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New Insights in the Mechanism of Obstetrical Complications: Prevention, Diagnosis, Monitoring, Treatment

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: 20 July 2026 | Viewed by 9522

Special Issue Editors

Prof. Dr. Lucia Maria Procopciuc

E-Mail Website
Guest Editor
Medical Biochemistry Department, “Iuliu Hațieganu” University of Medicine and Pharmacy, Cluj-Napoca, Romania
Interests: genetics; epigenetics; medical biochemistry; metabolic disorders
Special Issues, Collections and Topics in MDPI journals
Prof. Dr. Roxana Liana Lucaciu

E-Mail Website
Guest Editor
Pharmaceutical Biochemistry and Clinical Laboratory Department, “Iuliu Hațieganu” University of Medicine and Pharmacy, Cluj-Napoca, Romania
Interests: (clinical) biochemistry; medicinal chemistry; drug discovery; anticancer
Special Issues, Collections and Topics in MDPI journals

Special Issue Information

Dear Colleagues,

Some women experience health problems during pregnancy. These complications can involve the mother's health, the fetus's health, or both. Even women who were healthy before becoming pregnant can experience complications. These complications may make the pregnancy a high-risk pregnancy.

Obtaining early and regular prenatal care can help decrease the risk for problems by enabling health care providers to diagnose, treat, or manage conditions before they become serious. Prenatal care can also help identify mental health concerns related to pregnancy, such as anxiety and depression.

Some common complications of pregnancy include, but are not limited to, the following: high blood pressure, gestational diabetes, infections, preeclampsia, preterm labor, depression, anxiety, pregnancy loss/miscarriage, stillbirth, premature membrane rupture, vaginal bleeding, placenta previa, and anemia.

In this Special Issue, we will include original articles, reviews, and case reports regarding biochemical, genetic, and epigenetic determinations with a role in the prevention, diagnosis, monitoring, and treatment of these obstetrical complications. Manuscripts may consider addressing maternal, fetal, or both risk factors in modulating the increased risk of morbidity and mortality.

Furthermore, this issue will take into account in silico, experimental in vitro and in vivo studies and clinical studies with a higher potential to improve the management (prevention, diagnosis, treatment) of obstetrical complications.

Prof. Dr. Lucia Maria Procopciuc
Prof. Dr. Roxana Liana Lucaciu
Guest Editors

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

  • high blood pressure
  • gestational diabetes
  • infections
  • preeclampsia
  • eclampsia
  • preterm labor
  • depresion
  • anxiety
  • pregnancy loss/miscarriage
  • stillbirth
  • premature membrane rupture
  • vaginal bleeding
  • placenta previa
  • anemia
  • intrauterine growth restriction
  • maternal risk factors
  • fetal risk factors
  • endothelial dysfunction
  • angiogenesis
  • oxidative stress
  • hormonal modifications
  • dyslipidemia
  • biochemical
  • genetic
  • epigenetic determinations
  • computational analysis

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Published Papers (6 papers)

