ijms-logo

Journal Browser

Journal Browser

Special Issue "Molecular Aspects of Inflammation in Pregnancy 2.0"

A special issue of International Journal of Molecular Sciences (ISSN 1422-0067). This special issue belongs to the section "Molecular Immunology".

Deadline for manuscript submissions: 25 July 2022 | Viewed by 5008

Special Issue Editor

Dr. Martin Gauster
E-Mail Website
Guest Editor
Division of Cell Biology, Histology and Embryology, Gottfried Schatz Research Center for Cell Signaling, Metabolism and Aging, Medical University of Graz, Neue Stiftingtalstraße 6/II, 8010 Graz, Austria
Interests: placenta development; trophoblast differentiation; cytokines and chemokines in placenta physiology; maternal–fetal cross-talk
Special Issues, Collections and Topics in MDPI journals

Special Issue Information

Dear Colleagues,

This Special Issue is a continuation of our previous Special Issue "Molecular Aspects of Inflammation in Pregnancy" (https://www.mdpi.com/journal/ijms/special_issues/pregnancy_inflammation).

Uncomplicated human pregnancy relies on a fine-balanced synergistic crosstalk of inflammatory and immune-modulating factors. Hence, maternal immune functions need to adapt to different stages of pregnancy, which are characterized by unique inflammatory environments. Unrestrained and exaggerated inflammation in human pregnancy is directly associated with the increased mortality and morbidity of the mother and offspring. The major complications of pregnancy, including pre-eclampsia, fetal growth restriction, gestational diabetes and/or obesity ("diabesity"), preterm labor, and miscarriage, have been associated with an abnormal maternal inflammatory response, both systemically and locally at the placenta. Although much progress is being made in understanding the molecular basis of these disorders, a significant knowledge gap still exists, in identifying important molecular targets and pathways, which could eventually contribute to the development of new drug therapies and the improvement of pregnancy outcomes.

This Special Issue, "Molecular Aspects of Inflammation in Pregnancy 2.0", will cover a selection of recent research topics and current review articles related to molecular mechanisms, leading to abberant inflammatory processes in human pregnancy complications. Experimental papers, up-to-date review articles, and commentaries are all welcome.

Dr. Martin Gauster
Guest Editor

Manuscript Submission Information

Manuscripts should be submitted online at www.mdpi.com by registering and logging in to this website. Once you are registered, click here to go to the submission form. Manuscripts can be submitted until the deadline. All submissions that pass pre-check are peer-reviewed. Accepted papers will be published continuously in the journal (as soon as accepted) and will be listed together on the special issue website. Research articles, review articles as well as short communications are invited. For planned papers, a title and short abstract (about 100 words) can be sent to the Editorial Office for announcement on this website.

Submitted manuscripts should not have been published previously, nor be under consideration for publication elsewhere (except conference proceedings papers). All manuscripts are thoroughly refereed through a single-blind peer-review process. A guide for authors and other relevant information for submission of manuscripts is available on the Instructions for Authors page. International Journal of Molecular Sciences is an international peer-reviewed open access semimonthly journal published by MDPI.

Please visit the Instructions for Authors page before submitting a manuscript. There is an Article Processing Charge (APC) for publication in this open access journal. For details about the APC please see here. Submitted papers should be well formatted and use good English. Authors may use MDPI's English editing service prior to publication or during author revisions.

Keywords

  • Pregnancy
  • Inflammation
  • Placenta
  • Pre-eclampsia
  • Fetal growth restriction
  • Gestational diabetes
  • Gestational hypertension
  • Preterm labor

Published Papers (6 papers)

Order results
Result details
Select all
Export citation of selected articles as:

