Human Chorionic Villous Differentiation and Placental Development

Kojima, Junya; Ono, Masanori; Kuji, Naoaki; Nishi, Hirotaka

doi:10.3390/ijms23148003

Cited by 22 publications

(12 citation statements)

References 167 publications

(136 reference statements)

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“…This is an intriguing phenomenon. Previous studies have demonstrated that the presence of stromal cells surrounding placental villi plays a crucial role in stimulating angiogenesis in the placenta 31 . And the placental vascular development can significantly impact placental function, subsequently leading to fetal growth restriction.…”

Section: Discussionmentioning

confidence: 99%

“…Previous studies have demonstrated that the presence of stromal cells surrounding placental villi plays a crucial role in stimulating angiogenesis in the placenta. 31 And the placental vascular development can significantly impact placental function, subsequently leading to fetal growth restriction. In cases of severe fetal growth restriction, it has been observed that matrices derived from placental stromal cells impaired fetoplacental angiogenesis.…”

Section: Genesmentioning

confidence: 99%

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Placental DNA methylation analysis of selective fetal growth restriction in monochorionic twins reveals aberrant methylated CYP11A1 gene for fetal growth restriction

Shi,

Zhou,

Cai

et al. 2023

The FASEB Journal

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Fetal growth restriction (FGR) is associated with increased susceptibility to perinatal morbidity and mortality. Evidence suggests that epigenetic changes play critical roles in the regulation of fetal growth. We sought to present a comprehensive analysis of the associations between placental DNA methylation and selective fetal growth restriction (sFGR), which is a severe complication of monochorionic twin pregnancies, characterized by one fetus experiencing restricted growth. Genome‐wide methylation analysis was performed on 24 placental samples obtained from 12 monochorionic twins with sFGR (Cohort 1) using Illumina Infinium MethylationEPIC BeadChip. Integrative analysis of our EPIC data and two previous placental methylation studies of sFGR (a total of 30 placental samples from 15 sFGR twins) was used to identify convincing differential promoter methylation. Validation analysis was performed on the placentas from 15 sFGR twins (30 placental samples), 15 FGR singletons, and 14 control singletons (Cohort 2) using pyrosequencing, quantitative real‐time polymerase chain reaction, western blot, and immunohistochemistry (IHC). A globe shift toward hypomethylation was identified in the placentas of growth‐restricted fetuses compared with the placentas of normal fetuses in monochorionic twins, including 5625 hypomethylated CpGs and 452 hypermethylated CpGs, especially in the regions of CpG islands, gene‐body and promoters. The analysis of pathways revealed dysregulation primarily in steroid hormone biosynthesis, metabolism, cell adhesion, signaling transduction, and immune response. Integrative analysis revealed a differentially methylated promoter region in the CYP11A1 gene, encoding a rate‐limiting enzyme of steroidogenesis converting cholesterol to pregnenolone. The CYP11A1 gene was validated to have hypomethylation and higher mRNA expression in sFGR twins and FGR singletons. In conclusion, our findings suggested that the changes in placental DNA methylation pattern in sFGR may have functional implications for differentially methylated genes and regulatory regions. The study provides reliable evidence for identifying abnormally methylated CYP11A1 gene in the placenta of sFGR.

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Section: Discussionmentioning

confidence: 99%

Section: Genesmentioning

confidence: 99%

Placental DNA methylation analysis of selective fetal growth restriction in monochorionic twins reveals aberrant methylated CYP11A1 gene for fetal growth restriction

Shi,

Zhou,

Cai

et al. 2023

The FASEB Journal

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show abstract

“…Placental pathologies leading to FGR can occur at any step of the complex placental development. Often, the placenta shows reduced volume, surface and vascularization in fetuses with growth restriction, which can be due to the malregulation of certain molecular pathways [ 15 , 16 , 17 , 18 , 19 ].…”

Section: Introductionmentioning

confidence: 99%

Fetal Growth Restriction Is Associated with Pregnancy Associated Plasma Protein A and Uterine Artery Doppler in First Trimester