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Research

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24 pages, 8616 KB  
Article
Integrated Clinical and Molecular Profiling of Fetal Growth Disorders in the First Trimester
by Natalia Starodubtseva, Alisa Tokareva, Natalia Frankevich, Alexey Kononikhin, Anna Bugrova, Maria Indeykina, Evgenii Kukaev, Anna Derenko, Vladimir Frankevich, Evgeny Nikolaev and Gennady Sukhikh
Int. J. Mol. Sci. 2026, 27(10), 4192; https://doi.org/10.3390/ijms27104192 - 8 May 2026
Viewed by 251
Abstract
This prospective study evaluated first-trimester markers in pregnancies with isolated and combined forms of fetal growth disorders and gestational diabetes mellitus (GDM). Among 1869 screened women, the analysis included 83 controls, 55 GDM, 22 isolated intrauterine growth restriction (iIUGR), and 33 isolated large-for-gestational-age [...] Read more.
This prospective study evaluated first-trimester markers in pregnancies with isolated and combined forms of fetal growth disorders and gestational diabetes mellitus (GDM). Among 1869 screened women, the analysis included 83 controls, 55 GDM, 22 isolated intrauterine growth restriction (iIUGR), and 33 isolated large-for-gestational-age (iLGA) cases, with GDM subgroups stratified by fetal growth (GDM with normal fetal weight, GDM + IUGR, and GDM + LGA). First-trimester clinical and routine biochemical parameters were recorded, and serum concentrations of 80 proteins were measured using targeted LC-MRM-MS proteomics. Different trajectories emerged: IUGR phenotypes showed low PAPP-A/PlGF and high TSH (p < 0.01), indicating early placental insufficiency, while macrosomia showed opposite trends. GDM + IUGR represented the most severe “double hit” phenotype (lowest PlGF, earliest delivery), whereas GDM + LGA showed increased umbilical artery resistance despite excessive growth, suggesting endothelial dysfunction. Targeted proteomics revealed characteristic signatures: iIUGR featured low complement (C4A|C4B) and IGF proteins (IGFALS, IGFBP3) versus GDM and iLGA (p < 0.001); GDM + IUGR showed elevated PZP and CD5L versus iIUGR (p < 0.05); GDM + LGA was marked by high C4BPA and low RBP4, SERPINA7 versus iLGA (p < 0.05). Complement and IGF pathways were consistently implicated. Machine learning achieved 77% sensitivity for IUGR prediction using clinical parameters and 88% sensitivity for LGA prediction using proteomic data. These findings demonstrate that fetal growth disorders represent pathophysiologically unique entities detectable in the first trimester, enabling early risk stratification and personalized management. Full article
(This article belongs to the Special Issue New Insights in the Mechanism of Obstetrical Complications: Prevention, Diagnosis, Monitoring, Treatment)
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16 pages, 2256 KB  
Article
PCYT1B-Targeting miRNAs as Potential Biomarkers for Placental Diseases
by Ha Eun Shin, Jin Seok, Jae Yeon Kim, Dong-Hyun Cha, Joong Sik Shin and Gi Jin Kim
Int. J. Mol. Sci. 2026, 27(9), 4039; https://doi.org/10.3390/ijms27094039 - 30 Apr 2026
Viewed by 255
Abstract
Obstetrical diseases are complications associated with pregnancy or childbirth that can cause maternal sequelae and fetal complications. Among them, preeclampsia (PE) and preterm labor (PTL) are major causes of premature birth and are associated with an increased risk of cerebral palsy, developmental delay, [...] Read more.
Obstetrical diseases are complications associated with pregnancy or childbirth that can cause maternal sequelae and fetal complications. Among them, preeclampsia (PE) and preterm labor (PTL) are major causes of premature birth and are associated with an increased risk of cerebral palsy, developmental delay, and hearing impairment in infants. However, reliable diagnostic markers and therapeutic strategies for obstetrical diseases remain limited. The aim of this study was to investigate genes associated with obstetrical diseases and to evaluate the correlation between phosphocholine cytidylyltransferase 1 beta (PCYT1B) and miRNAs targeting PCYT1B for diagnostic analysis in PE and PTL. Using miRNA array analysis and luciferase assays, we identified PCYT1B, a key enzyme involved in phosphocholine metabolism in reproductive tissues, together with several candidate miRNAs targeting PCYT1B, including miR-3065-3p, miR-4660, miR-6752-5p, miR-6842-5p and miR-7110-5p. qRT-PCR analysis revealed a significant correlation between PCYT1B and these miRNAs in placental tissues from patients with PE and PTL (p < 0.05). Immunofluorescence staining further demonstrated that PCYT1B was localized in the syncytiotrophoblast layer of placental tissues, and its protein expression was consistent with mRNA expression levels. To investigate the functional role of these miRNAs, trophoblast cells were treated with miRNA mimics and inhibitors. These treatments significantly altered trophoblast invasion capacity and regulated the expression of migration-related genes, including RhoA, Rac1 and ROCK. Collectively, our findings suggest that miRNAs targeting PCYT1B may regulate trophoblast function and may play a key role in placental development and obstetrical diseases. These results indicate that PCYT1B and its regulatory miRNAs could serve as potential biomarkers for PE and PTL and may provide insights into the development of miRNA-based diagnostic strategies. Full article