Research

Jump to: Review, Other

Article
Transient Hyperglycemia and Hypoxia Induce Memory Effects in AngiomiR Expression Profiles of Feto-Placental Endothelial Cells
Int. J. Mol. Sci. 2021, 22(24), 13378; https://doi.org/10.3390/ijms222413378 - 13 Dec 2021
Cited by 1 | Viewed by 692
Abstract
Gestational diabetes (GDM) and preeclampsia (PE) are associated with fetal hyperglycemia, fetal hypoxia, or both. These adverse conditions may compromise fetal and placental endothelial cells. In fact, GDM and PE affect feto-placental endothelial function and also program endothelial function and cardiovascular disease risk [...] Read more.
Gestational diabetes (GDM) and preeclampsia (PE) are associated with fetal hyperglycemia, fetal hypoxia, or both. These adverse conditions may compromise fetal and placental endothelial cells. In fact, GDM and PE affect feto-placental endothelial function and also program endothelial function and cardiovascular disease risk of the offspring in the long-term. MicroRNAs are short, non-coding RNAs that regulate protein translation and fine tune biological processes. A group of microRNAs termed angiomiRs is particularly involved in the regulation of endothelial function. We hypothesized that transient hyperglycemia and hypoxia may alter angiomiR expression in feto-placental endothelial cells (fpEC). Thus, we isolated primary fpEC after normal, uncomplicated pregnancy, and induced hyperglycemia (25 mM) and hypoxia (6.5%) for 72 h, followed by reversal to normal conditions for another 72 h. Current vs. transient effects on angiomiR profiles were analyzed by RT-qPCR and subjected to miRNA pathway analyses using DIANA miRPath, MIENTURNET and miRPathDB. Both current and transient hypoxia affected angiomiR profile stronger than current and transient hyperglycemia. Both stimuli altered more angiomiRs transiently, i.e., followed by 72 h culture at control conditions. Pathway analysis revealed that hypoxia significantly altered the pathway ‘Proteoglycans in cancer’. Transient hypoxia specifically affected miRNAs related to ‘adherens junction’. Our data reveal that hyperglycemia and hypoxia induce memory effects on angiomiR expression in fpEC. Such memory effects may contribute to long-term adaption and maladaption to hyperglycemia and hypoxia. Full article
(This article belongs to the Special Issue Molecular Aspects of Inflammation in Pregnancy 2.0)
Show Figures

Figure 1

Communication
Type 1 Diabetes Mellitus and the First Trimester Placenta: Hyperglycemia-Induced Effects on Trophoblast Proliferation, Cell Cycle Regulators, and Invasion
Int. J. Mol. Sci. 2021, 22(20), 10989; https://doi.org/10.3390/ijms222010989 - 12 Oct 2021
Viewed by 485
Abstract
Type 1 diabetes mellitus (T1DM) is associated with reduced fetal growth in early pregnancy, but a contributing role of the placenta has remained elusive. Thus, we investigated whether T1DM alters placental development in the first trimester. Using a protein array, the level of [...] Read more.
Type 1 diabetes mellitus (T1DM) is associated with reduced fetal growth in early pregnancy, but a contributing role of the placenta has remained elusive. Thus, we investigated whether T1DM alters placental development in the first trimester. Using a protein array, the level of 60 cell-cycle-related proteins was determined in human first trimester placental tissue (gestational week 5–11) from control (n = 11) and T1DM pregnancies (n = 12). Primary trophoblasts (gestational week 7–12, n = 32) were incubated in the absence (control) or presence of hyperglycemia (25 mM D-glucose) and hyperosmolarity (5.5 mM D-glucose + 19.5 mM D-mannitol). We quantified the number of viable and dead trophoblasts (CASY Counter) and assessed cell cycle distribution (FACS) and trophoblast invasion using a transwell assay. T1DM was associated with a significant (p < 0.05) downregulation of Ki67 (−26%), chk1 (−25%), and p73 (−26%). The number of viable trophoblasts was reduced under hyperglycemia (−23%) and hyperosmolarity (−18%), whereas trophoblast invasion was increased only under hyperglycemia (+6%). Trophoblast cell death and cell cycle distribution remained unaffected. Collectively, our data demonstrate that hyperglycemia decreases trophoblast proliferation as a potential contributing factor to the reduced placental growth in T1DM in vivo. Full article
(This article belongs to the Special Issue Molecular Aspects of Inflammation in Pregnancy 2.0)
Show Figures

