Investigating human placentation and pregnancy using first trimester chorionic villi

Hannibal, Roberta L.; Cardoso-Moreira, Margarida; Chetty, Shilpa; Lau, Joanne; Qi, Zhongxia; Gonzalez-Maldonado, Eduardo; Cherry, Athena M.; Yu, Jingwei; Norton, Mary E.; Baker, Julie C.

doi:10.1016/j.placenta.2018.03.005

Cited by 9 publications

(6 citation statements)

References 22 publications

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“…The down-regulated ADM expression in CVS samples could be valuable for diagnosing EOPE in early pregnancy. CVS, a procedure used for fetal karyotype analysis, has excellent potential for predicting pregnancy complications and investigating human placentation ( 35 , 36 ). Compared with normotensive pregnancies, CVS samples of EOPE pregnancies exhibit differential gene expressions, such as VEGF ( VEGFA ), VEGFA receptor 1 ( Flt-1 ), and superoxide dismutase ( SOD ) ( 37 ).…”

Section: Discussionmentioning

confidence: 99%

Adrenomedullin has a pivotal role in trophoblast differentiation: A promising nanotechnology-based therapeutic target for early-onset preeclampsia

Zhang,

Lee,

Yang

et al. 2023

Sci. Adv.

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Early-onset preeclampsia (EOPE) is a severe pregnancy complication associated with defective trophoblast differentiation and functions at implantation, but manifestation of its phenotypes is in late pregnancy. There is no reliable method for early prediction and treatment of EOPE. Adrenomedullin (ADM) is an abundant placental peptide in early pregnancy. Integrated single-cell sequencing and spatial transcriptomics confirm a high ADM expression in the human villous cytotrophoblast and syncytiotrophoblast. The levels of ADM in chorionic villi and serum were lower in first-trimester pregnant women who later developed EOPE than those with normotensive pregnancy. ADM stimulates differentiation of trophoblast stem cells and trophoblast organoids in vitro. In pregnant mice, placenta-specific ADM suppression led to EOPE-like phenotypes. The EOPE-like phenotypes in a mouse PE model were reduced by a placenta-specific nanoparticle-based forced expression of ADM. Our study reveals the roles of trophoblastic ADM in placental development, EOPE pathogenesis, and its potential clinical uses.

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Section: Discussionmentioning

confidence: 99%

Adrenomedullin has a pivotal role in trophoblast differentiation: A promising nanotechnology-based therapeutic target for early-onset preeclampsia

Zhang,

Lee,

Yang

et al. 2023

Sci. Adv.

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“…To date, only one study showed that preeclampsia markers were associated with chorionic villi with low morphology scores and SVEP1 was positively correlated with increasing gestational age during early pregnancy. However, the relationship between preeclampsia and SVEP1 has not been determined [ 25 ]. LCAT converts cholesterol and phosphatidylcholines (lecithins) to cholesteryl esters and lysophosphatidylcholines on the surface of high-density lipoproteins (HDLs).…”

Section: Discussionmentioning

confidence: 99%

“…not been determined [25]. LCAT converts cholesterol and phosphatidylcholines (lecithins) to cholesteryl esters and lysophosphatidylcholines on the surface of high-density lipoproteins (HDLs).…”

Section: Plos Onementioning

confidence: 99%

Proteomic biomarkers in mid-trimester amniotic fluid associated with adverse pregnancy outcomes in patients with systemic lupus erythematosus

et al. 2020

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We aimed to explore the proteomic profiles of mid-trimester amniotic fluid in pregnant women with systemic lupus erythematosus (SLE) according to the occurrence of adverse pregnancy outcome (APO). The study population included 35 pregnant women with SLE who underwent clinically indicated amniocentesis at 15-24 weeks of gestation. Patients were divided into two groups according to pregnancy outcomes: SLE patients without APO (Group 1) and SLE patients with APO (Group 2). Stored samples of amniotic fluid were analyzed using mass spectrometry (MS)-based proteomics with two-step approach, consisting of discovery and verification phase. In the discovery phase, 44 proteins were differentially expressed between Group 1 and Group 2. In the verification phase, differentially expressed proteins (DEPs) were verified in independent samples using DIA method. Four proteins including filamin A (FLNA), sushi, von Willebrand factor type A, EGF and pentraxin domain containing 1 (SVEP1), lecithin-cholesterol acyltransferase (LCAT), and transglutaminase 2 (TGM2) were differentially expressed both in discovery and verification phase. To select the best combination of proteins for discriminating two groups, threefold cross validation (CV) with repetition of one hundred times was performed. The multi-marker model with three biomarkers (SVEP1, LCAT, TGM2) had a high discriminatory power to distinguish between the two groups (the area under the receiver operating characteristic, AUROC = 0.946, p <0.001). Our results indicate that the expression of FLNA, SVEP1, LCAT, and TGM2 in mid-trimester amniotic fluid was increased in SLE patients with APO (Group 2). A largescale prospective study is warranted to verify this finding.

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“…Placental chorionic villi serve as the functional and structural unit of the human placenta and are involved in the exchange of gas and nutrients between mother and fetus (Gude et al, 2004). During fetal development, chorionic villi grow and form branches as pregnancy progresses with high variability in vascularization, the degree of branching, and budding (Gude et al, 2004;Hannibal et al, 2018). Chorionic villus sampling (CVS) is conventionally conducted between weeks 10 and 14 during the first trimester (Jindal and Chaudhary, 2020).…”

Section: Background and Samplingmentioning

confidence: 99%

Drug exposure during pregnancy: Current understanding and approaches to measure maternal-fetal drug exposure

et al. 2023

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Prescription drug use is prevalent during pregnancy, yet there is limited knowledge about maternal-fetal safety and efficacy of this drug use because pregnant individuals have historically been excluded from clinical trials. Underrepresentation has resulted in a lack of data available to estimate or predict fetal drug exposure. Approaches to study fetal drug pharmacology are limited and must be evaluated for feasibility and accuracy. Anatomic and physiological changes throughout pregnancy fluctuate based on gestational age and can affect drug pharmacokinetics (PK) for both mother and fetus. Drug concentrations have been studied throughout different stages of gestation and at or following delivery in tissue and fluid biospecimens. Sampling amniotic fluid, umbilical cord blood, placental tissue, meconium, umbilical cord tissue, and neonatal hair present surrogate options to quantify and characterize fetal drug exposure. These sampling methods can be applied to all therapeutics including small molecule drugs, large molecule drugs, conjugated nanoparticles, and chemical exposures. Alternative approaches to determine PK have been explored, including physiologically based PK modeling, in vitro methods, and traditional animal models. These alternative approaches along with convenience sampling of tissue or fluid biospecimens can address challenges in studying maternal-fetal pharmacology. In this narrative review, we 1) present an overview of the current understanding of maternal-fetal drug exposure; 2) discuss biospecimen-guided sampling design and methods for measuring fetal drug concentrations throughout gestation; and 3) propose methods for advancing pharmacology research in the maternal-fetal population.

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Investigating human placentation and pregnancy using first trimester chorionic villi

Cited by 9 publications

References 22 publications

Adrenomedullin has a pivotal role in trophoblast differentiation: A promising nanotechnology-based therapeutic target for early-onset preeclampsia

Adrenomedullin has a pivotal role in trophoblast differentiation: A promising nanotechnology-based therapeutic target for early-onset preeclampsia

Proteomic biomarkers in mid-trimester amniotic fluid associated with adverse pregnancy outcomes in patients with systemic lupus erythematosus

Drug exposure during pregnancy: Current understanding and approaches to measure maternal-fetal drug exposure

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