scholarly journals Elevated Circulating and Placental SPINT2 Is Associated with Placental Dysfunction

2021 ◽  
Vol 22 (14) ◽  
pp. 7467
Author(s):  
Ciara N. Murphy ◽  
Susan P. Walker ◽  
Teresa M. MacDonald ◽  
Emerson Keenan ◽  
Natalie J. Hannan ◽  
...  
Keyword(s):  
Stem Cells ◽  
First Trimester ◽  
Placental Insufficiency ◽  
Human Trophoblast ◽  
Trophoblast Stem Cells ◽  
Placental Dysfunction ◽  
Foetal Growth Restriction ◽  
Term Delivery ◽  
Placental Disease ◽  
Prospective Cohorts

Biomarkers for placental dysfunction are currently lacking. We recently identified SPINT1 as a novel biomarker; SPINT2 is a functionally related placental protease inhibitor. This study aimed to characterise SPINT2 expression in placental insufficiency. Circulating SPINT2 was assessed in three prospective cohorts, collected at the following: (1) term delivery (n = 227), (2) 36 weeks (n = 364), and (3) 24–34 weeks’ (n = 294) gestation. SPINT2 was also measured in the plasma and placentas of women with established placental disease at preterm (<34 weeks) delivery. Using first-trimester human trophoblast stem cells, SPINT2 expression was assessed in hypoxia/normoxia (1% vs. 8% O2), and following inflammatory cytokine treatment (TNFa, IL-6). Placental SPINT2 mRNA was measured in a rat model of late-gestational foetal growth restriction. At 36 weeks, circulating SPINT2 was elevated in patients who later developed preeclampsia (p = 0.028; median = 2233 pg/mL vs. controls, median = 1644 pg/mL), or delivered a small-for-gestational-age infant (p = 0.002; median = 2109 pg/mL vs. controls, median = 1614 pg/mL). SPINT2 was elevated in the placentas of patients who required delivery for preterm preeclampsia (p = 0.025). Though inflammatory cytokines had no effect, hypoxia increased SPINT2 in cytotrophoblast stem cells, and its expression was elevated in the placental labyrinth of growth-restricted rats. These findings suggest elevated SPINT2 is associated with placental insufficiency.

scholarly journals Isolation and characterisation of a novel trophoblast side-population from first trimester placentae

Reproduction ◽  
2015 ◽  
Vol 150 (5) ◽  
pp. 449-462 ◽  
Author(s):  
J L James ◽  
D G Hurley ◽  
T K J B Gamage ◽  
T Zhang ◽  
R Vather ◽  
...  
Keyword(s):  
Stem Cells ◽  
Stem Cell ◽  
Side Population ◽  
First Trimester ◽  
Placental Development ◽  
Human Trophoblast ◽  
Trophoblast Stem Cells ◽  
Trophoblast Stem ◽  
Future Work ◽  
Extravillous Trophoblasts

The placenta is responsible for all nutrient and gas exchange between mother and baby during pregnancy. The differentiation of specialised placental epithelial cells called trophoblasts is essential for placental function, but we understand little about how these populations arise. Mouse trophoblast stem cells have allowed us to understand many of the factors that regulate murine trophoblast lineage development, but the human placenta is anatomically very different from the mouse, and it is imperative to isolate a human trophoblast stem cell to understand human placental development. Here we have developed a novel methodology to isolate a Hoechst side-population of trophoblasts from early gestation placentae and compared their transcriptome to differentiated trophoblast populations (cytotrophoblasts and extravillous trophoblasts) using microarray technology. Side-population trophoblasts clustered as a transcriptomically distinct population but were more closely related to cytotrophoblasts than extravillous trophoblasts. Side-population trophoblasts up-regulated a number of genes characteristic of trophectoderm and murine trophoblast stem cells in comparison to cytotrophoblasts or extravillous trophoblasts and could be distinguished from both of these more mature populations by a unique set of 22 up-regulated genes, which were enriched for morphogenesis and organ development and the regulation of growth functions. Cells expressing two of these genes (LAMA2 and COL6A3) were distributed throughout the cytotrophoblast layer at the trophoblast/mesenchymal interface. Comparisons to previously published trophoblast progenitor populations suggest that the side-population trophoblasts isolated in this work are a novel human trophoblast population. Future work will determine whether these cells exhibit functional progenitor/stem cell attributes.