(This article belongs to the Special Issue New Insights in the Mechanism of Obstetrical Complications: Prevention, Diagnosis, Monitoring, Treatment)
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12 pages, 1039 KB  
Article
Investigation of Novel Predictive Biomarkers for Preeclampsia in Second-Trimester Amniotic Fluid
by Hyo Eun Lee, Yeonseong Jeong, Jue Young Kim, Ha-Yeon Shin, Young-Han Kim and Min-A Kim
Int. J. Mol. Sci. 2025, 26(21), 10530; https://doi.org/10.3390/ijms262110530 - 29 Oct 2025
Viewed by 1192
Abstract
Preeclampsia (PE) is a major cause of maternal and perinatal morbidity, and early prediction is critical for timely intervention. This study aimed to identify predictive biomarkers for PE through transcriptomic analysis of second-trimester amniotic fluid supernatant (AFS) collected prior to clinical symptom onset. [...] Read more.
Preeclampsia (PE) is a major cause of maternal and perinatal morbidity, and early prediction is critical for timely intervention. This study aimed to identify predictive biomarkers for PE through transcriptomic analysis of second-trimester amniotic fluid supernatant (AFS) collected prior to clinical symptom onset. AFS samples from women who later developed PE (n = 7) and matched controls (n = 7) underwent RNA sequencing to identify differentially expressed genes (DEGs). Candidate genes were validated by real-time PCR in HTR-8/SVneo cells exposed to fluid shear stress at 3, 10, and 20 dyn/cm2 for 24 h, mimicking the hemodynamic environment of PE, and siRNA-mediated knockdown was used to assess effects on trophoblast migration and invasion. RNA sequencing revealed 19 DEGs, with 3 upregulated and 16 downregulated genes in the PE group. HOOK2 emerged as the most significantly upregulated gene. Four candidate genes, including HOOK2, CCDC160, CKB, and PARP15, were selected for further validation. HOOK2 mRNA expression significantly increased with higher shear stress levels, consistent with sequencing data. Knockdown of HOOK2 led to a significant increase in trophoblast invasion, while migration showed no significant change. These findings suggest that HOOK2 may serve as a promising early biomarker for PE by modulating trophoblast invasiveness under altered hemodynamic conditions, with potential to improve risk stratification and personalized monitoring in pregnancy. Full article
(This article belongs to the Special Issue New Insights in the Mechanism of Obstetrical Complications: Prevention, Diagnosis, Monitoring, Treatment)
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8 pages, 520 KB  
Communication
Relative Expression of Peptidylarginine Deiminase 2 and Sex Steroid Receptors in XX and XY Mouse Placenta
by Amanda Wewer, Autumn Bennitt, Emily Hinners, Morgan Helmich, Nathan Schnepp, Sean Pitcher, Agata M. Parsons and Gerrit J. Bouma
Int. J. Mol. Sci. 2025, 26(21), 10523; https://doi.org/10.3390/ijms262110523 - 29 Oct 2025
Viewed by 1456
Abstract
Although female (XX) and male (XY) placentas generally function the same, it is evident that there are sex-specific postnatal health outcomes following placental dysfunction and pregnancy complications. Although the underlying causes for these sex differences are unclear, it is postulated that differences in [...] Read more.
Although female (XX) and male (XY) placentas generally function the same, it is evident that there are sex-specific postnatal health outcomes following placental dysfunction and pregnancy complications. Although the underlying causes for these sex differences are unclear, it is postulated that differences in XX and XY placental function are involved due to sex chromosomes and/or sex steroids. Studies in breast and prostate cancer cells demonstrated a role for the citrullination enzyme peptidylarginine deiminase 2 (PAD2) in post-translational regulation of estrogen (ESR) and androgen receptor (AR) signaling. The goal of this study is to determine if PAD2 is present in mouse placentas and if XX versus XY differences exist in the relative level of PAD2. Fetuses and placentas were collected from three pregnant mice (C57BL6) at 14 days of gestation. Total RNA and protein were isolated from XX and XY placentas, and relative mRNA and protein were analyzed by real-time PCR and Western blot. AR and PAD2 levels were significantly higher in XY than in XX placentas. This study is the first to demonstrate XX and XY differences in PAD2 and AR in the placenta. It suggests a role for PAD2 regulation of androgen receptor signaling in the XY placenta. Full article
(This article belongs to the Special Issue New Insights in the Mechanism of Obstetrical Complications: Prevention, Diagnosis, Monitoring, Treatment)
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Review

