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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: closed (20 September 2024) | Viewed by 10103

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Special Issue Editor

Dr. Luis A. Silva-Lagos

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Guest Editor

Immunoendocrinology, Division of Medical Biology, Department of Pathology and Medical Biology, University Medical Center Groningen, Hanzeplein 1, 9713 GZ Groningen, The Netherlands
Interests: gestational diabetes mellitus; immunology; pregnancy

Special Issue Information

Dear Colleagues,

The Special Issue, titled "Molecular Mechanisms of Pregnancy Complications", aims to explore and analyze the complex biological processes and underlying molecular mechanisms that contribute to various pregnancy complications. We invite submissions that investigate the cellular and molecular causes or consequences of conditions or diseases associated with pregnancy, including gestational diabetes, preeclampsia, fetal growth restriction, and others. Our objective is to advance diagnosis, treatment, and maternal–fetal health outcomes by deepening our understanding of these disorders from both a fundamental scientific and clinical standpoint. We aim to focus on, but are not restricted to, interdisciplinary collaboration between experts in molecular biology, obstetrics, and gynecology through the acceptance of research articles, reviews, and studies that illuminate novel molecular pathways, biomarkers, and therapeutic approaches.

Dr. Luis A. Silva-Lagos
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.

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Published Papers (5 papers)

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Research

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16 pages, 1471 KiB

Open AccessArticle

Alteration in sB7-H4 Serum Levels and Placental Biomarker Expression after Therapeutic Plasma Exchange in Early-Onset Preeclampsia Patients

by Liyan Duan, Yuyang Ma, Beatrix Reisch, Elina Hadrovic, Pawel Mach, Rainer Kimmig, Michael Jahn, Angela Köninger, Antonella Iannaccone and Alexandra Gellhaus

Int. J. Mol. Sci. 2024, 25(20), 11082; https://doi.org/10.3390/ijms252011082 - 15 Oct 2024

Cited by 2 | Viewed by 1166

Abstract

Therapeutic plasma exchange (TPE) is a widely used treatment for numerous diseases including pregnancy-related conditions. Our prior study on 20 early-onset preeclampsia patients undergoing TPE revealed a significant extension in pregnancy duration and reduced serum levels of sFlt-1, sFlt-1/PlGF, and sEndoglin. Here, we investigated the impact of TPE on serum sB7-H4, an immunological checkpoint molecule, and placental proteins (Flt-1, Eng, B7-H4, iNOS, TNF-α) in TPE-treated early-onset preeclampsia patients (N = 12, 23 + 2–28 + 5 weeks), conventionally treated counterparts (N = 12, 23 + 5–30 weeks), and gestational age-matched controls (N = 8, 22 + 4–31 + 6 weeks). Immunoblotting, ELISA, and co-immunohistochemistry were used for biomarker analysis, including placental inflammation factors (iNOS, TNF-α). The results showed that TPE extended pregnancy by a median of 6.5 days in this cohort of early-onset preeclampsia. Serum sB7-H4, sFlt-1, and sEndoglin levels decreased, along with reduced expression of their membrane-bound proteins in placental tissue upon TPE treatment. Moreover, TPE-treated patients displayed reduced placental inflammation compared to preeclampsia patients receiving standard-of-care treatment. In conclusion, TPE may improve pregnancy outcomes in early-onset preeclampsia by lowering circulating levels of sB7-H4, sFlt-1, and sEndoglin, as well as reducing placental inflammation. This translational approach holds promise for enhancing placental function and extending gestation in high-risk pregnancies including very preterm PE or HELLP cases. Full article

(This article belongs to the Special Issue Molecular Mechanisms of Pregnancy Complications)

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13 pages, 1809 KiB

Open AccessArticle

Substance P Concentration in Gestational Diabetes and Excessive Gestational Weight Gain and Its Impact on Neonatal Anthropometry

by Magdalena Niebrzydowska-Tatus, Aleksandra Pełech, Katarzyna Bień, Anna K. Rekowska, Aleksandra Domańska, Żaneta Kimber-Trojnar, Bożena Leszczyńska-Gorzelak and Marcin Trojnar

Int. J. Mol. Sci. 2024, 25(7), 3759; https://doi.org/10.3390/ijms25073759 - 28 Mar 2024

Viewed by 1457

Abstract

Fetal programming is a process initiated by intrauterine conditions, leaving a lasting impact on the offspring’s health, whether they manifest immediately or later in life. It is believed that children born to mothers with gestational diabetes mellitus (GDM) and excessive gestational weight gain (EGWG) may be at an increased risk of developing type 2 diabetes mellitus (T2DM) and obesity later in their adult lives. Substance P is a neurotransmitter associated with obesity development and impairment of insulin signaling. Dysregulation of substance P could lead to several pregnancy pathologies, such as preeclampsia and preterm birth. Our study aimed to compare substance P concentrations in serum and umbilical cord blood in patients with GDM, EGWG, and healthy women with a family history of gestational weight gain. Substance P levels in umbilical cord blood were significantly higher in the GDM group compared to the EGWG and control groups. Substance P levels in serum and umbilical cord blood were positively correlated in all groups and the GDM group. A very interesting direction for future research is the relationship between the concentration of substance P in newborns of diabetic mothers and the occurrence of respiratory distress syndrome as a complication of impaired surfactant synthesis. To our knowledge, it is the first study assessing substance P concentration in GDM and EGWG patients. Full article

(This article belongs to the Special Issue Molecular Mechanisms of Pregnancy Complications)