scholarly journals Generation of human induced trophoblast stem cells

2020 ◽  
Author(s):  
Gaël Castel ◽  
Dimitri Meistermann ◽  
Betty Bretin ◽  
Julie Firmin ◽  
Justine Blin ◽  
...  
Keyword(s):  
Stem Cells ◽  
Cell Fate ◽  
First Trimester ◽  
Alternative Methods ◽  
Extravillous Trophoblast ◽  
Human Embryos ◽  
List Type ◽  
Human Trophoblast ◽  
Trophoblast Stem Cells ◽  
Trophoblast Stem

SUMMARYHuman trophoblast stem cells (hTSC) derived from blastocysts and first-trimester cytotrophoblasts offer an unprecedented opportunity to study the human placenta. However, access to human embryos and first trimester placentas is limited thus preventing the establishment of hTSC from a variety of genetic backgrounds associated with placental disorders. In the present study, we show that hTSC can be generated from numerous genetic backgrounds using post-natal cells via two alternative methods: (I) somatic cell reprogramming of adult fibroblasts using the Yamanaka factors, and (II) cell fate conversion of naive and extended pluripotent stem cells. The resulted induced and converted hTSC (hiTSC/hcTSC) recapitulated hallmarks of hTSC including long-term self-renewal, expression of specific transcription factors, transcriptome-side signature, and the potential to differentiate into syncytiotrophoblast and extravillous trophoblast cells. We also clarified the developmental stage of hTSC and show that these cells resemble post-implantation NR2F2+ cytotrophoblasts (day 8-10). Altogether, hTSC lines of diverse genetics origins open the possibility to model both placental development and diseases in a dish.HighlightsReprogramming of human somatic cells to induced hTSC with OSKMConversion of naive and extended hPSC to hTSCGenetic diversity of hTSC linesDevelopmental matching of hTSC in the peri-implantation human embryo

scholarly journals Human trophoblast stem cells: Real or not real?

Placenta ◽  
2017 ◽  
Vol 60 ◽  
pp. S57-S60 ◽  
Author(s):  
Ching-Wen Chang ◽  
Mana M. Parast
Keyword(s):  
Stem Cells ◽  
Human Trophoblast ◽  
Trophoblast Stem Cells ◽  
Trophoblast Stem

scholarly journals Derivation of macaque trophoblast stem cells

2020 ◽  
Author(s):  
Jenna Kropp Schmidt ◽  
Michael G. Meyer ◽  
Gregory J. Wiepz ◽  
Lindsey N. Block ◽  
Brittany M. Dusek ◽  
...  
Keyword(s):  
Stem Cells ◽  
Culture Media ◽  
Syncytium Formation ◽  
First Trimester ◽  
Gonadotropin Secretion ◽  
Trophoblast Stem Cells ◽  
Trophoblast Stem ◽  
Mhc Class I Molecule

AbstractNonhuman primates are excellent models for studying human placentation as experimental manipulations in vitro can be translated to in vivo pregnancy. Our objective was to develop macaque trophoblast stem cells (TSC) as an in vitro platform for future assessment of primate trophoblast development and function. Macaque TSC lines were generated by isolating first trimester placental villous cytotrophoblasts followed by culture in TSC medium to “reprogram” the cells to a proliferative state. TSCs grew as mononuclear colonies, whereas upon induction of syncytiotrophoblast (ST) differentiation multinuclear structures appeared, indicative of syncytium formation. Chorionic gonadotropin secretion was >4,000-fold higher in ST culture media compared to TSC media. Characteristic trophoblast hallmarks were defined in TSCs and ST including expression of C19MC miRNAs and macaque placental nonclassical MHC class I molecule, Mamu-AG. TSC differentiation to extravillous trophoblasts (EVTs) with or without the ALK-5 inhibitor A83-01 resulted in differing morphologies but similar expression of Mamu-AG and CD56 as assessed by flow cytometry, hence further refinement of relevant EVT markers is needed. Our preliminary characterization of macaque TSCs suggests that these cells represent a proliferative, self-renewing TSC population capable of differentiating to STs in vitro thereby establishing an experimental model of primate placentation.

