Decreased Maternal Serum 2-Methoxyestradiol Levels are Associated with the Development of Preeclampsia

Background/Aims: The placenta is a vital organ for pregnancy. Many in vitro placental experiments are conducted under 21% O₂; however, O₂ tension could influence cellular functions, including cytokine secretion. We investigated the effects of oxygen tension between moderate hypoxia (5% O₂) and normoxia (21% O₂) by testing the hypothesis that moderate hypoxia regulates cellular phenotypes differently from normoxia in human trophoblast cells. Methods and Results: Sw.71 trophoblast cells were incubated under normoxic or moderately hypoxic conditions. Cells were also treated with lipopolysaccharide (LPS) as a Toll-like receptor 4 (TLR4) ligand inducing inflammation. Interleukin-6 (IL-6) as an inflammatory cytokine was determined, and TLR4, hypoxia-induced factor-1α (HIF1α), and reactive oxygen species (ROS) production were detected. Moderate hypoxia increased HIF1α expression and cell proliferation and acted by two different mechanisms to decrease IL-6 secretion compared with normoxia: it limits the TLR4 expression and ROS production. Treatment with cobalt chloride as an HIF1 activator inhibited IL-6 secretion and TLR4 expression; this effect was reversed on treatment with PX-12 as an HIF1 suppressor. Conclusion: IL-6 secretion, TLR4 expression, and ROS production, classical markers of inflammation, are down-regulated by moderate hypoxia, and HIF1α and ROS have a potential to regulate these responses in human trophoblast cells.

Section: Discussionmentioning

confidence: 99%

Moderate Hypoxia Down-Regulates Interleukin-6 Secretion and TLR4 Expression in Human Sw.71 Placental Cells

Shirasuna

Shimamura

Seno

et al. 2015

“…As more states have passed laws legalizing marijuana for recreational and medical use in United States, the rate of marijuana usage during pregnancy will likely grow. Although the placenta acts as a barrier to protect the fetus from toxic chemicals present in the maternal bloodstream [10], THC readily crosses the placenta and enters into the fetal bloodstream [11]. Consequently, THC may act to alter the normal function of placental trophoblasts, fetal development and influence the growth of newborns as it is also detected in breast milk [12].…”

Section: Introductionmentioning

confidence: 99%

Suppression of STAT3 Signaling by Δ9-Tetrahydrocannabinol (THC) Induces Trophoblast Dysfunction

Chang¹,

Bian²,

He³

et al. 2017

Self Cite

Aims: Marijuana is a widely used illicit drug and its consumption during pregnancy has been associated with adverse reproductive outcomes. The purpose of this study was to determine the effects of chronic intake of Δ⁹-tetrahydrocannabinol (THC), the major component of marijuana, on trophoblast function, placental development, and birth outcomes. Methods: The pathological characteristics and distribution of cannabinoid receptors in placenta were observed by immunohistochemical (IHC) staining. Cell migration in response to THC was measured by transwell assays. The levels of cannabinoid receptors and Signal Transducer and Activator of Transcription 3 (STAT3) were detected by western blot. Results: We found the placenta expressed two main cannabinoid receptors, suggesting that THC induced biological responses in placental cells. Supporting this hypothesis, we observed dramatic alterations of placental morphology in marijuana users. Using THC and inhibitors of cannabinoid receptors, we demonstrated that THC impaired trophoblast cell migration and invasion partly via cannabinoid receptors. Additionally, pregnant mice injected with THC showed adverse reproductive events including reduced number of fetuses, lower maternal and placental weights. Mechanistically, STAT3 signaling pathway was involved in the THC-induced suppression of trophoblast cell motility and pregnancy outcomes. Conclusion: Our study indicates that the STAT3 signaling pathway plays a critical role in THC-induced trophoblast dysfunction.

“…Several epidemiological studies that investigated the incidence of preeclampsia by ethnicity/race observed the prevalence of preeclampsia is approximately 50% lower in the Asian population when compared with Caucasians [2][3][4][5]. Although genetic differences might play an important role [6,7], whether a high rate of chronic hepatitis B virus (CHB) infection in the Asian population may influence the incidence of preeclampsia [8,9], have not been examined before.…”

Section: Introductionmentioning

confidence: 99%

Chronic Hepatitis B Infection is Associated with Decreased Risk of Preeclampsia: A Meta-Analysis of Observational Studies

Huang

Chen

Zhong

et al. 2016

Background/Aims: Preeclampsia is a complex multi-system obstetric syndrome and remains one of the leading causes contributing to maternal and perinatal mortality and morbidity. Previous epidemiological studies regarding the association between chronic hepatitis B virus (CHB) infection and the risk of preeclampsia have reported inconsistent results. Therefore, we conducted a meta-analysis to investigate the association between CHB infection and preeclampsia. Methods: The electronic database was searched until January 1st, 2016. Relevant studies reporting the association between CHB infection and the risk of preeclampsia were included and for further evaluation. Statistical analysis was performed using Stata 10.0 (Stata Corp). Results: Three observational cohort studies and eight case-control studies, including 11566 preeclampsia patients, were identified. A significant negative association between CHB infection and preeclampsia was observed (odds ratio = 0.77, 95% confidence interval, 0.65- 0.90, P=0.002, fixed-effect model). Conclusions: Findings from our meta-analysis indicate that CHB infection may decrease the risk of preeclampsia in Asian population. Future prospective cohorts in different countries with larger sample sizes are warranted to ascertain the causality and pathophysiological studies are required to explore the possible biological mechanisms involved.