected (IP) at day 4 of gestation to female CBA/J mice following their mating with DBA/2 male mice. In the control group, phosphate-buffered saline (PBS) was injected and CBA/J×BALB/c mating was also used as the normal pregnancy control. On day 14.5 of pregnancy, embryo resorption rate was determined. Results The abortion rate significantly decreased following the ASCs therapy from syngeneic (6.31%), allogeneic (6.54%), and xenogeneic group (12.36%) compared to ASCs non-treated group (34.4%). There was no statistical difference between ASCs treated groups, however syngeneic and allogeneic ASCs reduced the abortion rate more efficiently than xenogeneic ASC. ConclusionThe abortion rate was significantly decreased following the intraperitoneal administration of ASCs from various donated sources in abortion-prone mice. These results indicated that the immunogenicity of allogeneic and xenogeneic ASCs is not a contradictory problem for their therapeutic effects on RSA.

Increased apoptosis of trophoblasts from pregnancies complicated by intrauterine growth restriction is associated with aberrant Fas-associated death domain (FADD) expression

Intrauterine growth restriction (IUGR) is one of the most common pregnancy complications worldwide. However, the pathogenesis of IUGR is not completely clear. The authors conducted this study to investigate trophoblast apoptosis and the underlying molecular mechanisms in fetal membranes from pregnancies complicated by IUGR, in order to further understand the potential pathological processes involved in human IUGR. Fetal membranes were obtained from patients with pregnancies affected by IUGR (n = 10) and normal term pregnancies (n = 10). Nine of the ten delivered infants had a birth weight below the 10th percentile for gestational age, accompanied by morphological differences, and other extensive lesions common in IUGR cases. The fetal membranes were subjected to enzymatic digestion and flow cytometric analysis to evaluate apoptosis, as well as determination of cleaved caspase-3 and poly (ADPribose) polymerase (PARP) products. Expression of Fas-associated death domain (FADD) protein was detected using Western blot. Increased apoptosis was observed in the trophoblasts of fetal membranes from IUGR cases compared with normal control pregnancies. Trophoblasts from the fetal membranes of IUGR pregnancies exhibited consistently increased expression of the FADD protein compared to those from the normal pregnancies. The present results revealed significantly enhanced apoptosis and aberrant FADD expression in the trophoblasts from fetal membranes obtained from pregnancies complicated by IUGR compared with normal pregnancies. The disrupted balance of trophoblast apoptosis may be associated with aberrant FADD expression, which contributes to the pathological processes associated with IUGR.

Hypertension, Anxiety, and Blood-Brain Barrier Permeability Are Increased in Postpartum Severe Preeclampsia/Hemolysis, Elevated Liver Enzymes, and Low Platelet Count Syndrome Rats.

Hypertension and inflammation during pregnancy are suggested to contribute to the development of postpartum depression and anxiety. Using a rat model of severe preeclampsia and hemolysis, elevated liver enzymes, and low platelet count syndrome, which displays both hypertension and inflammation during pregnancy, we evaluated whether rats were prone to develop depression or anxiety in the postpartum period. On gestational day 12, miniosmotic pumps infusing sFlt-1 (soluble fms-like tyrosine kinase-1) and sEng (soluble endoglin) were placed into rats, a subset of these rats was infused with 2 mg/kg of Orencia (abatacept) the following day to determine whether immune suppression via T-cell depletion prevented any changes in maternal depression or anxiety-like behavior. All rats, including normal pregnant (NP) controls, delivered between gestational days 21 and 22. Postpartum severe preeclamptic rats buried significantly more marbles compared with NP rats ( P=0.002) and Orencia-treated rats ( P=0.05). Severe preeclamptic rats spent significantly more time in closed arms of the elevated plus maze compared with NP rats ( P=0.009) and Orencia-treated rats ( P=0.05). Severe preeclamptic rats were hypertensive compared with NP ( P=0.03) and Orencia-treated rats ( P=0.01). Finally, severe preeclamptic rats had increased blood-brain barrier permeability compared with NP rats ( P=0.03), which was reversed in Orencia-treated rats ( P=0.008). These results suggest that severe preeclampsia/hemolysis, elevated liver enzymes, and low platelet count syndrome during pregnancy contributes to an increase in anxiety-like behavior, blood-brain barrier permeability, and hypertension in the postpartum. The current results suggest that T-cell suppression during pregnancy can also help prevent chronic hypertension and increased anxiety in the postpartum period.

