Maternal Obesity Influences Placental Nutrient Transport, Inflammatory Status, and Morphology in Human Term Placenta

2020 ◽  
Author(s):  
Perrine Nogues ◽  
Esther Dos Santos ◽  
Anne Couturier-Tarrade ◽  
Paul Berveiller ◽  
Lucie Arnould ◽  
...  
Keyword(s):  
Maternal Obesity ◽  
Immune Cell ◽  
Hormone Secretion ◽  
Nutrient Transport ◽  
Placental Tissue ◽  
First Trimester ◽  
Control Group ◽  
Placental Development ◽  
Cell Content ◽  
Inflammatory Status

Abstract Context Maternal obesity has a significant impact on placental development. However, this impact on the placenta’s structure and function (ie, nutrient transport and hormone and cytokine production) is a controversial subject. Objective We hypothesized that maternal obesity is associated with morphologic, secretory, and nutrient-related changes and elevated levels of inflammation in the placenta. Design We collected samples of placental tissue from 2 well-defined groups of pregnant women from 2017 to 2019. We compared the 2 groups regarding placental cytokine and hormone secretion, immune cell content, morphology, and placental nutrient transporter expressions. Setting Placenta were collected after caesarean section performed by experienced clinicians at Centre Hospitalier Intercommunal (CHI) of Poissy-Saint-Germain-en-Laye. Patients The main inclusion criteria were an age between 27 and 37 years old, no complications of pregnancy, and a first-trimester body mass index of 18–25 kg/m2 for the nonobese (control) group and 30–40 kg/m2 for the obese group. Results In contrast to our starting hypothesis, we observed that maternal obesity was associated with (1) lower placental IL-6 expression and macrophage/leukocyte infiltration, (2) lower placental expression of GLUT1 and SNAT1-2, (3) a lower placental vessel density, and (4) lower levels of placental leptin and human chorionic gonadotropin production. Conclusion These results suggest that the placenta is a plastic organ and could optimize fetal growth. A better understanding of placental adaptation is required because these changes may partly determine the fetal outcome in cases of maternal obesity.

scholarly journals Prostaglandin E2 receptor 3 signaling is induced in placentas with unexplained recurrent pregnancy losses

2018 ◽  
Vol 7 (5) ◽  
pp. 749-761 ◽  
Author(s):  
Yao Ye ◽  
Aurelia Vattai ◽  
Nina Ditsch ◽  
Christina Kuhn ◽  
Martina Rahmeh ◽  
...  
Keyword(s):  
Hormone Secretion ◽  
First Trimester ◽  
Control Group ◽  
Prostaglandin E ◽  
Inflammatory Reactions ◽  
Inflammatory Microenvironment ◽  
Immune Balance ◽  
Beta Hcg ◽  
Recurrent Pregnancy Losses

Although an inflammatory microenvironment is required for successful implantation, an inflammatory overreaction is one of the causes of unexplained recurrent pregnancy losses (uRPL). Prostaglandin E2 (PGE2) plays a pivotal role in regulating immune balance during early pregnancy, and it can stimulate inflammatory reactions via prostaglandin E2 receptor 3 (EP3). However, the role of PGE2 receptor signaling in the uRPL remains unknown. We aimed to investigate whether EP3 signaling is involved in the mechanism of uRPL. Via immunohistochemistry we could show that the expression of cyclooxygenase-2, EP3 and G protein alpha inhibitor 1 (Gi1) was enhanced in the decidua of the uRPL group in comparison to the control group in first-trimester placentas. In vitro, we demonstrated that sulprostone (an EP1/EP3 agonist) inhibited the secretion of beta-hCG and progesterone in JEG-3 cells and the secretion of beta-hCG in HTR-8/SVneo cells while it induced the expression of plasminogen activator inhibitor type 1 in JEG-3 cells. In addition, PGE2/sulprostone was able to stimulate the expression of Gi1, phosphorylated-extracellular signal-regulated kinases 1/2 (p-ERK1/2) and p53. L-798,106 (an EP3-specific antagonist) suppressed the expression of EP3 and p-ERK1/2 without affecting the secretion of beta-hCG. Elevated activation of EP3 signaling in first-trimester placentas plays an important role in regulating the inflammatory microenvironment, the hormone secretion of extravillous trophoblasts and the remodeling of extracellular matrix in the fetal-maternal interface. L-798,106 might be a ‘potential therapeutic candidate’ for the treatment of uRPL.

