Submit to IJMS Review for IJMS Propose a Special Issue

Journal Menu

Journal Browser

Molecular and Cellular Research in Pregnancy-Related Complications, 2nd Edition

Print Special Issue Flyer
Special Issue Editors
Special Issue Information
Keywords
Benefits of Publishing in a Special Issue
Published Papers

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 October 2025) | Viewed by 17432

Share This Special Issue

Special Issue Editor

Prof. Dr. Regina Komsa-Penkova

E-Mail Website
Guest Editor

Department of Biochemistry, Medical University-Pleven, 5800 Pleven, Bulgaria
Interests: extracellular matrix; pregnancy loss; thrombophilia; polymorphism; biomaterials; stem cells
Special Issues, Collections and Topics in MDPI journals

Special Issue Information

Dear Colleagues,

Reproductive complications, maternal and fetal morbidity, and mortality are common attributes of non-favorable pregnancies. The detection of at-risk pregnancies in early gestation is a challenging task for developing corrective and curative strategies.

Biomarkers in maternal circulation have been explored to evaluate risk in early pregnancy, but thus far, they are only reliable for the diagnostics of rather limited pregnancy complications.

Recent studies highlight the role of systemic and placental oxidative stress as an essential factor in the etiology of early pregnancy losses. Trophoblast invasion under low-oxygen conditions and hypoxia-induced oxidative stress are important regulators of the physiological development of the placenta and embryo in early pregnancy. Nonetheless, when oxidative stress exceeds the normal physiological level in the maternal–fetal environment, orchestrated by blood cell damage, accelerated senescence and early eryptosis, complications such as miscarriage, pre-eclampsia and limited intrauterine development may occur.

The imbalance of immune tolerance at the maternal–fetal interface is another important factor in the occurrence of pregnancy loss. The immunologic events at the maternal–fetal interface in early pregnancy are complex, involving numerous immune cells and molecules.

A promising approach for investigation of the placenta and placental–fetus interaction comes from the fact that trophoblast cells could migrate from the placenta into the reproductive tract, and could then be collected and separated from maternal cells for the analysis of fetal proteins, DNA, RNA and other informative molecules.

This Special Issue aims at expanding the current knowledge on the structural and behavioral imbalance of peripheral and endometrial immune cells, red blood cells, trophoblasts, decidual cells and stem cells in pregnancy-related complications. Experimental studies and reviews are welcome for submission.

More published papers can be found in the closed Special Issue “Molecular and Cellular Research in Pregnancy-Related Complications”.

Prof. Dr. Regina Komsa-Penkova
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 250 words) can be sent to the Editorial Office for assessment.

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 loss/miscarriage
pregnancy complications
pre-eclampsia
maternal–placental–fetal interactions
trophoblast
immune cells
immune tolerance
red blood cells
oxidative stress
blood and fetal proteins
DNA
RNA
stem cells

Benefits of Publishing in a Special Issue

Ease of navigation: Grouping papers by topic helps scholars navigate broad scope journals more efficiently.
Greater discoverability: Special Issues support the reach and impact of scientific research. Articles in Special Issues are more discoverable and cited more frequently.
Expansion of research network: Special Issues facilitate connections among authors, fostering scientific collaborations.
External promotion: Articles in Special Issues are often promoted through the journal's social media, increasing their visibility.
Reprint: MDPI Books provides the opportunity to republish successful Special Issues in book format, both online and in print.

Further information on MDPI's Special Issue policies can be found here.