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33 pages, 6777 KB  
Review
Understanding Preeclampsia: Integrating Placental Dysfunction, Immune Dysregulation and microRNA-Mediated Epigenetic Regulation
by Lucia Maria Procopciuc, Gabriela Valentina Caracostea, Adriana Corina Hangan and Roxana Liana Lucaciu
Int. J. Mol. Sci. 2026, 27(10), 4281; https://doi.org/10.3390/ijms27104281 - 11 May 2026
Viewed by 309
Abstract
Preeclampsia is a pregnancy-specific multisystem disorder and a major cause of maternal and perinatal morbidity and mortality worldwide. This narrative review summarizes current evidence on the principal risk factors and pathophysiological mechanisms involved in its development. The disease is best explained by the [...] Read more.
Preeclampsia is a pregnancy-specific multisystem disorder and a major cause of maternal and perinatal morbidity and mortality worldwide. This narrative review summarizes current evidence on the principal risk factors and pathophysiological mechanisms involved in its development. The disease is best explained by the two-stage model: in stage 1, inadequate trophoblast invasion and incomplete spiral artery remodeling lead to placental hypoperfusion, hypoxia, and oxidative stress; in stage 2, the hypoxic placenta releases anti-angiogenic and pro-inflammatory factors, including soluble fms-like tyrosine kinase-1 (sFlt-1) and soluble endoglin (sEng), which trigger systemic endothelial dysfunction and the maternal clinical syndrome. The review highlights the central role of angiogenic imbalance, immune dysregulation, and chronic inflammation in disease progression. Particular emphasis is placed on maternal risk factors such as primiparity, advanced maternal age, obesity, diabetes mellitus, chronic hypertension, multiple pregnancy, prior preeclampsia, genetic susceptibility, and epigenetic regulation. We also emphasize the contribution of microRNAs in relation to placental hypoxia, trophoblast invasion, angiogenesis, endothelial injury and microchimerism to the development of preeclampsia. The review also examines the role of T helper 1 (Th1)/Th2/Th17/regulatory T cells (Treg) imbalance and uterine natural killer cell dysfunction at the maternal–fetal interface. Improved understanding of these interconnected mechanisms may support earlier diagnosis, better risk stratification, and the development of targeted preventive and therapeutic strategies. Full article
(This article belongs to the Special Issue New Insights in the Mechanism of Obstetrical Complications: Prevention, Diagnosis, Monitoring, Treatment)
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22 pages, 1279 KB  
Review
From Molecular Insights to Clinical Management of Gestational Diabetes Mellitus—A Narrative Review
by Mohamed-Zakaria Assani, Lidia Boldeanu, Maria-Magdalena Manolea, Mihail Virgil Boldeanu, Isabela Siloși, Alexandru-Dan Assani, Constantin-Cristian Văduva and Anda Lorena Dijmărescu
Int. J. Mol. Sci. 2025, 26(17), 8719; https://doi.org/10.3390/ijms26178719 - 7 Sep 2025
Cited by 5 | Viewed by 5132
Abstract
Gestational diabetes mellitus (GDM) is one of the most common metabolic complications during pregnancy, affecting up to 14% of pregnancies globally. GDM is characterized by glucose intolerance that arises or is first identified during pregnancy and is linked to significant short- and long-term [...] Read more.
Gestational diabetes mellitus (GDM) is one of the most common metabolic complications during pregnancy, affecting up to 14% of pregnancies globally. GDM is characterized by glucose intolerance that arises or is first identified during pregnancy and is linked to significant short- and long-term adverse outcomes for both mothers and their offspring. The pathophysiology of GDM involves more than maternal insulin resistance and β-cell dysfunction. It is influenced by complex interactions among placental hormones, adipokines, inflammatory mediators, and oxidative stress pathways. Additionally, placental-derived exosomes and metabolomic signatures have emerged as promising biomarkers for early prediction and monitoring of the disease. Despite advancements in clinical diagnosis and management, including lifestyle interventions and pharmacological treatments, current strategies are still inadequate to prevent complications for both mothers and newborns entirely. Recent molecular insights into GDM development have been explored, along with emerging biomarkers and potential therapies. This synthesis also considers prospects for precision medicine strategies that could significantly improve GDM management. The urgent need for improved prevention and treatment of GDM is evident. A deeper understanding of the molecular foundations of GDM is essential and urgent, as it may enhance clinical outcomes and provide opportunities for early prevention of intergenerational metabolic disease risk. Full article
(This article belongs to the Special Issue New Insights in the Mechanism of Obstetrical Complications: Prevention, Diagnosis, Monitoring, Treatment)
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