scholarly journals IL-12 Gene Electrotransfer Triggers a Change in Immune Response within Mouse Tumors

Cancers ◽  
2018 ◽  
Vol 10 (12) ◽  
pp. 498 ◽  
Author(s):  
Guilan Shi ◽  
Chelsea Edelblute ◽  
Sezgi Arpag ◽  
Cathryn Lundberg ◽  
Richard Heller
Keyword(s):  
Immune Response ◽  
T Cells ◽  
Tumor Microenvironment ◽  
Mononuclear Cells ◽  
Immune Cell ◽  
Immune Memory ◽  
Control Group ◽  
Gene Electrotransfer ◽  
Cell Content ◽  
Peripheral Blood Mononuclear

Metastatic melanoma is an aggressive skin cancer with a relatively low survival rate. Immune-based therapies have shown promise in the treatment of melanoma, but overall complete response rates are still low. Previous studies have demonstrated the potential of plasmid IL-12 (pIL-12) delivered by gene electrotransfer (GET) to be an effective immunotherapy for melanoma. However, events occurring in the tumor microenvironment following delivery have not been delineated. Therefore, utilizing a B16F10 mouse melanoma model, we evaluated changes in the tumor microenvironment following delivery of pIL-12 using different GET parameters or injection of plasmid alone. The results revealed a unique immune cell composition after intratumoral injection of pIL-12 GET. The number of immune memory cells was markedly increased in pIL-12 GET melanoma groups compared to control group. This was validated using flow cytometry to analyze peripheral blood mononuclear cells as well as delineating immune cell content using immunohistochemistry. Significant differences in multiple cell types were observed, including CD8+ T cells, regulatory T cells and myeloid cells, which were induced to mount a CD8+PD1− T cells immune response. Taken together, these findings suggest a basic understanding of the sequence of immune activity following pIL-12 GET and also illuminates that adjuvant immunotherapy can have a positive influence on the host immune response to cancer.

scholarly journals Cell-specific characterization of the placental methylome

BMC Genomics ◽  
2021 ◽  
Vol 22 (1) ◽  
Author(s):  
Victor Yuan ◽  
Desmond Hui ◽  
Yifan Yin ◽  
Maria S. Peñaherrera ◽  
Alexander G. Beristain ◽  
...  
Keyword(s):  
Placental Tissue ◽  
Cell Types ◽  
First Trimester ◽  
R Package ◽  
Cell Populations ◽  
Placental Development ◽  
Methylation Array ◽  
Cell Composition ◽  
Distinct Cell ◽  
Hofbauer Cells

Abstract Background DNA methylation (DNAm) profiling has emerged as a powerful tool for characterizing the placental methylome. However, previous studies have focused primarily on whole placental tissue, which is a mixture of epigenetically distinct cell populations. Here, we present the first methylome-wide analysis of first trimester (n = 9) and term (n = 19) human placental samples of four cell populations: trophoblasts, Hofbauer cells, endothelial cells, and stromal cells, using the Illumina EPIC methylation array, which quantifies DNAm at > 850,000 CpGs. Results The most distinct DNAm profiles were those of placental trophoblasts, which are central to many pregnancy-essential functions, and Hofbauer cells, which are a rare fetal-derived macrophage population. Cell-specific DNAm occurs at functionally-relevant genes, including genes associated with placental development and preeclampsia. Known placental-specific methylation marks, such as those associated with genomic imprinting, repetitive element hypomethylation, and placental partially methylated domains, were found to be more pronounced in trophoblasts and often absent in Hofbauer cells. Lastly, we characterize the cell composition and cell-specific DNAm dynamics across gestation. Conclusions Our results provide a comprehensive analysis of DNAm in human placental cell types from first trimester and term pregnancies. This data will serve as a useful DNAm reference for future placental studies, and we provide access to this data via download from GEO (GSE159526), through interactive exploration from the web browser (https://robinsonlab.shinyapps.io/Placental_Methylome_Browser/), and through the R package planet, which allows estimation of cell composition directly from placental DNAm data.