Published Papers (6 papers)

Download All Papers

Order results

Result details

Show export options Show export options

Select all

Export citation of selected articles as:

Research

Jump to: Review

19 pages, 3859 KB

Open AccessArticle

Maternal Gestational Diabetes Impairs Fetoplacental Insulin-Induced Vasodilation via AKT/eNOS Pathway and Reduces Placental Efficiency

by Clara M. Hengst, Maria de Leyre Villar-Ballesteros, Heike Brendel, Sindy Giebe, Coy Brunssen, Alexander Frühauf, Cahit Birdir, Paul D. Taylor, Lucilla Poston and Henning Morawietz

Int. J. Mol. Sci. 2025, 26(23), 11507; https://doi.org/10.3390/ijms262311507 - 27 Nov 2025

Viewed by 273

Abstract

Gestational Diabetes Mellitus (GDM) increases the long-term risk for metabolic and cardiovascular diseases in the offspring. However, the underlying mechanisms are not well understood. This study investigates the impact of GDM on fetoplacental vascular function and molecular mechanisms underlying endothelial dysfunction. Clinical data and tissue samples were collected from normoglycemic (NG, n = 33) and GDM (n = 19) pregnancies. Offspring in the GDM group were delivered earlier, had a larger placental size, and had a reduced placental efficiency. Functional analysis using a Mulvany myograph demonstrated a significant impairment of insulin-mediated vasodilation in fetoplacental vessels of GDM patients compared to NG controls. This vascular dysfunction was associated with a reduction in total insulin receptor protein expression. Further investigation revealed an impaired PI3K/AKT/eNOS signaling pathway, as endothelial cells from GDM pregnancies showed a deficient insulin-induced phosphorylation of AKT. These results indicate that maternal GDM induces insulin resistance and endothelial dysfunction in the fetoplacental vasculature through impairment of the AKT/eNOS pathway, providing a key mechanism for its adverse neonatal outcomes and the increased lifelong cardiovascular risk in the offspring. Full article

(This article belongs to the Special Issue Molecular and Cellular Research in Pregnancy-Related Complications, 2nd Edition)

► Show Figures

Figure 1

15 pages, 4108 KB

Open AccessArticle

Placenta-Derived Secretions Promote Liver Dysfunction, and Hepatic Serum Amyloid A Mediates Kidney Inflammatory Response in a Preeclampsia-like Mouse Model

by Ren Ozawa, Sae Suzuki, Ayaka Shirota, Shota Nomura, Takanori Komada, Masafumi Takahashi, Hisataka Iwata and Koumei Shirasuna

Int. J. Mol. Sci. 2025, 26(21), 10737; https://doi.org/10.3390/ijms262110737 - 4 Nov 2025

Viewed by 595

Abstract

Preeclampsia (PE) is characterized by maternal hypertension accompanied with multi-organ dysfunction, such as maternal hepatic and renal dysfunction. Abnormal placental conditions may play a key role in regulating maternal organ function by promoting systemic inflammation. This study aimed to test the hypothesis that placenta-derived secretions contribute to hepatic and renal injury through interorgan communication using a PE-like mouse model. Pregnant mice were infused with angiotensin II (Ang II) from gestational day (GD) 12 (GD1 defined as the day of plug detection). Ang II infusion induced maternal hypertension, as well as liver injury (elevated serum amyloid A [SAA] secretion and alanine aminotransferase levels) and kidney injury (tubular damage with KIM-1 protein expression and immune cell infiltration). Treatment with placental-conditioned medium (CM) from Ang II-infused mice, but not from the control mice, stimulated SAA expression in liver cells. On the other hand, the effects of placental-CM from both the control and Ang II groups on kidney tubular cells were comparable. These findings suggest that placenta-derived secretions in the Ang II-induced PE-like phenotype specifically promote excessive SAA production in the liver. Furthermore, SAA administration in pregnant mice did not cause tubular injury but did promote renal immune cell infiltration, indicating that elevated hepatic SAA levels may contribute to maternal kidney inflammation. Taken together, these results suggest the presence of an in vivo organ network involving the placenta, liver, and kidneys during pregnancy, where dysfunction in one organ may exacerbate the pathogenesis of PE. Full article

(This article belongs to the Special Issue Molecular and Cellular Research in Pregnancy-Related Complications, 2nd Edition)

