The Critical Role of Abnormal Trophoblast Development in the Etiology of Preeclampsia

Huppertz, Berthold

doi:10.2174/1389201019666180427110547

Cited by 120 publications

(79 citation statements)

References 32 publications

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“…In the placenta, the cytotrophoblasts (CTs) stem cells undergo tightly regulated cellular processes of proliferation, cell death and differentiation in which cannabinoid signalling is involved (Battista et al 2015). Alterations in this complex trophoblast turnover can lead to pregnancy disorders like intrauterine growth restriction, preeclampsia, spontaneous abortion or miscarriage (Huppertz 2018). At the cellular and molecular level, several studies with THC in the µM range (up to 30 µM), which represents heavy cannabis consumption, have shown that THC directly interferes with CTs proliferation and gene transcription (Khare et al 2006), migration and invasion (Chang et al 2017), as well as angiogenesis in placentas of cannabis consumers (Chang et al 2018).…”

Section: Discussionmentioning

confidence: 99%

Effects of cannabis tetrahydrocannabinol on endocannabinoid homeostasis in human placenta

et al. 2019

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Cannabis use has become a hot topic in several countries due to the debate about its legalization for medical purposes. However, data are limited regarding adverse events, safety and potential impact on reproductive health. Cannabis consumption during pregnancy has been associated with gestational disorders such as preterm birth, intrauterine growth restriction, low birth weight and increased risk of miscarriage, though the underlying biochemical mechanisms are still unknown. Given that the endocannabinoid system (ECS) is involved in several reproductive processes, we tested the hypothesis that the negative outcomes may result from the impact on the ECS homeostasis caused by the main psychoactive compound of cannabis, Δ 9-tetrahydrocannabinol (THC). We demonstrate that THC (10-40 µM) impairs placental endocannabinoid system by disrupting the endocannabinoid anandamide (AEA) levels and the expression of AEA synthetic and degrading enzymes N-arachidonoylphosphatidylethanolamine-specific phospholipase D (NAPE-PLD) and fatty acid amide hydrolase (FAAH), respectively. Although, no alterations in cannabinoid receptors CB1 and CB2 expression were observed. Thus, long-term local AEA levels are associated with a shift in the enzymatic profile to re-establish ECS homeostasis. In chronic cannabis users, high AEA levels in placenta may disturb the delicate balance of trophoblast cells turnover leading to alterations in normal placental development and foetal growth.

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Section: Discussionmentioning

confidence: 99%

Effects of cannabis tetrahydrocannabinol on endocannabinoid homeostasis in human placenta

et al. 2019

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“…The more recent, modified two-stage model of PE explicitly elaborates on the difference between early-and late-onset PE based on the induction time of placental dysfunction and maternal susceptibility risk factors, such as chronic vascular disease [13]. The model describes several pathophysiologic mechanisms including oxidative stress, inflammation, senescence at the first stage, and general endothelial damage at the second stage [15][16][17]. However, the initial trigger of the disorder is still not known.…”

Section: Introductionmentioning

confidence: 99%

Maternal Exposure to Ambient Air Pollution and Risk of Preeclampsia: A Population-Based Cohort Study in Scania, Sweden

Mandakh

Rittner

Flanagan

et al. 2020

IJERPH

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The aim of this study was to investigate the risk of developing preeclampsia (PE) associated with gestational exposure to ambient air pollutants in southern Sweden, a low-exposure area. We used a cohort of 43,688 singleton pregnancies and monthly mean exposure levels of black carbon (BC), local and total particulate matter (PM 2.5 and PM 10 ), and NO X at the maternal residential address estimated by Gaussian dispersion modeling from 2000 to 2009. Analyses were conducted using binary logistic regression. A subtype analysis for small-for-gestational age (SGA) was performed. All analyses were adjusted for obstetrical risk factors and socioeconomic predictors. There were 1286 (2.9%) PE cases in the analysis. An adjusted odds ratio (AOR) of 1.35 with a 95% confidence interval (CI) of 1.11-1.63 was found when comparing the lowest quartile of BC exposure to the highest quartile in the third trimester The AOR for PE associated with each 5 µg/m 3 increase in locally emitted PM 2.5 was 2.74 (95% CI: 1.68, 4.47) in the entire pregnancy. Similar patterns were observed for each 5 µg/m 3 increment in locally emitted PM 10 . In pregnancies complicated by PE with SGA, the corresponding AOR for linear increases in BC was 3.48 (95% CI: 1.67, 7.27). In this low-level setting, maternal exposure to ambient air pollution during gestation was associated with the risk of developing PE. The associations seemed more pronounced in pregnancies with SGA complications, a finding that should be investigated further.

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“…The typical characteristics of PE include progressive hypertension, edema, proteinuria, and severe PE is characterized by degradation of maternal brain, degeneration of liver and kidney as well as dysfunction of placentas (Walker et al, ). The etiology of PE is still a mystery (Huppertz, ), but family history, infertility, oocyte donation, diabetes mellitus, and corpulence are suggested to contribute to PE (English, Kenny, & McCarthy, ). The diagnosis of PE mainly depends on clinical symptoms and physical signs, for instance, hypertension, vision disorders, bellyache, decreased fetal movement, and gestational age infants, and thus frequent laboratory tests and fetal health assessment are usually necessary (Alvarez‐Fernandez et al, ).…”

Section: Introductionmentioning

confidence: 99%

MicroRNA‐16 is involved in the pathogenesis of pre‐eclampsia via regulation of Notch2

Yuan

Wang

Sun

et al. 2019

Journal Cellular Physiology

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The Critical Role of Abnormal Trophoblast Development in the Etiology of Preeclampsia

Cited by 120 publications

References 32 publications

Effects of cannabis tetrahydrocannabinol on endocannabinoid homeostasis in human placenta

Effects of cannabis tetrahydrocannabinol on endocannabinoid homeostasis in human placenta

Maternal Exposure to Ambient Air Pollution and Risk of Preeclampsia: A Population-Based Cohort Study in Scania, Sweden

MicroRNA‐16 is involved in the pathogenesis of pre‐eclampsia via regulation of Notch2

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