scholarly journals Telomeric NAP1L4 and OSBPL5 of the KCNQ1 Cluster, and the DECORIN Gene Are Not Imprinted in Human Trophoblast Stem Cells

PLoS ONE ◽  
2010 ◽  
Vol 5 (7) ◽  
pp. e11595 ◽  
Author(s):  
Jennifer M. Frost ◽  
Ramya Udayashankar ◽  
Harry D. Moore ◽  
Gudrun E. Moore
Keyword(s):  
Stem Cells ◽  
Human Trophoblast ◽  
Trophoblast Stem Cells ◽  
Trophoblast Stem

scholarly journals Human placenta-derived stem cells - recent findings based on the molecular science

2020 ◽  
Vol 8 (4) ◽  
pp. 164-169
Author(s):  
Rafał Sibiak ◽  
Michał Jaworski ◽  
Zuzanna Dorna ◽  
Wojciech Pieńkowski ◽  
Katarzyna Stefańska ◽  
...  
Keyword(s):  
Stem Cells ◽  
Human Placenta ◽  
Current Knowledge ◽  
Placental Tissue ◽  
First Trimester ◽  
Blastocyst Stage ◽  
Trophoblast Stem Cells ◽  
Decidua Basalis ◽  
Degenerative Disorders

AbstractThe human placenta is a complex, multifunctional transient fetomaternal organ. The placenta is composed of the maternal decidua basalis and its fetal part, consisting of the mesenchymal and trophoblast cell lineages. Both the placenta and the amniotic membranes are abundant in readily available placenta-derived mesenchymal stem cells (PD-MSCs). The clinical application of the PD-MSCs opens new perspectives for regenerative medicine and the treatment of various degenerative disorders. Their properties depend on their paracrine activity – the secretion of the anti-inflammatory cytokines and specific exosomes. In contrast to the PD-MSCs, the trophoblast stem cells (TSCs) are much more elusive. They can only be isolated from the blastocyst-stage embryos or the first-trimester placental tissue, making that procedure quite demanding. Also, other cultures require specific, strictly controlled conditions. TSCs may be potentially used as an in vitro model of various placental pathologies, facilitating the elucidation of their mysterious pathogenesis and creating the environment for testing the new drug efficiency. Nonetheless, it is unlikely that they could be ever implemented as a part of novel cellular therapeutic strategies in humans.Running title: Current knowledge on the placental stem cells

scholarly journals Efficient derivation of human trophoblast stem cells from primed pluripotent stem cells

2021 ◽  
Vol 7 (33) ◽  
pp. eabf4416
Author(s):  
Yanxing Wei ◽  
Tianyu Wang ◽  
Lishi Ma ◽  
Yanqi Zhang ◽  
Yuan Zhao ◽  
...  
Keyword(s):  
Stem Cells ◽  
Pluripotent Stem Cells ◽  
Chromatin Accessibility ◽  
Placental Development ◽  
Differentiation Potential ◽  
Human Trophoblast ◽  
Trophoblast Stem Cells ◽  
Trophoblast Stem ◽  
Early Placenta ◽  
And Function