► Show Figures

Figure 1

10 pages, 377 KB

Open AccessArticle

Functional MPO Polymorphisms and Haplotypes Affect Both Myeloperoxidase Levels and Association with Hypertensive Disorders of Pregnancy

by Daniela Alves Pereira, Marcelo Rizzatti Luizon, Ricardo Carvalho Cavalli, Jose Eduardo Tanus-Santos and Valéria Cristina Sandrim

Int. J. Mol. Sci. 2025, 26(15), 7071; https://doi.org/10.3390/ijms26157071 - 23 Jul 2025

Viewed by 948

Abstract

Preeclampsia (PE) shares common pathophysiological mechanisms with cardiovascular diseases, including endothelial dysfunction and exacerbated inflammatory response. Myeloperoxidase (MPO) has been suggested as a biomarker for cardiovascular risk, and its circulating levels are contradictory in PE. Elevated levels of MPO can promote host tissue damage and trigger vascular injury. MPO gene polymorphisms affect circulating MPO levels under different conditions. To date, no studies have investigated whether MPO polymorphisms influence MPO levels in hypertensive disorders of pregnancy. In this study, we examined the impact of two specific MPO polymorphisms—rs2243828 and rs2071409—and their associated haplotypes on MPO levels. We also explored their potential association with gestational hypertension (GH) and preeclampsia (PE). Our study included 136 healthy pregnant women (HP), including 118 with GH and 140 with PE. Genotyping was performed using TaqMan allele discrimination assays, and MPO levels were quantified using an ELISA assay. The TT genotype of the rs2243828 polymorphism was associated with lower MPO concentration in GH, and the CC genotype presented a higher frequency in the GH group than the HP group. The AC+CC rs2071409 polymorphism was associated with lower MPO concentration in GH. We also found that the ‘C, C’ haplotype was less frequent and was associated with lower MPO concentration in PE. Our findings suggest that both rs2243828 and rs2071409 polymorphisms might contribute to MPO levels in GH and that the haplotype ‘C, C’ formed by them may protect against PE. Full article

(This article belongs to the Special Issue Molecular and Cellular Research in Pregnancy-Related Complications, 2nd Edition)

► Show Figures

Figure 1

17 pages, 3334 KB

Open AccessArticle

Alterations in P-glycoprotein Expression in the Placenta of Obese Rats and Humans

by Péter Szatmári, Kata Kira Kemény, Andrea Surányi, Yakov Rachamim and Eszter Ducza

Int. J. Mol. Sci. 2025, 26(14), 6976; https://doi.org/10.3390/ijms26146976 - 20 Jul 2025

Cited by 1 | Viewed by 1132

Abstract

Obesity affects approximately 30% of pregnancies worldwide and is one of the leading metabolic disorders among pregnant women. Maternal obesity is often associated with placental dysfunction and structural alterations, which increase the risk of developing complications. Efflux transporters, including P-glycoprotein (P-gp), may impact placental function and fetal development. Consequently, our research examined the effects of obesity on P-glycoprotein expression in both a rat model and human placental tissue. P-gp expression was measured by RT-PCR and Western blot techniques in human and rat placental tissues. Moreover, we further characterized the high-fat and high-sugar diet (HFHSD)-induced gestational obesity rat model by measuring tissue weights. Significant decreases were observed in fetal, placental, and uterus weights in the obese animals near the end of pregnancy. In obese rats, mRNA and protein expression of placental P-gp showed a reduction on gestation days 15, 20, and 22. A similar P-gp reduction was observed in the term placenta in obese women in mRNA and protein levels. We hypothesize that the reduced expression of P-gp may heighten the susceptibility of both the fetus and placenta to P-gp substrates. This alteration could potentially result in an increased risk of pregnancy complications and obesity-related drug contraindications linked to P-gp transport during pregnancy. Full article

(This article belongs to the Special Issue Molecular and Cellular Research in Pregnancy-Related Complications, 2nd Edition)

