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Common Mechanisms in Gestational Diabetes, Preeclampsia, and Coronavirus Disease 2019

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: 31 January 2026 | Viewed by 2002

Special Issue Editor


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Guest Editor
International Research and Innovation in Medicine Program, Cedars–Sinai Medical Center, Los Angeles, CA 90048, USA
Interests: gestational diabetes; preeclampsia; inflammation; immunoglobulins; glycolisation; platelet aggregation; microvascular thrombosis; COVID-19

Special Issue Information

Dear Colleagues,

The leading cause of changes in the placenta is inflammation that is characterized by immunoglobulins, C-reactive protein, interleukins, and cytokines TNF-α and IFN-γ, as well as decidual cytokine IL-32.

We are pleased to invite you to present your results in the field of low-grade inflammation, immunoglobulins, glycolisation, platelet aggregation, and microvascular thrombosis. Inflammation induces tissue damage that can be measured with inflammation markers, immunoglobulins, glycolisation, platelet aggregation, and microvascular thrombosis.

The pro-angiogenic effects on the fetoplacental circulation support trophoblast growth, and placental angiogenesis will be monitored by measuring serum vascular endothelial growth factor (VEGF), Annexin A2, and placental growth factor (PGF). Also, it is required to investigate umbilical cord plasma sclerostin as a predictor of placental and newborn weight.

Suggested themes and article types for submissions: original research (brief reports, research letters), review articles (narrative, systematic, meta-analysis, clinical practice, epidemiology), case reports, and methodology articles. 

Research areas may include (but are not limited to) the following:

  • A high-risk pregnancy.
  • Hormonal and physiological changes that cause insulin resistance in GDM.
  • Gestational hypertension, preeclampsia, and eclampsia in coronavirus disease 2019.
  • Low-grade inflammation.
  • Glycolisation of immunoglobulins during GDM, PE, and COVID-19.
  • Placental angiogenesis.
  • Change in platelet aggregation during pregnancy.
  • Change in mother milk composition due to nutritional factors in GDM and PE.
We look forward to receiving your contributions.

Dr. Sandor G. Vari
Guest Editor

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Keywords

  • gestational diabetes
  • preeclampsia
  • inflammation
  • immunoglobulins
  • glycolisation
  • platelet aggregation
  • microvascular thrombosis
  • coronavirus disease 2019

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Published Papers (3 papers)

