scholarly journals Megalin Is Predominantly Observed in Vesicular Structures in First and Third Trimester Cytotrophoblasts of the Human Placenta

2016 ◽  
Vol 64 (12) ◽  
pp. 769-784 ◽  
Author(s):  
Tina Storm ◽  
Erik I. Christensen ◽  
Julie Nelly Christensen ◽  
Tine Kjaergaard ◽  
Niels Uldbjerg ◽  
...  
Keyword(s):  
Human Placenta ◽  
Fetal Development ◽  
First Trimester ◽  
Main Role ◽  
Third Trimester ◽  
Term Placenta ◽  
Complex Functions ◽  
And Function ◽  
Uptake Of Nutrients ◽  
Immunohistochemical Analyses

The membrane receptor megalin is crucial for normal fetal development. Besides its expression in the developing fetus, megalin is also expressed in the human placenta. Similar to its established function in the kidney proximal tubules, placental megalin has been proposed to mediate uptake of vital nutrients. However, details of megalin expression, subcellular localization, and function in the human placenta remain to be established. By immunohistochemical analyses of first trimester and term human placenta, we showed that megalin is predominantly expressed in cytotrophoblasts, the highly proliferative cells in placenta. Only limited amounts of megalin could be detected in syncytiotrophoblasts and least in term placenta syncytiotrophoblasts. Immunocytochemical analyses furthermore showed that placental megalin associates with structures of the endolysosomal apparatus. Combined, our results clearly place placental megalin in the context of endocytosis and trafficking of ligands. However, due to the limited expression of megalin in syncytiotrophoblasts, especially in term placenta, it appears that the main role for placental megalin is not to mediate uptake of nutrients from the maternal bloodstream, as previously proposed. In contrast, our results point toward novel and complex functions for megalin in the cytotrophoblasts. Thus, we propose that the perception of placental megalin localization and function should be revised.

scholarly journals Monocarboxylate transporter 8 expression in the human placenta: the effects of severe intrauterine growth restriction

2006 ◽  
Vol 189 (3) ◽  
pp. 465-471 ◽  
Author(s):  
S-Y Chan ◽  
J A Franklyn ◽  
H N Pemberton ◽  
J N Bulmer ◽  
T J Visser ◽  
...  
Keyword(s):  
Human Placenta ◽  
Fetal Development ◽  
Intrauterine Growth Restriction ◽  
First Trimester ◽  
Growth Restriction ◽  
Monocarboxylate Transporter ◽  
Trophoblast Cells ◽  
Third Trimester ◽  
Neurodevelopmental Delay ◽  
Intrauterine Growth

Thyroid hormones (THs) are essential for normal fetal development, with even mild perturbation in maternal thyroid status in early pregnancy being associated with neurodevelopmental delay in children. Transplacental transfer of maternal THs is critical, with increasing evidence suggesting a role for 3,3′,5-tri-iodothyronine (T3) in development and function of the placenta itself, as well as in development of the central nervous and other organ systems. Intrauterine growth restriction (IUGR) is associated with fetal hypothyroxinaemia, a factor that may contribute to neurodevelopmental delay. The recent description of monocarboxylate transporter 8 (MCT8) as a powerful and specific TH membrane transporter, and the association of MCT8 mutations with profound neurodevelopmental delay, led us to explore MCT8 expression in placenta. We describe the expression of MCT8 in normal human placenta throughout gestation, and in normal third-trimester placenta compared with that associated with IUGR using quantitative reverse transcriptase PCR. MCT8 mRNA was detected in placenta from early first trimester, with a significant increase with advancing gestation (P=0.007). In the early third trimester, MCT8 mRNA was increased in IUGR placenta compared with normal samples matched for gestational age (P<0.05), but there was no difference between IUGR and normal placenta in the late third trimester. Western immunoblotting findings in IUGR and normal placentae were in accord with mRNA data. MCT8 immunostaining was demonstrated in villous cytotrophoblast and syncytiotrophoblast as well as extravillous trophoblast cells from the first trimester onwards with increasingly widespread immunoreactivity seen with advancing gestation. In conclusion, expression of MCT8 in placenta from early gestation is compatible with an important role in TH transport during fetal development and a specific role in placental development. Altered expression in placenta associated with IUGR may reflect a compensatory mechanism attempting to increase T3 uptake by trophoblast cells.