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11 pages, 1260 KiB

Open AccessArticle

Inositol-Exchange Activity in Human Primordial Placenta

by Bence Géza Kovács, Gergely Asbóth, Dorina Supák, Balázs Mészáros, Tamás Marton, Nándor Ács, Sándor Valent and Zoltán Kukor

Int. J. Mol. Sci. 2024, 25(6), 3436; https://doi.org/10.3390/ijms25063436 - 19 Mar 2024

Viewed by 1312

Abstract

Human placenta is an intensively growing tissue. Phosphatidylinositol (PI) and its derivatives are part of the signaling pathway in the regulation of trophoblast cell differentiation. There are two different enzymes that take part in the direct PI synthesis: phosphatidylinositol synthase (PIS) and inositol exchange enzyme (IE). The presence of PIS is known in the human placenta, but IE activity has not been documented before. In our study, we describe the physiological properties of the two enzymes in vitro. PIS and IE were studied in different Mn²⁺ and Mg²⁺ concentrations that enabled us to separate the individual enzyme activities. Enzyme activity was measured by incorporation of 3[H]inositol in human primordial placenta tissue or microsomes. Optimal PIS activity was achieved between 0.5 and 2.0 mM Mn²⁺ concentration, but higher concentrations inhibit enzyme activity. In the presence of Mg²⁺, the enzyme activity increases continuously up to a concentration of 100 mM. PIS was inhibited by nucleoside di- and tri-phosphates. PI production increases between 0.1 and 10 mM Mn²⁺ concentration. The incorporation of [3H]inositol into PI increased by 57% when adding stabile GTP analog. The described novel pathway of inositol synthesis may provide an additional therapeutic approach of inositol supplementation before and during pregnancy. Full article

(This article belongs to the Special Issue Molecular Mechanisms of Pregnancy Complications)

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Review

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23 pages, 1189 KiB

Open AccessReview

The Role of the Vaginal and Endometrial Microbiomes in Infertility and Their Impact on Pregnancy Outcomes in Light of Recent Literature

by Bernadett Balla, Anett Illés, Bálint Tobiás, Henriett Pikó, Artúr Beke, Miklós Sipos, Péter Lakatos and János P. Kósa

Int. J. Mol. Sci. 2024, 25(23), 13227; https://doi.org/10.3390/ijms252313227 - 9 Dec 2024

Viewed by 3031

Abstract

The Human Microbiome Project (HMP), initiated in 2007, aimed to gather comprehensive knowledge to create a genetic and metabolic map of human-associated microorganisms and their contribution to physiological states and predisposition to certain diseases. Research has revealed that the human microbiome is highly diverse and exhibits significant interpersonal variability; consequently, its exact impact on health remains unclear. With the development of next-generation sequencing (NGS) technologies, the broad spectrum of microbial communities has been better characterized. The lower female genital tract, particularly the vagina, is colonized by various bacterial species, with Lactobacillus spp. predominating. The upper female genital tract, especially the uterus, was long considered sterile. However, recent studies have identified a distinct endometrial microbiome. A Lactobacillus-dominated microbiome of the female genital tract is associated with favorable reproductive outcomes, including higher success rates in natural conception and assisted reproductive technologies (ART). Conversely, microbial imbalances, or dysbiosis, marked by reduced Lactobacilli as well as an increased diversity and abundance of pathogenic species (e.g., Gardnerella vaginalis or Prevotella spp.), are linked to infertility, implantation failure, and pregnancy complications such as miscarriage and preterm birth. Dysbiosis can impair the vaginal or endometrial mucosal barrier and also trigger pro-inflammatory responses, disrupting essential reproductive processes like implantation. Despite growing evidence supporting the associations between the microbiome of the female genital tract and certain gynecological and obstetric conditions, clear microbial biomarkers have yet to be identified, and there is no consensus on the precise composition of a normal or healthy microbiome. The lack of standardized protocols and biomarkers limits the routine use of microbiome screening tests. Therefore, larger patient cohorts are needed to facilitate comparative studies and improve our understanding of the physiological microbiome profiles of the uterus and vagina, as well as how dysbiosis may influence clinical outcomes. Further research is required to refine diagnostic tools and develop personalized therapeutic strategies to improve fertility and pregnancy outcomes. Full article

(This article belongs to the Special Issue Molecular Mechanisms of Pregnancy Complications)

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17 pages, 1382 KiB

Open AccessReview

The Role of Catestatin in Preeclampsia

by Michalina Bralewska, Tadeusz Pietrucha and Agata Sakowicz

Int. J. Mol. Sci. 2024, 25(5), 2461; https://doi.org/10.3390/ijms25052461 - 20 Feb 2024

Cited by 4 | Viewed by 2085

Abstract

Preeclampsia (PE) is a unique pregnancy disorder affecting women across the world. It is characterized by the new onset of hypertension with coexisting end-organ damage. Although the disease has been known for centuries, its exact pathophysiology and, most importantly, its prevention remain elusive. The basis of its associated molecular changes has been attributed to the placenta and the hormones regulating its function. One such hormone is chromogranin A (CgA). In the placenta, CgA is cleaved to form a variety of biologically active peptides, including catestatin (CST), known inter alia for its vasodilatory effects. Recent studies indicate that the CST protein level is diminished both in patients with hypertension and those with PE. Therefore, the aim of the present paper is to review the most recent and most relevant in vitro, in vivo, and clinical studies to provide an overview of the proposed impact of CST on the molecular processes of PE and to consider the possibilities for future experiments in this area. Full article

(This article belongs to the Special Issue Molecular Mechanisms of Pregnancy Complications)

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