► Show Figures

Figure 1

Review

Jump to: Research

22 pages, 2611 KB

Open AccessReview

Exploring Potential Biomarkers in Recurrent Pregnancy Loss: A Literature Review of Omics Studies to Molecular Mechanisms

by Lan Li and Kwang-Hyun Baek

Int. J. Mol. Sci. 2025, 26(5), 2263; https://doi.org/10.3390/ijms26052263 - 4 Mar 2025

Cited by 7 | Viewed by 4938

Abstract

Recurrent pregnancy loss (RPL) is characterized by the occurrence of three or more consecutive spontaneous pregnancy losses before 20–24 weeks of gestation. Despite significant progress in the investigation of the biological pathways associated with unexplained RPL, the precise molecular mechanisms remain elusive. Recent advances in multi-omics approaches have identified numerous biomarkers that offer potential avenues for understanding the underlying complexities of RPL. The aim of this comprehensive literature review was to investigate the functional roles of these candidate markers and explore the possible key mechanisms that may contribute to RPL. We also aimed to elucidate the functional networks predicted by omics analyses, which hold promise for providing invaluable insights into novel diagnostic and therapeutic strategies for women experiencing RPL. Furthermore, this review expands on clinical implications and possible applications, highlighting those currently moving towards clinical use and ongoing studies developing in this direction. Full article

(This article belongs to the Special Issue Molecular and Cellular Research in Pregnancy-Related Complications, 2nd Edition)

► Show Figures

Figure 1

35 pages, 3354 KB

Open AccessReview

Oxidative Stress and Placental Pathogenesis: A Contemporary Overview of Potential Biomarkers and Emerging Therapeutics

by Ioana Vornic, Victor Buciu, Cristian George Furau, Pusa Nela Gaje, Raluca Amalia Ceausu, Cristina-Stefania Dumitru, Alina Cristina Barb, Dorin Novacescu, Alin Adrian Cumpanas, Silviu Constantin Latcu, Talida Georgiana Cut and Flavia Zara

Int. J. Mol. Sci. 2024, 25(22), 12195; https://doi.org/10.3390/ijms252212195 - 13 Nov 2024

Cited by 33 | Viewed by 8604

Abstract

Oxidative stress (OS) plays a crucial role in placental pathogenesis and pregnancy-related complications. This review explores OS’s impact on placental development and function, focusing on novel biomarkers for the early detection of at-risk pregnancies and emerging therapeutic strategies. We analyzed recent research on OS in placental pathophysiology, examining its sources, mechanisms, and effects. While trophoblast invasion under low-oxygen conditions and hypoxia-induced OS regulate physiological placental development, excessive OS can lead to complications like miscarriage, preeclampsia, and intrauterine growth restriction. Promising OS biomarkers, including malondialdehyde, 8-isoprostane, and the sFlt-1/PlGF ratio, show potential for the early detection of pregnancy complications. Therapeutic strategies targeting OS, such as mitochondria-targeted antioxidants, Nrf2 activators, and gasotransmitter therapies, demonstrate encouraging preclinical results. However, clinical translation remains challenging. Future research should focus on validating these biomarkers in large-scale studies and developing personalized therapies to modulate placental OS. Emerging approaches like extracellular vesicle-based therapies and nanomedicine warrant further investigation for both diagnostic and therapeutic applications in pregnancy-related complications. Integrating OS biomarkers with other molecular and cellular markers offers improved potential for the early identification of at-risk pregnancies. Full article

(This article belongs to the Special Issue Molecular and Cellular Research in Pregnancy-Related Complications, 2nd Edition)

► Show Figures

Journal Menu

Journal Browser

Molecular and Cellular Research in Pregnancy-Related Complications, 2nd Edition

Share This Special Issue

Special Issue Editor

Special Issue Information

Keywords

Benefits of Publishing in a Special Issue

Published Papers (6 papers)

Research

Review

Further Information

Guidelines

MDPI Initiatives

Follow MDPI