scholarly journals Modulation of Wolframin Expression in Human Placenta during Pregnancy: Comparison among Physiological and Pathological States

2014 ◽  
Vol 2014 ◽  
pp. 1-7 ◽  
Author(s):  
Angela Lucariello ◽  
Angelica Perna ◽  
Carmine Sellitto ◽  
Alfonso Baldi ◽  
Alessandro Iannaccone ◽  
...  
Keyword(s):  
Human Placenta ◽  
Autosomal Recessive Disorder ◽  
Cell Loss ◽  
Wolfram Syndrome ◽  
First Trimester ◽  
Third Trimester ◽  
Gene Encoding ◽  
Cytotrophoblast Cell ◽  
The Third ◽  
Normal Placenta

TheWFS1gene, encoding a transmembrane glycoprotein of the endoplasmic reticulum called wolframin, is mutated in Wolfram syndrome, an autosomal recessive disorder defined by the association of diabetes mellitus, optic atrophy, and further organ abnormalities. Disruption of theWFS1gene in mice causes progressiveβ-cell loss in the pancreas and impaired stimulus-secretion coupling in insulin secretion. However, little is known about the physiological functions of this protein. We investigated the immunohistochemical expression of wolframin in human placenta throughout pregnancy in normal women and diabetic pregnant women. In normal placenta, there was a modulation of wolframin throughout pregnancy with a strong level of expression during the first trimester and a moderate level in the third trimester of gestation. In diabetic women, wolframin expression was strongly reduced in the third trimester of gestation. The pattern of expression of wolframin in normal placenta suggests that this protein may be required to sustain normal rates of cytotrophoblast cell proliferation during the first trimester of gestation. The decrease in wolframin expression in diabetic placenta suggests that this protein may participate in maintaining the physiologic glucose homeostasis in this organ.

The human placenta expresses transcription enhancer factor-1 but there is no correlation with the expression of placental lactogen

1996 ◽  
Vol 16 (2) ◽  
pp. 205-210 ◽  
Author(s):  
G Quinn ◽  
D S W Boam ◽  
J R E Davis ◽  
J D Glazier ◽  
P Mylona ◽  
...  
Keyword(s):  
Human Placenta ◽  
First Trimester ◽  
Placental Lactogen ◽  
Transcriptional Enhancer ◽  
Term Placenta ◽  
Consensus Binding Sequence ◽  
Cytotrophoblast Cells ◽  
Binding Sequence ◽  
Transcription Enhancer ◽  
Enhancer Factor

ABSTRACT A transcriptional enhancer which has a consensus binding sequence for transcription enhancer factor-1 (TEF-1) has been found 3′ of the hPL3 gene. We examined whether TEF-1 is expressed by the human placenta and whether such expression is co-ordinated with that of human placental lactogen (hPL). Probing Northern blots of total RNA from first trimester and term placenta, the choriocarcinoma-derived cell line JAr and primary cultured cytotrophoblast cells with a cDNA for TEF-1 revealed transcripts of 12–13 kb and 3–4 kb. The level of TEF-1 expression was the same in first trimester as compared with term placenta and in undifferentiated JAr as compared with differentiated cytotrophoblast cells. hPL expression was tenfold higher in term compared with first trimester placenta and, whilst detectable in cytotrophoblast cells, was undetectable in JAr cells. These data show that TEF-1 is expressed by the placenta but is not co-ordinated with hPL expression.

scholarly journals High-throughput miRNA sequencing of the human placenta: expression throughout gestation

Epigenomics ◽  
2021 ◽  
Author(s):  
Tania L Gonzalez ◽  
Laura E Eisman ◽  
Nikhil V Joshi ◽  
Amy E Flowers ◽  
Di Wu ◽  
...  
Keyword(s):  
Human Placenta ◽  
First Trimester ◽  
Fold Change ◽  
Prognostic Indicators ◽  
Mirna Cluster ◽  
Third Trimester ◽  
Healthy Human ◽  
Functional Studies ◽  
Mirna Clusters ◽  
Mirna Sequencing