scholarly journals Maternal Obesity Alters Placental Cell Cycle Regulators in the First Trimester of Human Pregnancy: New Insights for BRCA1

2020 ◽  
Vol 21 (2) ◽  
pp. 468 ◽  
Author(s):  
Denise Hoch ◽  
Martina Bachbauer ◽  
Caroline Pöchlauer ◽  
Francisco Algaba-Chueca ◽  
Veronika Tandl ◽  
...  
Keyword(s):  
Cell Cycle ◽  
Maternal Obesity ◽  
First Trimester ◽  
Cell Cycle Regulators ◽  
Placental Development ◽  
Cell Cycle Protein ◽  
Short Term Treatment ◽  
Placental Cell ◽  
Human Pregnancy ◽  
Wide Range

In the first trimester of pregnancy, placental development involves a wide range of cellular processes. These include trophoblast proliferation, fusion, and differentiation, which are dependent on tight cell cycle control. The intrauterine environment affects placental development, which also includes the trophoblast cell cycle. In this work, we focus on maternal obesity to assess whether an altered intrauterine milieu modulates expression and protein levels of placental cell cycle regulators in early human pregnancy. For this purpose, we use first trimester placental tissue from lean and obese women (gestational week 5+0–11+6, n = 58). Using a PCR panel, a cell cycle protein array, and STRING database analysis, we identify a network of cell cycle regulators increased by maternal obesity in which breast cancer 1 (BRCA1) is a central player. Immunostaining localizes BRCA1 predominantly to the villous and the extravillous cytotrophoblast. Obesity-driven BRCA1 upregulation is not able to be explained by DNA methylation (EPIC array) or by short-term treatment of chorionic villous explants at 2.5% oxygen with tumor necrosis factor α (TNF-α) (50 mg/mL), leptin (100 mg/mL), interleukin 6 (IL-6) (100 mg/mL), or high glucose (25 nM). Oxygen tension rises during the first trimester, but this change in vitro has no effect on BRCA1 (2.5% and 6.5% O2). We conclude that maternal obesity affects placental cell cycle regulation and speculate this may alter placental development.

scholarly journals Cell-specific Characterization of the Placental Methylome

2020 ◽  
Author(s):  
Victor Yuan ◽  
Desmond Hui ◽  
Yifan Yin ◽  
Maria Peñaherrera ◽  
Alexander Beristain ◽  
...  
Keyword(s):  
Placental Tissue ◽  
Cell Types ◽  
First Trimester ◽  
R Package ◽  
Cell Populations ◽  
Placental Development ◽  
Methylation Array ◽  
Cell Composition ◽  
Distinct Cell ◽  
Hofbauer Cells

Abstract Background: DNA methylation (DNAm) profiling has emerged as a powerful tool for characterizing the placental methylome. However, previous studies have focused primarily on whole placental tissue, which is a mixture of epigenetically distinct cell populations. Here, we present the first methylome-wide analysis of first trimester (n=9) and term (n=19) human placental samples of four cell populations: trophoblasts, Hofbauer cells, endothelial cells, and stromal cells, using the Illumina EPIC methylation array, which quantifies DNAm at >850,000 CpGs.Results: The most distinct DNAm profiles were those of placental trophoblasts, which are central to many pregnancy-essential functions, and Hofbauer cells, which are a rare fetal-derived macrophage population. Cell-specific DNAm occurs at functionally-relevant genes, including genes associated with placental development and preeclampsia. Known placental-specific methylation marks, such as those associated with genomic imprinting, repetitive element hypomethylation, and placental partially methylated domains, were found to be more pronounced in trophoblasts and often absent in Hofbauer cells. Lastly, we characterize the cell composition and cell-specific DNAm dynamics across gestation.Conclusions: Our results provide a comprehensive analysis of DNAm in human placental cell types from first trimester and term pregnancies. This data will serve as a useful DNAm reference for future placental studies, and we provide access to this data via download from GEO (GSE159526), through interactive exploration from the web browser (https://robinsonlab.shinyapps.io/Placental_Methylome_Browser/), and through the R package planet, which allows estimation of cell composition directly from placental DNAm data.