Human trophoblast stem cells (hTSCs) provide a valuable model to study placental development and function. While primary hTSCs have been derived from embryos/early placenta, and transdifferentiated hTSCs from naïve human pluripotent stem cells (hPSCs), the generation of hTSCs from primed PSCs is problematic. We report the successful generation of TSCs from primed hPSCs and show that BMP4 substantially enhances this process. TSCs derived from primed hPSCs are similar to blastocyst-derived hTSCs in terms of morphology, proliferation, differentiation potential, and gene expression. We define the chromatin accessibility dynamics and histone modifications (H3K4me3/H3K27me3) that specify hPSC-derived TSCs. Consistent with low density of H3K27me3 in primed hPSC-derived hTSCs, we show that knockout of H3K27 methyltransferases (EZH1/2) increases the efficiency of hTSC derivation from primed hPSCs. Efficient derivation of hTSCs from primed hPSCs provides a simple and powerful model to understand human trophoblast development, including the pathogenesis of trophoblast-related disorders, by generating disease-specific hTSCs.

Pregnancy after influenza in the first trimester

2018 ◽  
pp. 14-18
Author(s):  
V.V. Kaminskyi ◽  
◽  
O.I. Zhdanovich ◽  
T.V. Kolomiychenko ◽  
A.D. Derkach ◽  
...  
Keyword(s):  
Pregnant Women ◽  
High Frequency ◽  
Clinical Manifestations ◽  
Birth Asphyxia ◽  
Fetal Distress ◽  
First Trimester ◽  
Placental Insufficiency ◽  
Perinatal Complications ◽  
Placental Dysfunction ◽  
First Trimester Of Pregnancy

The endpoint of the negative impact of adverse processes in the mother’s body with influenza is the formation of placental insufficiency, the basis of which is a violation of the uteroplacental blood flow. The objective: to study the features of the course of pregnancy, the state of the fetus and the newborn after the influenza in the first trimester of pregnancy. Materials and methods. 120 women who had the influenza in the first trimester of pregnancy were examined. In 68 (56.7%) pregnant women signs of feto-placental dysfunction were observed, 2 groups were distinguished: the main group - 68 patients with feto-placental dysfunction, the comparison group – 52 pregnant women without signs of feto-placental insufficiency. Results. 3 times more often than women without manifestations of placental insufficiency (42.6% versus 15.4%; p<0.05) a severe course of influenza was observed, it accompanied by a high frequency of clinical manifestations, including in almost all patients (95.6% versus 67.3%; p<0.05), body temperature rose to 38 °C and higher, and in 61.7% of women it stayed for 4–6 days (versus 11.5%; p<0.05). Among the complications of influenza: bronchitis (25.0% versus 9.3%; p<0.05), pneumonia (17.6% versus 5.7%; p<0.05), sinusitis (17.6% versus 7.7%; p<0.05). The threat of abortion was noted in 57.4% of cases, the threat of preterm birth was observed in 39.7% of women. Most often, placental dysfunction was associated with fetal distress (76.5% versus 13.5%; p<0.05) and growth retardation (54.4% versus 3.8%; p<0.05). 32.4% versus 13.5% of women had preeclampsia (p<0.05). The frequency of both polyhydramnios (17.6%) and low water (10.3%) is significantly higher. By cesarean section, 35.3% women were delivered (versus 15.4%, (p<0.05). Delivery was preterm in 17.6% of women versus 7.7% (p<0.05). Premature discharge of amniotic fluid (17.6%) and pathological blood loss during childbirth (16.2%), fetal distress during childbirth (48.5% versus 9.6%; p<0.05) were noted. Maternal placental dysfunction, fetal distress, prematurity (17.6%) and malnutrition (22.1%) led to a high incidence of birth asphyxia (46.5% versus 19.2%, p <0.05). Half (51.5%) of children had disadaptation syndromes, most often neurological disorders (32.4% versus 11.5%; p<0.05) and respiratory disorders (27.9% versus 7.7%; p<0.05). Conclusion. Influenza in early pregnancy with a severe course and a high frequency of complications is associated with a high frequency of feto-placental dysfunction and other obstetric and perinatal complications, which requires a more detailed study to determine risk factors and develop tactics for managing this category of pregnant women. Keywords: pregnancy, influenza, feto-placental dysfunction, obstetric and perinatal complications, newborn.

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