Aim: To understand miRNA changes across gestation in healthy human placentae. This is essential before miRNAs can be used as biomarkers or prognostic indicators during pregnancy. Materials & methods: Using next-generation sequencing, we characterize the normative human placenta miRNome in first (n = 113) and third trimester (n = 47). Results & conclusion: There are 801 miRNAs expressed in both first and third trimester, including 182 with similar expression across gestation (p ≥ 0.05, fold change ≤2) and 180 significantly different (false discovery rate <0.05, fold change >2). Of placenta-specific miRNA clusters, chromosome 14 miRNA cluster decreases across gestation and chromosome 19 miRNA cluster is overall highly expressed. Chromosome 13 clusters are upregulated in first trimester. This work provides a rich atlas of healthy pregnancies to direct functional studies investigating the epigenetic differences in first and third trimester placentae.

scholarly journals High-throughput miRNA-sequencing of the human placenta: expression throughout gestation

2021 ◽  
Author(s):  
Tania L Gonzalez ◽  
Laura E Eisman ◽  
Nikhil V Joshi ◽  
Amy E Flowers ◽  
Di Wu ◽  
...  
Keyword(s):  
Next Generation Sequencing ◽  
Human Placenta ◽  
First Trimester ◽  
Prognostic Indicators ◽  
Next Generation ◽  
Third Trimester ◽  
Functional Studies ◽  
Microrna Profile ◽  
Mirna Clusters ◽  
Generation Sequencing

AbstractBackgroundAltered placenta miRNA abundance may impact the maternal-fetal interface and pregnancy outcomes. Understanding miRNA changes across gestation is essential before miRNAs can be used as biomarkers or prognostic indicators during pregnancy.Materials & MethodsUsing next-generation sequencing, we characterize the normative human placenta miRNA transcriptome in first (N=113) and third trimester (N=47).ResultsThere are 801 miRNAs expressed in both first and third trimester, including 182 with similar expression across gestation (P≥0.05) and 182 significantly different (FDR<0.05). Of placenta-specific miRNA clusters, C14MC is more upregulated in first trimester and C19MC is more highly expressed overall.ConclusionThis work provides a rich atlas of healthy pregnancies to direct functional studies investigating the epigenetic differences in first and third trimester placentae.Lay AbstractThe human body produces microRNAs which affect the expression of genes and proteins. This study uses next generation sequencing to identify the microRNA profile of first and third trimester human placentae using a large cohort (N=113 first, N=47 third trimester). All pregnancies resulted in healthy babies. We identify microRNAs with significantly different expression between first and third trimester, as well as stably expressed microRNAs. This work provides a baseline for future studies which may use microRNAs to monitor maternal-fetal health throughout pregnancy.

207. The expression of caspase-14 in the human placenta

2005 ◽  
Vol 17 (9) ◽  
pp. 79
Author(s):  
A. Charles ◽  
S. Hisheh ◽  
D. W. R. Kam ◽  
A. M. Dharmarajan
Keyword(s):  
Human Placenta ◽  
First Trimester ◽  
Explant Culture ◽  
Control Group ◽  
Term Placenta ◽  
Protein Levels ◽  
Significant Difference ◽  
Cytotrophoblast Cells ◽  
Immunohistochemical Studies

Pro-apoptotic genes have a role in the differentiation process in the placenta leading to the fusion of cytotrophoblast cells to form the protective syncytiotrophoblast layer. The mechanisms of apoptosis in the human placenta are not clearly understood. However, a major placental apoptotic-signalling pathway is known to involve the caspases. Caspase-14 is the most recently discovered member of the caspase family members and has not previously been examined in the human placenta. The aim of the present study was to detect caspase-14 in the human placenta and study its role in apoptosis. Human placentae were collected from first trimester and term gestation. The study consisted of two parts. In the first part, first trimester and term placentae were assessed for caspase-14 by western blotting and mRNA analysis and localised with immunohistochemical studies. In the second part, apoptosis in first trimester placenta was inhibited in an in-vitro model of explant villi culture with superoxide dismutase (SOD) treatment and the genes assessed. The first study demonstrated caspase-14 to be a cytoplasmic protein localised in the cytotrophoblast cells, the mesenchyme and in the syncytiotrophoblast of the first trimester. In the term placenta, caspase-14 was expressed weakly in the syncytiotrophoblast. The immunostaining data suggest a higher expression of caspase-14 in the first trimester compared to the term placenta, and this observation was later confirmed by western blot analysis. Using the SOD in-vitro explant culture model, no significant difference in the caspase-14 protein levels were seen in either the SOD or control group. This novel study demonstrates for the first time that caspase-14 protein and mRNA are present in the human placenta. The function of caspase-14 in the human placenta is unclear.