Springer

Worda

Franz

et al. 2023

JCM

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Fetal growth restriction (FGR) is a major cause of stillbirth and poor neurodevelopmental outcomes. The early prediction may be important to establish treatment options and improve neonatal outcomes. The aim of this study was to assess the association of parameters used in first-trimester screening, uterine artery Doppler pulsatility index and the development of FGR. In this retrospective cohort study, 1930 singleton pregnancies prenatally diagnosed with an estimated fetal weight under the third percentile were included. All women underwent first-trimester screening assessing maternal serum pregnancy-associated plasma protein A (PAPP-A), free beta-human chorionic gonadotrophin levels, fetal nuchal translucency and uterine artery Doppler pulsatility index (PI). We constructed a Receiver Operating Characteristics curve to calculate the sensitivity and specificity of early diagnosis of FGR. In pregnancies with FGR, PAPP-A was significantly lower, and uterine artery Doppler pulsatility index was significantly higher compared with the normal birth weight group (0.79 ± 0.38 vs. 1.15 ± 0.59, p < 0.001 and 1.82 ± 0.7 vs. 1.55 ± 0.47, p = 0.01). Multivariate logistic regression analyses demonstrated that PAPP-A levels and uterine artery Doppler pulsatility index were significantly associated with FGR (p = 0.009 and p = 0.01, respectively). To conclude, these two parameters can predict FGR < 3rd percentile.

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“…Extravillous trophoblasts (EVTs) are the dominant cell type involved in the process of placentation, invading deeply into the maternal decidua and uterine blood vessels, dissolving the extracellular matrix, remodeling the uterine vasculature, and coming into direct contact with the maternal decidua immune cells (DICs). The precise regulation of EVT invasion and remodeling of spiral arteries are key events of placentation [ 1 ]. As a result of placentation, the maternal immune system has to adapt to tolerate the semi-allogeneic fetus while maintaining maternal immune competence.…”

Section: Introductionmentioning

confidence: 99%

Tim-3 Coordinates Macrophage-Trophoblast Crosstalk via Angiogenic Growth Factors to Promote Pregnancy Maintenance

Cui

Sun

et al. 2023

IJMS

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T-cell immunoglobulin mucin-3 (Tim-3) is an important checkpoint that induces maternal–fetal tolerance in pregnancy. Macrophages (Mφs) play essential roles in maintaining maternal–fetal tolerance, remodeling spiral arteries, and regulating trophoblast biological behaviors. In the present study, the formation of the labyrinth zone showed striking defects in pregnant mice treated with Tim-3 neutralizing antibodies. The adoptive transfer of Tim-3+Mφs, rather than Tim-3-Mφs, reversed the murine placental dysplasia resulting from Mφ depletion. With the higher production of angiogenic growth factors (AGFs, including PDGF-AA, TGF-α, and VEGF), Tim-3+dMφs were more beneficial in promoting the invasion and tube formation ability of trophoblasts. The blockade of AGFs in Tim-3+Mφs led to the narrowing of the labyrinthine layer of the placenta, compromising maternal–fetal tolerance, and increasing the risk of fetal loss. Meanwhile, the AGFs-treated Tim-3-Mφs could resolve the placental dysplasia and fetal loss resulting from Mφ depletion. These findings emphasized the vital roles of Tim-3 in coordinating Mφs-extravillous trophoblasts interaction via AGFs to promote pregnancy maintenance and in extending the role of checkpoint signaling in placental development. The results obtained in our study also firmly demonstrated that careful consideration of reproductive safety should be taken when selecting immune checkpoint and AGF blockade therapies in real-world clinical care.

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Human Chorionic Villous Differentiation and Placental Development

Cited by 22 publications

References 167 publications

Placental DNA methylation analysis of selective fetal growth restriction in monochorionic twins reveals aberrant methylated CYP11A1 gene for fetal growth restriction

Placental DNA methylation analysis of selective fetal growth restriction in monochorionic twins reveals aberrant methylated CYP11A1 gene for fetal growth restriction

Fetal Growth Restriction Is Associated with Pregnancy Associated Plasma Protein A and Uterine Artery Doppler in First Trimester

Tim-3 Coordinates Macrophage-Trophoblast Crosstalk via Angiogenic Growth Factors to Promote Pregnancy Maintenance

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