Evaluation of diastolic left ventricular energy loss in patients with pregnancy-induced hypertension using vector flow mapping

Objective To quantify the diastolic average energy loss (EL) of left ventricle in patients with pregnancy-induced hypertension (PIH) by vector flow mapping (VFM) technique and explore the clinical significance of EL in evaluating left ventricular diastolic function in patients with PIH. Methods Fifty-seven cases of singletonic PIH in late pregnancy (PIH group) and 38 cases of the third trimester normal singleton pregnancy (control group) were enrolled in this study. VFM were used to analyze the total average energy loss (ELt) and average energy loss at the basal level (ELb), the papillary muscle level (ELp), and the apical level (ELa) in isovolumic relaxation, rapid filling, mid-diastol and atrial systole phases, and the differences between the two groups were compared. The correlation between ELt and E/e in both groups were analyzed. Results In PIH group, ELt, ELb, ELp and ELa in the mid-diastolic and atrial systolic phases were significantly higher than those in control group (all P<0.01); ELt, ELp, ELa in isovolumic diastolic phase and ELt, ELb and ELa in fast filling phase were higher than those in control group (all P<0.05). There was a positive correlation between ELt and E/e in isovolumic diastolic phase, rapid filling phase and atrial systolic phase in PIH group (r=0.326, 0.386, 0.403; all P<0.05). There was a positive correlation between the ELt of fast filling and atrial systolic phases and E/e in control group (r=0.498, 0.371; all P<0.05). Conclusions Increased left ventricular diastolic flow EL in PIH patients reflects the abnormal intraventricular hemodynamic changes, and it is related to left ventricular diastolic function parameters for the quantitatively evaluation of PIH patients, and might be feasible to reveal the extent and mechanism of left ventricular diastolic dysfunction. Key words: Vector flow mapping; Pregnancy-induced hypertension; Ventricular function, left; Energy loss

Dysfunction of pseudogene PGK1P2 is involved in preeclampsia by acting as a competing endogenous RNA of PGK1.

Normal decidualization is essential for normal pregnancy and abnormal decidualization is thought to cause preeclampsia (PE). Phosphoglycerate kinase 1 (PGK1) is an enzyme involved in the glycolytic pathway which is the main metabolism process decidual cells exhibit. Phosphoglycerate kinase 1, pseudogene 2 (PGK1P2), which is also a long non-coding RNA (lncRNA), has a high sequence similarity to PGK1 and therefore acquires an ability for sequence-specific regulation. The expression of PGK1 and PGK1P2 in human decidua, as well as their relationship and functions during decidualization was investigated using in vitro cultured human endometrial stromal cell lines (hESCs) and primary ESCs by real-time PCR, immunohistochemistry, western blotting, siRNA techniques and miRNA inhibitor or mimic transfection. The levels of PGK1 and PGK1P2 mRNA and PGK1 protein in severe preeclamptic decidua were lower than those in normal pregnant controls. PGK1 and PGK1P2 mRNAs were both induced after in vitro decidualization and their deficiency caused impaired decidualization in turn. We also found PGK1P2 acted as a competing endogenous RNA (ceRNA) to regulate PGK1 expression through miR-330-5p. We proved that PGK1 and PGK1P2 are a pair of ceRNAs against miR-330-5p and they play a vital role in human decidualization by regulating angiogenesis and glycolysis metabolism. The deficiency of PGK1 and PGK1P2 in the decidua jeopardizes the decidualization process and subsequently might lead to the occurrence of PE. These findings may help in promoting novel predictive, diagnostic and prognostic biomarkers of PE in future.

Progesterone Effects on Vaginal Cytokines in Women with a History of Preterm Birth [15E

INTRODUCTION: To evaluate the vaginal immune response of intramuscular progesterone supplementation in pregnant women at risk for preterm birth compared to normal healthy pregnant controls. METHODS: A prospective, cohort study from June 2016 to August 2017 included women at a gestational age 11-16 weeks, &gt;18 years of age, and a singleton pregnancy after IRB approval. Women in the progesterone arm had a history of preterm birth and received intramuscular 17-hydroxyprogesterone caproate. Controls were comprised of healthy, uncomplicated pregnancies. Exclusion criteria were vaginitis, diabetes mellitus, hypertension, and other chronic diseases affecting the immune response. A vaginal wash was performed on entry to the study, at 26 to 28 weeks, and at 35-36 weeks. Samples underwent semi-quantitative detection of human inflammatory markers. Immunofluorescence pixel density data was analyzed and P value &lt;0.05 was considered significant. RESULTS: There were 39 women included, 10 with a prior preterm birth and 29 controls. The baseline demographics and pregnancy outcomes for both groups were similar in age, parity, race, BMI, gestational age at delivery, mode of delivery, and birth weight. Enrollment cytokines in women with a prior preterm birth, including IL-1 alpha (39.2+25.1% versus 26.1+13.2%; P=0.04), IL-1 beta (47.9+26.4% versus 24.9+17%; P&lt;0.01), IL-2 (16.7+9.3% versus 11.3+6.3%; P=0.03), and IL-13 (16.9+12.4% versus 8.2+7.4%; P=0.01), were significantly elevated compared with controls. In the third trimester the cytokine densities for IL-1 alpha (26.0+18.2% versus 22.3+12.0%; P=0.49), IL-1 beta (31.8+15.9% versus 33.1+16.8%; P=0.84), IL-2 (10.0+8.4% versus 10.9+5.9%; P=0.71), and IL-13 (9.1+5.9% versus 10.0+6.5%; P=0.71) were all statistically similar between the prior preterm birth group and the healthy controls, respectively. CONCLUSION: There is an increased cytokine presence in vaginal washings of women at risk for preterm birth which appears to be modified following administration of 17- hydroxyprogesterone caproate compared with healthy controls.