Characterization and ontogeny of endothelin receptors in human placenta

1993 ◽  
Vol 264 (3) ◽  
pp. E367-E372 ◽  
Author(s):  
S. J. Kilpatrick ◽  
J. M. Roberts ◽  
D. L. Lykins ◽  
R. N. Taylor
Keyword(s):  
Human Placenta ◽  
Binding Sites ◽  
Pregnancy Termination ◽  
First Trimester ◽  
Receptor Subtype ◽  
Rt Pcr ◽  
Third Trimester ◽  
Single Class ◽  
Mrna Transcripts ◽  
Polymerase Chain

Because of the potent mitogenic and vasoactive properties of endothelin-1 (ET-1) and the presence of its receptor in third trimester placenta, we postulated that ET-1 might be involved in human placental growth and vascularization during development. As an initial approach to test this hypothesis, placental ET receptors were characterized and quantified in each trimester of pregnancy. Membrane-rich particulates were prepared from first-, second-, and third-trimester villous human placenta obtained immediately after pregnancy termination or delivery. ET receptors were characterized by radioligand saturation analysis, ligand competition, and reverse transcription-polymerase chain reaction (RT-PCR) to determine the concentration, affinity, and specificity of ET binding sites, and to document the presence of specific ET-receptor subtype mRNA transcripts in placentas from each trimester. Kinetic determinations of 125I-labeled ET-1 binding yielded a Kd = 61 pM, consistent with the equilibrium determinations of 34 +/- 6 pM (n = 11). The concentration of ET receptors decreased significantly from 682 +/- 94 fmol/mg protein (n = 4) in the first trimester to 266 +/- 89 fmol/mg protein (n = 4) in the third trimester. Competition studies with unlabeled ET-1 indicated a single class of binding sites with a Ki = 49 +/- 5 pM (n = 9), whereas competition with ET-3 demonstrated binding sites with two affinities. The predominant sites had a Ki = 84 +/- 14 pM, similar to that for ET-1. The RT-PCR data confirmed that both ETA and ETB receptors mRNA transcripts are expressed in human placenta.(ABSTRACT TRUNCATED AT 250 WORDS)

scholarly journals Sex Differences in the Human Placenta MicroRNA Transcriptome

2021 ◽  
Vol 5 (Supplement_1) ◽  
pp. A753-A753
Author(s):  
Amy E Flowers ◽  
Tania L Gonzalez ◽  
Laura E Eisman ◽  
Nikhil Joshi ◽  
Di Wu ◽  
...  
Keyword(s):  
Sex Differences ◽  
Human Placenta ◽  
Mirna Expression ◽  
Expression Profiles ◽  
Differential Expression Analysis ◽  
First Trimester ◽  
Sexually Dimorphic ◽  
Third Trimester ◽  
Fetal Sex ◽  
Mirna Expression Profiles

Abstract Maternal and fetal pregnancy outcomes vary based on fetal sex likely due to differences in placental function, reflected by sex differences in RNA expression. RNA transcripts are subject to fine-tuning control by post-transcriptional regulation including miRNAs binding to target RNAs and altering gene expression. Here we identify sexually dimorphic miRNA expression throughout gestation in the human placenta. Next-generation sequencing was used to identify human placenta miRNA expression profiles in first and third trimester uncomplicated pregnancies using discarded tissue obtained after chorionic villous sampling (n=113) and placenta (n=47). Differential expression analysis and mRNA target analysis were also examined. Sequencing identified 2,503 unique mature miRNAs expressed in each trimester. Of these, 13 significantly sexually dimorphic (FDR&lt;0.05) miRNAs were identified in the first trimester and 4 significantly sexually dimorphic miRNAs were identified in the third trimester, including one miRNA, hsa-miR-361-5p, expressed across gestation. All of these sexually dimorphic miRNAs were significantly upregulated in females compared to males. Pathways analysis with predicted targets suggests sex differences in cancer and inflammation-related pathways in the first trimester and inflammation and growth-related pathways in the third trimester. Differential expression analysis on sex-segregated data identified 613 miRNAs upregulated in female placentas and 636 miRNAs upregulated in male placentas across gestation (FDR&lt;0.05). In conclusion, fetal sex affects placental miRNA expression profiles and differentially expressed miRNAs may affect relevant downstream pathways, which may account for differences in pregnancy outcomes due to fetal sex. This work provides an expression atlas to direct functional studies investigating placental sex differences.