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Research

20 pages, 3845 KB  
Article
Vaping in Pregnancy: Unraveling Molecular Drivers of Preeclampsia and Fetal Growth Restriction
by Archarlie Chou, Olivia Hiatt, Benjamin Davidson, Paul R. Reynolds, Brett E. Pickett and Juan A. Arroyo
Int. J. Mol. Sci. 2025, 26(20), 10009; https://doi.org/10.3390/ijms262010009 - 15 Oct 2025
Abstract
Preeclampsia (PE) and intrauterine growth restriction (IUGR) are major pregnancy complications that are linked to placental dysfunction and environmental stimulation such as the use of electronic cigarettes (eCig). This study investigates the molecular impacts of timed eCig exposure in a C57BL/6 mouse model [...] Read more.
Preeclampsia (PE) and intrauterine growth restriction (IUGR) are major pregnancy complications that are linked to placental dysfunction and environmental stimulation such as the use of electronic cigarettes (eCig). This study investigates the molecular impacts of timed eCig exposure in a C57BL/6 mouse model of PE and IUGR using bulk RNA-sequencing of placental tissues. Pregnant mice were exposed to eCig vapor via nose-only system starting at embryonic day 12.5 (eCig-6d, before spiral artery (SA) invasion) or 14.5 (eCig-4d, after SA invasion) until E18.5 (necropsy), with healthy controls exposed to room air (n = 6/group). The eCig-4d group developed PE, whereas the eCig-6d group developed both PE and IUGR. RNA-seq analysis revealed 429 differentially expressed genes (DEGs) in eCig-4d (IUGR-like) group and 64 DEGs in eCig-6d (PE + IUGR-like) group compared to controls. Pathway and gene network analyses indicated that eCig-4d exposure activated NF-κB–driven inflammation, suppressed ECM organization and collagen biosynthesis, and downregulated vasoactive genes/mitochondrial-associated genes (NOS1/2), accompanied by impaired complement initiation and reduced both macrophage and monocyte signals. Similarly, eCig-6d exposure led to downregulation of complement-associated genes and granule-related components, possibly implicating weakened neutrophil responsiveness and compromised inflammatory resolution at the maternal–fetal interface. Our findings align with prior studies on physiological dysfunctions in PE and IUGR, while also providing novel insights into the temporally specific cellular responses induced by eCig exposure. Full article
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14 pages, 1466 KB  
Article
Placental Dysfunction Is Associated with Dysregulated Fibrinolytic System Activation
by Tetiana Yatsenko, Iryna Us, Daria Korolova, Svitlana Zhuk, Halyna Dziuba, Alona Nalbat, Svitlana Kharchenko, Sandor George Vari and Volodymyr Chernyshenko
Int. J. Mol. Sci. 2025, 26(19), 9339; https://doi.org/10.3390/ijms26199339 - 24 Sep 2025
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Abstract
During pregnancy, the maternal hemostatic system undergoes significant changes to support placental angiogenesis, maintain fetal blood flow, and ensure safe delivery. This study investigates the dysregulation of hemostasis in placental insufficiency and explores potential markers for diagnosing and managing this gestational complication. Thromboelastography, [...] Read more.
During pregnancy, the maternal hemostatic system undergoes significant changes to support placental angiogenesis, maintain fetal blood flow, and ensure safe delivery. This study investigates the dysregulation of hemostasis in placental insufficiency and explores potential markers for diagnosing and managing this gestational complication. Thromboelastography, coagulation and fibrinolysis functional assays, ELISA, and immunoblotting were employed to assess hemostasis dysregulation in placental dysfunction of two cohorts of pregnant women with placental dysfunction and healthy controls. Thromboelastographic analysis revealed no significant differences in clot lysis indices between the control and placental dysfunction groups, with values remaining within normal ranges, suggesting this method’s limitations for assessing fibrinolysis in pregnancy. The placental dysfunction group demonstrated moderately increased fibrinogen levels and platelet sensitivity to ADP, indicating hemostasis reactiveness. Significantly lower D-dimer levels, decreased plasminogen activator inhibitor activity (total PAI-1 + PAI-2), and increased plasminogen activator activity, driven primarily by uPA in the placental dysfunction group, indicated abnormal fibrinolysis. Immunoblotting confirmed elevated uPA/uPA-PAI complexes and reduced tPA/tPA-PAI complexes, indicating that shutdown of tPA-mediated fibrinolysis and induction of uPA-driven vessel-wall-associated proteolysis are linked to placental dysfunction. Placental dysfunction involves fibrinolytic system dysregulation, marked by decreased PAI and tPA, uPA overproduction, and hypofibrinolysis, contributing to thrombotic risks, impaired placental flow, and complications like fetal growth retardation. PAI/PA ratio and D-dimer levels have diagnostic potential for placental-dysfunction-associated complications. Full article
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17 pages, 5398 KB  
Article
Changes in Placentas of Pregnant Women Infected with COVID-19
by Solomiia Kramar, Zoia Nebesna, Yuliia Yakymchuk, Alla Boychuk, Oksana Shevchuk, Mykhaylo Korda and Sandor George Vari
Int. J. Mol. Sci. 2025, 26(17), 8596; https://doi.org/10.3390/ijms26178596 - 4 Sep 2025
Viewed by 886
Abstract
SARS-CoV-2 infection in pregnant women can lead to pregnancy-related complications. This work aims to study the spectrum of pathological changes in the placentas of SARS-CoV-2-infected pregnant women. The study involved 50 pregnant women with COVID-19 disease in the first (group I), second (group [...] Read more.
SARS-CoV-2 infection in pregnant women can lead to pregnancy-related complications. This work aims to study the spectrum of pathological changes in the placentas of SARS-CoV-2-infected pregnant women. The study involved 50 pregnant women with COVID-19 disease in the first (group I), second (group II), and third (group III) trimesters. Placental sections were examined by histopathology, electron microscopy, and immunohistochemistry to assess structural and molecular changes. The placentas of SARS-CoV-2-affected pregnant women exhibit nonspecific pathological changes, primarily associated with impaired blood circulation. The most frequent findings include thrombosis, chorangiosis, villous edema, and fibrinoid necrosis, all indicative of endothelial dysfunction. Increased expression of sclerostin and Annexin A2 was also detected in affected placentas. The main submicroscopic manifestations of placental insufficiency in COVID-19-affected women are dystrophic–destructive changes in the stroma of the villi, manifested by edema and fibrous processes, which cause significant disruption of the fetoplacental barrier. SARS-CoV-2 causes thrombotic and sclerotic changes, mainly in the maternal portion of the placenta. The manifestation of pathological changes in the placenta of COVID-19-affected women depends on the pregnancy period during which infection by SARS-CoV-2 has occurred. The established findings may provide insights into the connection between COVID-19 in pregnancy and antenatal and perinatal outcomes. Full article
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