Figure 1

Article
Maternal C-Peptide and Insulin Sensitivity, but Not BMI, Associate with Fatty Acids in the First Trimester of Pregnancy
Int. J. Mol. Sci. 2021, 22(19), 10422; https://doi.org/10.3390/ijms221910422 - 27 Sep 2021
Cited by 1 | Viewed by 640
Abstract
Maternal obesity in pregnancy is a pro-inflammatory condition exposing the fetus to an adverse environment. Here, we tested associations of maternal obesity (primary exposures: BMI, leptin) and metabolic parameters (secondary exposures: glucose, C-peptide, and insulin sensitivity) with total serum concentrations of fatty acids [...] Read more.
Maternal obesity in pregnancy is a pro-inflammatory condition exposing the fetus to an adverse environment. Here, we tested associations of maternal obesity (primary exposures: BMI, leptin) and metabolic parameters (secondary exposures: glucose, C-peptide, and insulin sensitivity) with total serum concentrations of fatty acids in the first trimester of human pregnancy. This cross-sectional study included 123 non-smoking women with singleton pregnancy. In maternal serum, cotinine, leptin, and C-peptide (ELISA), glucose (hexokinase-based test) and fatty acids (gas chromatography) were quantified, and the insulin sensitivity index (ISHOMA) was calculated. Concentrations of fatty acid classes and total fatty acids did not differ between BMI or leptin categories. However, n-3 polyunsaturated fatty acids (PUFA) were decreased in the category with the highest C-peptide concentration (n-3 PUFA: CI −35.82–−6.28, p < 0.006) and in the lowest ISHOMA category (n-3 PUFA: CI −36.48–−5.61, p < 0.008). In a subcohort, in which fetal sex was determined (RT-qPCR of placental tissue), C-peptide was significantly associated with docosahexaenoic acid (DHA) in mothers bearing a female (n = 46), but not male (n = 37) fetus. In conclusion, pregnant women with high fasting C-peptide and low ISHOMA had decreased n-3 PUFA, and DHA was lower with higher C-peptide only in mothers bearing a female fetus. Full article
(This article belongs to the Special Issue Molecular Aspects of Inflammation in Pregnancy 2.0)
Show Figures

Figure 1

Communication
Placental Complement Activation in Fetal and Neonatal Alloimmune Thrombocytopenia: An Observational Study
Int. J. Mol. Sci. 2021, 22(13), 6763; https://doi.org/10.3390/ijms22136763 - 23 Jun 2021
Viewed by 1147
Abstract
Fetal and neonatal alloimmune thrombocytopenia (FNAIT) is a disease that causes thrombocytopenia and a risk of bleeding in the (unborn) child that result from maternal alloantibodies directed against fetal, paternally inherited, human platelet antigens (HPA). It is hypothesized that these alloantibodies can also [...] Read more.
Fetal and neonatal alloimmune thrombocytopenia (FNAIT) is a disease that causes thrombocytopenia and a risk of bleeding in the (unborn) child that result from maternal alloantibodies directed against fetal, paternally inherited, human platelet antigens (HPA). It is hypothesized that these alloantibodies can also bind to the placenta, causing placental damage. This study aims to explore signs of antibody-mediated placental damage in FNAIT. We performed a retrospective study that included pregnant women, their newborns, and placentas. It comprised 23 FNAIT cases, of which nine were newly diagnosed (14 samples) and 14 were antenatally treated with intravenous immune globulins (IVIg) (21 samples), and 20 controls, of which 10 had anti-HLA-class I antibodies. Clinical information was collected from medical records. Placental samples were stained for complement activation markers (C1q, C4d, SC5b-9, and mannose-binding lectin) using immunohistochemistry. Histopathology was examined according to the Amsterdam criteria. A higher degree of C4d deposition was present in the newly diagnosed FNAIT cases (10/14 samples), as compared to the IVIg-treated FNAIT cases (2/21 samples, p = 0.002) and anti-HLA-negative controls (3/20 samples, p = 0.006). A histopathological examination showed delayed maturation in four (44%) placentas in the newly diagnosed FNAIT cases, five (36%) in the IVIg-treated FNAIT cases, and one in the controls (NS). C4d deposition at the syncytiotrophoblast was present in combination with low-grade villitis of unknown etiology in three newly diagnosed FNAIT cases that were born SGA. We conclude that a higher degree of classical pathway-induced complement activation is present in placentas from pregnancies with untreated FNAIT. This may affect placental function and fetal growth. Full article
(This article belongs to the Special Issue Molecular Aspects of Inflammation in Pregnancy 2.0)
Show Figures