Human placenta makes extracellular glutathione peroxidase and secretes it into maternal circulation

1994 ◽  
Vol 267 (1) ◽  
pp. E68-E76 ◽  
Author(s):  
N. Avissar ◽  
C. Eisenmann ◽  
J. G. Breen ◽  
S. Horowitz ◽  
R. K. Miller ◽  
...  
Keyword(s):  
Endothelial Cells ◽  
Glutathione Peroxidase ◽  
Human Placenta ◽  
Stromal Cells ◽  
First Trimester ◽  
Full Term ◽  
Third Trimester ◽  
Maternal Circulation ◽  
In Situ Hybridizations

Extracellular glutathione peroxidase (eGPX) is a selenoglycoprotein distinct from cellular glutathione peroxidase (cGPX). The cDNA for eGPX has recently been cloned from human placenta. To determine whether human placenta makes both cGPX and eGPX and secretes eGPX, we used specific immunoprecipitations of 75Se metabolically labeled proteins from full-term placental explants in culture and perfused placental lobules. Placental explants and metabolically active, dually perfused placental lobules synthesized and contained both cGPX and eGPX and secreted eGPX. Perfused tissue secreted eGPX into the maternal but not into the fetal perfusate. In situ hybridizations using antisense and sense eGPX riboprobes were performed on sections of first-, second-, and third-trimester placentas. In the first-trimester placenta, transcripts were localized predominantly to cytotrophoblast cells, whereas in the full-term placenta syncytiotrophoblast cells and stromal cells but not fetal endothelial cells expressed eGPX mRNA. It is concluded that human placenta synthesizes both cGPX and eGPX and secretes eGPX into the maternal circulation, consistent with the location of the eGPX mRNA.

scholarly journals Human Placenta MicroRNA Differences Between First and Third Trimester

2021 ◽  
Vol 5 (Supplement_1) ◽  
pp. A504-A505
Author(s):  
Tania L Gonzalez ◽  
Laura E Eisman ◽  
Nikhil Joshi ◽  
Amy E Flowers ◽  
Di Wu ◽  
...  
Keyword(s):  
Human Placenta ◽  
Mirna Expression ◽  
Chorionic Villus ◽  
First Trimester ◽  
Prognostic Indicators ◽  
Chorionic Villus Sampling ◽  
Growth Factor Signaling ◽  
Third Trimester ◽  
Functional Studies ◽  
Mirna Clusters

Abstract MiRNAs are widespread regulators of gene expression, and altered miRNA expression in the placenta may be involved in abnormal placentation and related pregnancy-associated diseases. It is essential to understand miRNA expression changes across gestation before miRNAs can be used as biomarkers or prognostic indicators. Using next-generation sequencing, we characterize the normative human placenta miRNA transcriptome in both the first and third trimester using leftover chorionic villus sampling tissue from prenatal tests (N=113) as well as placentae collected at delivery (N=47). We identified 2503 miRNAs, including 1647 with stable expression across gestation (p&gt;=0.05). There were 775 significantly differentially expressed miRNAs (FDR&lt;0.05), with 402 upregulated in first trimester and 373 upregulated in third trimester. We also examine expression of the placenta-specific miRNA clusters on chromosomes 14 and 19 which are important in pregnancy. We identified predicted targets with high confidence scores or experimental verification, then used these to identify enriched canonical biological pathways. Our study identified canonical pathways consistently targeted across gestation, including pathways regulating senescence, proliferation and growth factor signaling. We also identified differentially impacted pathways, including growth- and immune-mediated pathways. This work provides a rich atlas to direct functional studies investigating the epigenetic differences in first and third trimester placentae. We gratefully acknowledge support from the Eunice Kennedy Shriver National Institute of Child Health and Human Development (R01HD091773) and the Ruth L. Kirschstein National Research Service Award (T32DK007770) of the National Institutes of Health.

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