HORMONE ASSAYS DURING RECURRENT EXCESSIVE HAIRGROWTH IN PREGNANCY

1964 ◽  
Vol 45 (3) ◽  
pp. 447-456 ◽  
Author(s):  
Aarno Turunen ◽  
Sykkö Pesonen ◽  
Harry Zilliacus
Keyword(s):  
Placental Tissue ◽  
Normal Subjects ◽  
First Trimester ◽  
Control Group ◽  
Steroid Synthesis ◽  
Incubation Experiments ◽  
Before And After ◽  
Stimulation Tests ◽  
First Trimester Of Pregnancy ◽  
Hormone Excretion

ABSTRACT Three cases of recurrent excessive hairgrowth during pregnancy are described. The hormone excretion of two of these women was studied before and after stimulation tests. The patients received 40 IU of corticotrophin as an intravenous infusion and in addition a total of 3 mg fluorocortisone to produce suppression of the adrenals. Urinary steroids were determined before and during the stimulation tests. Four patients who were in the first trimester of pregnancy served as controls. After the legal termination of pregnancy incubation experiments with placental tissue were carried out to determine the ability of the placenta to convert the 17-OH-group of testosterone to the 17-keto-group. The results of these experiments were compared with those in normal subjects. In one case pregnancy had been legally terminated, and in the other the placenta was full-term. In both patients an increased 17-OH-progesterone secretion and some block in steroid synthesis were responsible for dysfunction. The excretion of total 17-ketosteroids, epiandrosterone and androsterone were higher in these patients than in the control group. In incubation experiments of placental tissue it was confirmed that the 17β-dehydrogenase activity of the patients was lower than in the control placenta. Hence, the inactivating capacity of testosterone was less than that of the control group. This phenomenon may be responsible for an increased level of testosterone in the plasma of the patients and of excessive hairgrowth during pregnancy. Of the six children born to the three mothers with recurrent excessive hairgrowth during pregnancy, three had severe congenital malformations, in one case of the heart and in two cases of the extremities.

scholarly journals Cell-specific Characterization of the Placental Methylome

2020 ◽  
Author(s):  
Victor Yuan ◽  
Desmond Hui ◽  
Yifan Yin ◽  
Maria Peñaherrera ◽  
Alexander Beristain ◽  
...  
Keyword(s):  
Placental Tissue ◽  
Cell Types ◽  
First Trimester ◽  
R Package ◽  
Cell Populations ◽  
Placental Development ◽  
Methylation Array ◽  
Cell Composition ◽  
Distinct Cell ◽  
Hofbauer Cells

Abstract Background: DNA methylation (DNAm) profiling has emerged as a powerful tool for characterizing the placental methylome. However, previous studies have focused primarily on whole placental tissue, which is a mixture of epigenetically distinct cell populations. Here, we present the first methylome-wide analysis of first trimester (n=9) and term (n=19) human placental samples of four cell populations: trophoblasts, Hofbauer cells, endothelial cells, and stromal cells, using the Illumina EPIC methylation array, which quantifies DNAm at >850,000 CpGs.Results: The most distinct DNAm profiles were those of placental trophoblasts, which are central to many pregnancy-essential functions, and Hofbauer cells, which are a rare fetal-derived macrophage population. Cell-specific DNAm occurs at functionally-relevant genes, including genes associated with placental development and preeclampsia. Known placental-specific methylation marks, such as those associated with genomic imprinting, repetitive element hypomethylation, and placental partially methylated domains, were found to be more pronounced in trophoblasts and often absent in Hofbauer cells. Lastly, we characterize the cell composition and cell-specific DNAm dynamics across gestation.Conclusions: Our results provide a comprehensive analysis of DNAm in human placental cell types from first trimester and term pregnancies. This data will serve as a useful DNAm reference for future placental studies, and we provide access to this data via download from dbGAP (phs002013.v1.p1), through interactive exploration from the web browser (https://robinsonlab.shinyapps.io/Placental_Methylome_Browser/), and through the R package planet, which allows estimation of cell composition directly from placental DNAm data.

