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Molecular Pathogenesis and Treatment of Pregnancy Complications

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A special issue of International Journal of Molecular Sciences (ISSN 1422-0067). This special issue belongs to the section "Molecular Pathology, Diagnostics, and Therapeutics".

Deadline for manuscript submissions: 25 September 2024 | Viewed by 3106

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Special Issue Editors

Dr. Radzisław Mierzyński

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Guest Editor

Chair and Department of Obstetrics and Perinatology, Medical University of Lublin, 20-954 Lublin, Poland
Interests: maternal and fetal medicine; obesity; metabolic syndrome; adipokines; maternal nutrition; hypertension; preeclampsia; ultrasound in obstetrics; perinatal outcome

Dr. Elżbieta Poniedziałek-Czajkowska

E-Mail Website
Guest Editor

Chair and Department of Obstetrics and Perinatology, Medical University of Lublin, 20-954 Lublin, Poland
Interests: maternal and fetal medicine; obesity; metabolic syndrome; adipokines; hypertension; preeclampsia; preterm labor; obstetric emergency; perinatal outcome
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Special Issue Information

Dear Colleagues,

We are honored to present this Special Issue entitled "Molecular Pathogenesis and Treatment of Pregnancy Complications". It aims to present high-quality scientific articles (original research articles or comprehensive/systematic review papers) presenting the latest achievements and research directions in the field of pregnancy complications.

Pregnancy is a unique period in which attention is focused simultaneously on two people: the mother and the developing baby. The health of the pregnant mother during the pre-pregnancy period is one of the necessary conditions for the proper development of the fetus and affects the further development of the child after birth. An understanding of the molecular mechanisms associated with the initiation and onset of severe pregnancy-related complications enables for the identification of potential biomarkers for early stratification of at-risk patients. Pregnancy-related complications may also affect the occurrence of metabolic, cardiovascular, cerebrovascular, renal and other diseases in the later life of mothers and their offspring. The currently observed progress in perinatal medicine in the field of basic sciences has allowed us to understand to a greater degree the impact of maternal factors on the development of the fetus. Additionally, the development of trials has meant that we can now create the optimal conditions for the development of the fetus through the prevention and treatment of diseases in the mother.

The aim of this Special Issue is to provide an overview of the latest research on the molecular mechanisms involved in pregnancy-related complications. In the hope of creating a multidisciplinary platform for scientific exchange, we invite all researchers interested in maternal health to share their research results.

Dr. Radzisław Mierzyński
Dr. Elżbieta Poniedziałek-Czajkowska
Guest Editors

Manuscript Submission Information

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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

preterm delivery
intraamniotic infection
preeclampsia
hypertension
metabolic syndrome
maternal health
prematurity

Published Papers (4 papers)

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Research

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14 pages, 1652 KiB

Open AccessArticle

Fetal Hypoglycemia Induced by Placental SLC2A3-RNA Interference Alters Fetal Pancreas Development and Transcriptome at Mid-Gestation

by Victoria C. Kennedy, Cameron S. Lynch, Amelia R. Tanner, Quinton A. Winger, Ahmed Gad, Paul J. Rozance and Russell V. Anthony

Int. J. Mol. Sci. 2024, 25(9), 4780; https://doi.org/10.3390/ijms25094780 - 27 Apr 2024

Viewed by 232

Abstract

Glucose, the primary energy substrate for fetal oxidative processes and growth, is transferred from maternal to fetal circulation down a concentration gradient by placental facilitative glucose transporters. In sheep, SLC2A1 and SLC2A3 are the primary transporters available in the placental epithelium, with SLC2A3 located on the maternal-facing apical trophoblast membrane and SLC2A1 located on the fetal-facing basolateral trophoblast membrane. We have previously reported that impaired placental SLC2A3 glucose transport resulted in smaller, hypoglycemic fetuses with reduced umbilical artery insulin and glucagon concentrations, in addition to diminished pancreas weights. These findings led us to subject RNA derived from SLC2A3-RNAi (RNA interference) and NTS-RNAi (non-targeting sequence) fetal pancreases to qPCR followed by transcriptomic analysis. We identified a total of 771 differentially expressed genes (DEGs). Upregulated pathways were associated with fat digestion and absorption, particularly fatty acid transport, lipid metabolism, and cholesterol biosynthesis, suggesting a potential switch in energetic substrates due to hypoglycemia. Pathways related to molecular transport and cell signaling in addition to pathways influencing growth and metabolism of the developing pancreas were also impacted. A few genes directly related to gluconeogenesis were also differentially expressed. Our results suggest that fetal hypoglycemia during the first half of gestation impacts fetal pancreas development and function that is not limited to β cell activity. Full article

(This article belongs to the Special Issue Molecular Pathogenesis and Treatment of Pregnancy Complications)

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11 pages, 1290 KiB

Open AccessArticle

Identification of Short-Chain Fatty Acids for Predicting Preterm Birth in Cervicovaginal Fluid Using Mass Spectrometry

by Young-Min Hur, Eun-Jin Kwon, Young-Ah You, Sunwha Park, Soo-Min Kim, Gain Lee, Yoon-Young Go and Young-Ju Kim

Int. J. Mol. Sci. 2024, 25(6), 3396; https://doi.org/10.3390/ijms25063396 - 17 Mar 2024

