Increased uterine NLRP3 inflammasome and leucocyte infiltration in a rat model of preeclampsia.

The disruption of the inflammatory microenvironment in the uterus affects pregnancy outcome. However, the exact quantification and distribution of leukocyte subpopulations in the uterus in preeclampsia (PE) have not been clearly characterized. Inflammasomes promote the release of proinflammatory cytokines interleukin (IL)-ß and IL-18. A higher expression of NLRP3 inflammasome in placentas contributes to excessive inflammation in PE. However, related studies on the uterus are scarce. We aimed to investigate changes in the infiltration of leukocyte subpopulations in decidual and uterine tissues, and explore the role of activation of uterine NLRP3 inflammasomes in PE. Decidual tissues were collected from normotensive pregnant women and preeclamptic women. A PE-like model was established via administration of lipopolysaccharide to normal pregnant rats. Uterine and decidual tissues were collected from all experimental groups. It was found that the number of leukocytes was significantly elevated in decidual and uterine tissues in PE patients compared to normal controls. The leukocytes (predominantly macrophages and NK cells) particularly infiltrated into the decidua and uterine decidua in PE-like rats, and these were sparse in the myometrium. The NLRP3 immunoreactivity in the uterus was extremely little in control rats, its immunoreactivity and caspase-1 immunoreactivity were significantly elevated in the PE-like rats; the mRNA expression results also indicated an upward trend in the activation of NLRP3 inflammasomes. These results support that leucocyte infiltration in the decidua and uterine deciduas, and the activation of NLRP3 inflammasome in the uterus, which participate in the pathogenesis, are responsible for the excessive inflammation at the maternal-fetal interface during PE.

Tissue Transglutaminase Impairs HTR-8/SVneo Trophoblast Cell Invasion via the PI3K/AKT Signaling Pathway.

OBJECTIVES: The pathogenesis of preeclampsia (PE) is associated with impaired trophoblast invasion, which results in placental insufficiency. Our earlier studies demonstrated that tissue transglutaminase (tTG) is highly expressed in human PE serum. However, whether tTG participates in trophoblast invasion remains unclear. The aim of the present study was to determine the role and mechanism of tTG in regulating matrix metalloproteinase (MMP)-2/MMP-9 expression to reduce trophoblast invasiveness in PE. METHODS: HTR-8/SVneo cells were transfected with a lentivirus vector and small interfering RNA targeting tTG. The protein level was detected by Western blotting. Cell proliferation and apoptosis were assessed by MTS and flow cytometry assays, respectively. Cell invasion was investigated by Transwell assay. In addition, the influence of tTG on PI3K and AKT mRNA levels in HTR-8/SVneo cells was evaluated using reverse transcription-quantitative PCR. RESULTS: tTG-overexpression inhibited HTR-8/SVneo cell proliferation and invasion and promoted apoptosis. In addition, upregulation of tTG induced an increase of PI3K and phosphorylated AKT and a decrease of MMP-2 and MMP-9 expression. tTG-knockdown significantly promoted the proliferation and invasion of HTR-8/SVneo cells and inhibited the apoptosis. Furthermore, the PI3K expression level was reduced, and the MMP-2/MMP-9 protein levels were increased. CONCLUSION: Taken together, the present study demonstrated that tTG-overexpression inhibited HTR-8/SVneo cell invasion via reducing the expression of MMP-2 and MMP-9 by activating PI3K/AKT signaling pathway, which may lead to the occurrence or development of PE. The present data provide new insights into modulation of tTG expression as a potential therapeutic target for PE.

The effects of epidural analgesia using low-concentration local anesthetic during the entire labor on maternal and neonatal outcomes: a prospective group study.

PURPOSE: The purpose of this study was to study the impact of epidural analgesia using low-concentration local anesthetic during the entire labor on maternal and neonatal outcomes. METHODS: The authors enrolled 2310 parturient mothers who underwent vaginal delivery at their hospital since January 1, 2019. The parturients were allocated either into the analgesia or into the non-analgesia groups based on whether they received analgesia during the delivery process. To investigate the effects of epidural analgesia using low-concentration local anesthetic on maternal and neonatal outcomes, the authors assessed between-group differences in the labor duration, newborn Apgar score, and maternal and neonatal outcomes. RESULTS: Compared to the non-analgesia group, the first and second labor stage durations in the analgesia group were significantly longer. Similarly, the analgesia group had a higher frequency of oxytocin injections, Category II and III fetal heart rate tracing during labor, and intrapartum fever development. Further, the need for episiotomy and assisted vaginal delivery was higher in the analgesia group than that in the non-analgesia group. Regarding neonatal outcomes, the neonatal hospitalization rate and incidence rate of umbilical cord blood pH < 7.2 were higher in the analgesia group than those in the non-analgesia group. However, there were no significant between-group differences in the incidence rates of stained amniotic fluid, mild neonatal asphyxia, and severe perinatal asphyxia. CONCLUSION: Patient-controlled epidural analgesia using low-concentration local anesthetic during the entire labor did not increase the incidence rate of severe adverse outcomes in neonates born through vaginal delivery; however, it increased the delivery duration, and thus, the chance of possible perinatal interventions.

Association between formaldehyde exposure and miscarriage in Chinese women.

The aim of this study was to assess whether higher plasma formaldehyde concentration existed in women diagnosed with miscarriage and whether it contributed to higher risk of miscarriage in Chinese women.A case-control study was conducted in 118 women with a diagnosed miscarriage at the first trimester and 191 healthy women who delivered at term. Plasma levels of formaldehyde were measured by gas chromatography in conjunction with mass spectrometry after derivatization of the formaldehyde to the pentafluorophenylhydrazone and characteristics of the subjects including age, education level, occupation, family income, home decoration status, and exposure to second-hand smoke were recorded. Logistic regression analyses were performed to investigate the relationship between miscarriage and levels of formaldehyde.Women with miscarriage were comparable to controls in terms of age, education level, occupation, family income, and home decoration status. They were, however, more likely to be exposed to second-hand smoke. Plasma levels of formaldehyde were significantly higher in women with miscarriage (0.0944 ±â€Š0.0105 vs. 0.0239 ±â€Š0.0032 µg/mL, P < .001). Multivariate logistic regression showed that higher level of formaldehyde (odds ratio [OR]: 8.06, 95% confidence interval [CI]: 4.96-13.09) and exposure to second-hand smoke (OR: 3.60, 95% CI: 1.58-8.20) were independently and significantly associated with higher risk of miscarriage.Plasma levels of formaldehyde were significantly higher in women who were diagnosed with miscarriage than those who delivered at term and higher levels of formaldehyde was an independent risk factor for miscarriage, with higher levels being associated with higher risk of miscarriage.