Figure 1

Review

Jump to: Research, Other

Review
Placental Endocrine Activity: Adaptation and Disruption of Maternal Glucose Metabolism in Pregnancy and the Influence of Fetal Sex
Int. J. Mol. Sci. 2021, 22(23), 12722; https://doi.org/10.3390/ijms222312722 - 24 Nov 2021
Cited by 1 | Viewed by 752
Abstract
The placenta is an endocrine fetal organ, which secretes a plethora of steroid- and proteo-hormones, metabolic proteins, growth factors, and cytokines in order to adapt maternal physiology to pregnancy. Central to the growth of the fetus is the supply with nutrients, foremost with [...] Read more.
The placenta is an endocrine fetal organ, which secretes a plethora of steroid- and proteo-hormones, metabolic proteins, growth factors, and cytokines in order to adapt maternal physiology to pregnancy. Central to the growth of the fetus is the supply with nutrients, foremost with glucose. Therefore, during pregnancy, maternal insulin resistance arises, which elevates maternal blood glucose levels, and consequently ensures an adequate glucose supply for the developing fetus. At the same time, maternal β-cell mass and function increase to compensate for the higher insulin demand. These adaptations are also regulated by the endocrine function of the placenta. Excessive insulin resistance or the inability to increase insulin production accordingly disrupts physiological modulation of pregnancy mediated glucose metabolism and may cause maternal gestational diabetes (GDM). A growing body of evidence suggests that this adaptation of maternal glucose metabolism differs between pregnancies carrying a girl vs. pregnancies carrying a boy. Moreover, the risk of developing GDM differs depending on the sex of the fetus. Sex differences in placenta derived hormones and bioactive proteins, which adapt and modulate maternal glucose metabolism, are likely to contribute to this sexual dimorphism. This review provides an overview on the adaptation and maladaptation of maternal glucose metabolism by placenta-derived factors, and highlights sex differences in this regulatory network. Full article
(This article belongs to the Special Issue Molecular Aspects of Inflammation in Pregnancy 2.0)
Show Figures

Figure 1

Other

Jump to: Research, Review

Case Report
One-Sided Chronic Intervillositis of Unknown Etiology in Dizygotic Twins: A Description of 3 Cases
Int. J. Mol. Sci. 2021, 22(9), 4786; https://doi.org/10.3390/ijms22094786 - 30 Apr 2021
Cited by 1 | Viewed by 608
Abstract
Chronic intervillositis of unknown etiology (CIUE) is a rare, poorly understood, histopathological diagnosis of the placenta that is frequently accompanied by adverse pregnancy outcomes including miscarriage, fetal growth restriction, and intrauterine fetal death. CIUE is thought to have an immunologically driven pathophysiology and [...] Read more.
Chronic intervillositis of unknown etiology (CIUE) is a rare, poorly understood, histopathological diagnosis of the placenta that is frequently accompanied by adverse pregnancy outcomes including miscarriage, fetal growth restriction, and intrauterine fetal death. CIUE is thought to have an immunologically driven pathophysiology and may be related to human leukocyte antigen mismatches between the mother and the fetus. Dizygotic twins with one-sided CIUE provide an interesting context to study the influence of immunogenetic differences in such cases. The main immune-cell subsets were investigated using immunohistochemistry. We identified three dizygotic twin pregnancies in which CIUE was present in only one of the two placentas. Two of the pregnancies ended in term delivery and one ended in preterm delivery. Presence of CIUE was correlated with lower placental weight and lower birthweight. Relative number of CD68, CD56, CD20, and CD3 positive cells were comparable between co-twins. The presence of one-sided CIUE in dizygotic twin pregnancy was associated with selective growth restriction in the affected twin. This suggests a unique fetal immunogenetic contribution to the pathogenesis of CIUE. Further study of dizygotic and monozygotic placentas affected by CIUE could identify new insights into its pathophysiology and into the field of reproductive immunology. Full article
(This article belongs to the Special Issue Molecular Aspects of Inflammation in Pregnancy 2.0)
Show Figures

Figure 1

Back to TopTop