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Abstract

Preterm birth (PTB) refers to delivery before 37 weeks of gestation. Premature neonates exhibit higher neonatal morbidity and mortality rates than term neonates; therefore, predicting and preventing PTB are important. In this study, we investigated the potential of using short-chain fatty acid (SCFA) levels, specific vaginal microbiota-derived metabolites, as a biomarker in predicting PTB using gas chromatography/mass spectrometry. Cervicovaginal fluid (CVF) was collected from 89 pregnant women (29 cases of PTB vs. 60 controls) without evidence of other clinical infections, and SCFA levels were measured. Furthermore, the PTB group was divided into two subgroups based on birth timing after CVF sampling: delivery ≤ 2 days after sampling (n = 10) and ≥2 days after sampling (n = 19). The concentrations of propionic acid, isobutyric acid, butyric acid, valeric acid, hexanoic acid, and heptanoic acid were significantly higher in the PTB group than in the term birth (TB) group (p < 0.05). In particular, the concentrations of propionic acid, isobutyric acid, hexanoic acid, and heptanoic acid were continuously higher in the PTB group than in the TB group (p < 0.05). In the delivery ≤ 2 days after sampling group, the propionic acid, isobutyric acid, hexanoic acid, and heptanoic acid levels were significantly higher than those in the other groups (p < 0.05). This study demonstrated a significant association between specific SCFAs and PTB. We propose these SCFAs as potential biomarkers for the prediction of PTB. Full article

(This article belongs to the Special Issue Molecular Pathogenesis and Treatment of Pregnancy Complications)

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Review

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28 pages, 1298 KiB

Open AccessReview

Neurodevelopmental Disruptions in Children of Preeclamptic Mothers: Pathophysiological Mechanisms and Consequences

by Andrea González-Rojas and Martina Valencia-Narbona

Int. J. Mol. Sci. 2024, 25(7), 3632; https://doi.org/10.3390/ijms25073632 - 24 Mar 2024

Viewed by 777

Abstract

Preeclampsia (PE) is a multisystem disorder characterized by elevated blood pressure in the mother, typically occurring after 20 weeks of gestation and posing risks to both maternal and fetal health. PE causes placental changes that can affect the fetus, particularly neurodevelopment. Its key pathophysiological mechanisms encompass hypoxia, vascular and angiogenic dysregulation, inflammation, neuronal and glial alterations, and disruptions in neuronal signaling. Animal models indicate that PE is correlated with neurodevelopmental alterations and cognitive dysfunctions in offspring and in humans, an association between PE and conditions such as cerebral palsy, autism spectrum disorder, attention deficit hyperactivity disorder, and sexual dimorphism has been observed. Considering the relevance for mothers and children, we conducted a narrative literature review to describe the relationships between the pathophysiological mechanisms behind neurodevelopmental alterations in the offspring of PE mothers, along with their potential consequences. Furthermore, we emphasize aspects pertinent to the prevention/treatment of PE in pregnant mothers and alterations observed in their offspring. The present narrative review offers a current, complete, and exhaustive analysis of (i) the pathophysiological mechanisms that can affect neurodevelopment in the children of PE mothers, (ii) the relationship between PE and neurological alterations in offspring, and (iii) the prevention/treatment of PE. Full article

(This article belongs to the Special Issue Molecular Pathogenesis and Treatment of Pregnancy Complications)

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Graphical abstract

20 pages, 1368 KiB

Open AccessReview

The Role of the FGF19 Family in the Pathogenesis of Gestational Diabetes: A Narrative Review

by Agata Sadowska, Elżbieta Poniedziałek-Czajkowska and Radzisław Mierzyński

Int. J. Mol. Sci. 2023, 24(24), 17298; https://doi.org/10.3390/ijms242417298 - 09 Dec 2023

Viewed by 1040

Abstract

Gestational diabetes mellitus (GDM) is one of the most common pregnancy complications. Understanding the pathogenesis and appropriate diagnosis of GDM enables the implementation of early interventions during pregnancy that reduce the risk of maternal and fetal complications. At the same time, it provides opportunities to prevent diabetes, metabolic syndrome, and cardiovascular diseases in women with GDM and their offspring in the future. Fibroblast growth factors (FGFs) represent a heterogeneous family of signaling proteins which play a vital role in cell proliferation and differentiation, repair of damaged tissues, wound healing, angiogenesis, and mitogenesis and also affect the regulation of carbohydrate, lipid, and hormone metabolism. Abnormalities in the signaling function of FGFs may lead to numerous pathological conditions, including metabolic diseases. The FGF19 subfamily, also known as atypical FGFs, which includes FGF19, FGF21, and FGF23, is essential in regulating metabolic homeostasis and acts as a hormone while entering the systemic circulation. Many studies have pointed to the involvement of the FGF19 subfamily in the pathogenesis of metabolic diseases, including GDM, although the results are inconclusive. FGF19 and FGF21 are thought to be associated with insulin resistance, an essential element in the pathogenesis of GDM. FGF21 may influence placental metabolism and thus contribute to fetal growth and metabolism regulation. The observed relationship between FGF21 and increased birth weight could suggest a potential role for FGF21 in predicting future metabolic abnormalities in children born to women with GDM. In this group of patients, different mechanisms may contribute to an increased risk of cardiovascular diseases in women in later life, and FGF23 appears to be their promising early predictor. This study aims to present a comprehensive review of the FGF19 subfamily, emphasizing its role in GDM and predicting its long-term metabolic consequences for mothers and their offspring. Full article

(This article belongs to the Special Issue Molecular Pathogenesis and Treatment of Pregnancy Complications)

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