scholarly journals Cell-specific Characterization of the Placental Methylome

2020 ◽  
Author(s):  
Victor Yuan ◽  
Desmond Hui ◽  
Yifan Yin ◽  
Maria Peñaherrera ◽  
Alexander Beristain ◽  
...  
Keyword(s):  
Placental Tissue ◽  
Cell Types ◽  
First Trimester ◽  
R Package ◽  
Cell Populations ◽  
Placental Development ◽  
Methylation Array ◽  
Cell Composition ◽  
Distinct Cell ◽  
Hofbauer Cells

Abstract Background DNA methylation (DNAm) profiling has emerged as a powerful tool for characterizing the placental methylome. However, previous studies have focused primarily on whole placental tissue, which is a mixture of epigenetically distinct cell populations. Here, we present the first methylome-wide analysis of first trimester (n = 9) and term (n = 19) human placental samples of four cell populations: trophoblasts, Hofbauer cells, endothelial cells, and stromal cells, using the Illumina EPIC methylation array, which quantifies DNAm at > 850,000 CpGs. Results The most distinct DNAm profiles were those of placental trophoblasts, which are central to many pregnancy-essential functions, and Hofbauer cells, which are a rare understudied macrophage population thought to derive from fetal monocytes. Cell-specific DNAm occurs at functionally-relevant genes, including genes associated with placental development and preeclampsia. Known placental-specific methylation marks, such as those associated with genomic imprinting, repetitive element hypomethylation, and placental partially methylated domains, were found to be more pronounced in trophoblasts and often absent in Hofbauer cells. Lastly, we characterize the cell composition and cell-specific DNAm dynamics across gestation. Conclusions Our results provide a comprehensive analysis of DNAm in human placental cell types from first trimester and term pregnancies. This data will serve as a useful DNAm reference for future placental studies, and we provide access to this data via download from dbGAP (phs002013.v1.p1), through interactive exploration from the web browser (https://robinsonlab.shinyapps.io/Placental_Methylome_Browser/), and through the R package planet, which allows estimation of cell composition directly from placental DNAm data.

FRACTIONAL DETERMINATIONS OF URINARY 17-KETOSTEROIDS IN HYPEREMESIS GRAVIDARUM

1962 ◽  
Vol 41 (1) ◽  
pp. 123-128 ◽  
Author(s):  
Pentti A. Järvinen ◽  
Sykkö Pesonen ◽  
Pirkko Väänänen
Keyword(s):  
Hyperemesis Gravidarum ◽  
First Trimester ◽  
Control Group ◽  
Before And After ◽  
Daily Urine ◽  
First Trimester Of Pregnancy ◽  
The Difference

ABSTRACT The fractional determination of 17-ketosteroids in the daily urine was performed in nine cases of hyperemesis gravidarum and in four control cases, in the first trimester of pregnancy both before and after corticotrophin administration. The excretion of total 17-KS is similar in the two groups. Only in the hyperemesis group does the excretion of total 17-KS increase significantly after corticotrophin administration. The fractional determination reveals no difference between the two groups of patients with regard to the values of the fractions U (unidentified 17-KS), A (androsterone) and Rest (11-oxygenated 17-KS). The excretion of dehydroepiandrosterone is significantly higher in the hyperemesis group than in the control group. The excretion of androstanolone seems to be lower in the hyperemesis group than in the control group, but the difference is not statistically significant. The differences in the correlation between dehydroepiandrosterone and androstanolone in the two groups is significant. The high excretion of dehydroepiandrosterone and low excretion of androstanolone in cases of hyperemesis gravidarum is a sign of adrenal dysfunction.

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