T Cell Inhibition during Pregnancy Prevents Post‐partum Anxiety‐like Behavior in rats with a History of Severe Preeclampsia/HELLP Syndrome

INTRODUCTIONSevere preeclampsia and Hemolysis elevated liver enzyme low platelet (HELLP) syndrome, are potentially life threatening conditions with high maternal mortality and morbidity. During pregnancy these women have hypertension, increases in inflammatory cytokines, blood brain barrier (BBB) permeability and increased T cells. During the post‐partum period these women are reported to be at an increased risk of developing psychological disorders such as post‐traumatic stress disorder (PTSD). We have recently shown that T cell suppression to experimental HELLP rats during pregnancy attenuates inflammation, BBB permeability and hypertension. As T cells have been implicated in contributing to behavioral abnormalities, we hypothesized that T cell reduction during pregnancy to rats with HELLP could decrease the occurrence of anxiety‐like behavior in the post‐partum period.METHODSOn gestational day (GD) 12, mini‐osmotic pumps infusing sFlt‐1 and sEng were placed into rats to induce HELLP syndrome (n=28). A subset of HELLP rats (n=13) received 2 mg/kg of Orencia (Abatacept) on GD13 and all rats had their mini‐osmotic pumps removed 12–24 hrs post‐delivery to remove the source of sFlt‐1 and sEng. Rats without mini‐osmotic pumps served as normal pregnant (NP; n=14) controls. Beginning in the 4th post‐partum week rats underwent testing in marble burying, elevated plus maze (EPM) and locomotor activity. Mean arterial pressure was measured between postpartum day 46–48, tissue and plasma collection or Evan's blue (EB) infusion to assess BBB permeability.RESULTSPost‐partum HELLP rats buried significantly more marbles compared to NP (61.4 vs 38.9%; p=0.01) and HELLP+O rats (34.7%; p=0.05). HELLP rats also spent significantly more time in the closed arms of the EPM compared to NP (170.9 ± 14.1 vs 103.2 ± 16.6 sec; p=0.009) and HELLP+O rats (108.7± 20.4 sec; p=0.02). HELLP rats traveled a greater distance in the open field compared to NP (2571 ± 219.2 vs. 1777 ± 219.7 cm; p=0.02) and HELLP+O (1560 ± 166.6 cm; p=0.03). Rats with a history of HELLP syndrome had increased BBB permeability in the brainstem compared to NP rats (1.8 ± 0.5 vs 0.58 ± 0.1 (pg/g EB tissue)/μg/mL EB plasma; p=0.04), however this was reversed by treatment with Orencia (0.48 ± 0.13 (pg/g EB tissue)/μg/mL EB plasma; p=0.03). HELLP rats had significantly more circulating CD4+ T cells compared to NP rats (5.3 vs 2.18%; p=0.02). Similar results were seen in the liver where HELLP rats had significantly more hepatic CD4+ T cells compared to NP rats (2.9 vs 0.53%; p=0.03). HELLP rats had a significant increase in hepatic levels of IL‐6 (4.2 ± 0.44 vs 2.7 ± 0.49 pg/mg/mL; p=0.04) and IL‐1beta (31.9 ± 3.08 vs 21.9 ± 3.1pg/mg/mL; p=0.04) as well as increased sFlt‐1 (128.9 ± 13.4 vs 76.8 ± 13.9pg/mg/mL; p=0.02) compared to NP rats. There were no statistically significant changes between the groups in plasma levels of these proteins. Results on inflammation from rats treated with Orencia are pending. HELLP rats had significantly increased MAP compared to NP (136.8 ± 4.9 vs 115.3 ± 7.4 mmHg; p=0.02) and HELLP+O rats (117.2±4.7 mmHg; p=0.01).DISCUSSIONThese results suggest that HELLP syndrome during pregnancy contributes to an increase in anxiety‐like behavior, BBB permeability, liver inflammation, increased CD4+ T cells and hypertension in the post‐partum. The current results suggest that T cell suppression during pregnancy can also help prevent chronic hypertension and increased anxiety in the post‐partum period.Support or Funding InformationThis work was supported by the National Institutes of Health IDea grant P30GM103328 to KW.This abstract is from the Experimental Biology 2018 Meeting. There is no full text article associated with this abstract published in The FASEB Journal.

Regulation of pravastatin on long-chain fatty acid oxidative enzyme in pre-eclampsia-like mouse model

Objective: To investigate the modulation of long-chain 3-hydroxyacyl-CoA dehydrogenase (LCHAD) expression by pravastatin in pre-eclampsia-like mouse model. Methods: C57BL/6J mice were randomly injected with N-nitro-L-arginine methyl ester (L-NAME) as pre-eclampsia-like model group (PE) or saline as normal pregnancy control group (Con) respectively, from gestational the 7th to 18th day. For each group, pravastatin (PE+Pra, Con+Pra group) or saline (PE+N, Con+N Group) was given from the 8th to 18th day of gestation, respectively. Liver and placenta of pregnant mice were collected on gestational day 18. The LCHAD protein expression and mRNA levels of liver and placenta were detected through western blot, immunohistochemistry and real-time quantitative PCR. Results: (1) The average arterial pressure of pregnant mice increased gradually from the 8th to 18th day in PE+N group, but decreased in PE+Pra group from gestational 10th day, 24 hour urinary protein levels in PE+N group [(1 494 ± 201) μg] were significantly higher than that in Con+N group [(935±128) μg, P<0.01], and also higher than that in PE+Pra group [(981±116) μg, P<0.01].(2) The results of western blot: the expression of LCHAD was significantly lower in PE+N group (liver: 0.64±0.11, placenta: 0.48±0.06) than that in Con+N group (liver: 1.06±0.10, placenta: 0.60±0.10), and lower than that in PE+Pra group (liver: 0.99±0.04, placenta: 0.60±0.08; all P<0.01).(3)The results of real-time quantitative PCR: the levels of LCHAD mRNA in liver and placenta in PE+N group (liver: 0.621±0.128, placenta: 0.646±0.129) were significantly decreased compared with Con+N group (liver: 1.007±0.130, placenta: 1.004±0.103; all P<0.01), but there was no significant difference between PE+Pra group (liver: 0.693±0.678, placenta: 0.662±0.183; P>0.05). (4) LCHAD protein was expressed widely and evenly in liver. The expression in placental cytotrophoblast and syncytial trophoblast cells located in outer layer of villous in labyrinth layer was the most. The expression of LCHAD was significantly lower in PE+N group (liver: 0.062±0.016, placenta: 0.147±0.018) than that in Con+N group (liver: 0.126±0.013, placenta: 0.183±0.024), and lower than that in PE+Pra group (liver: 0.111±0.017, placenta: 0.174±0.027; all P<0.05). Conclusion: Pravastatin could upregulate the LCHAD protein expression of liver and placenta in the pre-eclampsia-like mouse, which may be a mechanism to improve the clinical manifestations of pre-eclampsia.

Cerebral Osmolytes and Plasma Osmolality in Pregnancy and Preeclampsia: A Proton Magnetic Resonance Spectroscopy Study.

Cerebral complications contribute substantially to mortality in preeclampsia. Pregnancy calls for extensive maternal adaptations, some associated with increased propensity for seizures, but the pathophysiology behind the eclamptic seizures is not fully understood. Plasma osmolality and sodium levels are lowered in pregnancy. This could result in extrusion of cerebral organic osmolytes, including the excitatory neurotransmitter glutamate, but this remains to be determined. The hypothesis of this study was that cerebral levels of organic osmolytes are decreased during pregnancy, and that this decrease is even more pronounced in women with preeclampsia. We used proton magnetic resonance spectroscopy to compare levels of cerebral organic osmolytes, in women with preeclampsia (n = 30), normal pregnancy (n = 32), and nonpregnant controls (n = 16). Cerebral levels of organic osmolytes were further correlated to plasma osmolality and plasma levels of glutamate and sodium. Compared to nonpregnant women, women with normal pregnancy and preeclampsia had lower levels of the cerebral osmolytes, myo-inositol, choline and creatine (P = 0.001 or less), and all these metabolites correlated with each other (P < 0.05). Women with normal pregnancies and preeclampsia had similar levels of osmolytes, except for glutamate, which was significantly lower in preeclampsia. Cerebral and plasma glutamate levels were negatively correlated with each other (P < 0.008), and myo-inositol, choline and creatine levels were all positively correlated with both plasma osmolality and sodium levels (P < 0.05). Our results indicate that pregnancy is associated with extrusion of cerebral organic osmolytes. This includes the excitatory neurotransmitter glutamate, which may be involved in the pathophysiology of seizures in preeclampsia.