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Molecular Advances in Obstetrical and Gynaecological Disorders

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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: 20 June 2025 | Viewed by 7894

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Dr. Panagiotis Christopoulos

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2nd Department of Obstetrics and Gynecology, Medical School, National and Kapodistrian University of Athens, Athens, Greece
Interests: gynecology; obstetrics; reproductive; endocrinology; mullerian anomalies; PCOS; pediatric gynecology; high-risk pregnancy; adolescent gynecology; minimally invasive surgery
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Special Issue Information

Dear Colleagues,

Gynaecological disorders, ranging from developmental disorders to cancer, represent some of the most common health conditions in women that affect their health-related quality of life and life expectancy, both in reproductive age and after menopause. With regard to pregnancy, several disorders, such as diabetes and hypertension, frequently affect both the pregnant woman's and the offspring’s health, giving rise to negative intergenerational cycles.

Recent advances in molecular biology have shed light on the aetiology and pathophysiology of obstetrical and gynaecological complaints, which facilitated research in diagnosing and managing these disorders. For example, molecular research has indicated several biomarkers for the early diagnosis of cervical cancer, and micro-RNAs have been involved in the non-invasive diagnosis of endometriosis. In addition, recent research in genetics and epigenetics has enlightened causative pathways in developmental disorders, such as Mayer–Rokitansky–Küster–Hauser (MRKH) Syndrome. Furthermore, molecular techniques are applied in precision-medicine research regarding infertility and ovarian disorders, such as polycystic ovary syndrome (PCOS), anovulation, and premature ovarian failure.

This Special Issue on “Molecular Advances in Obstetrical and Gynaecological Disorders” aims to include clinical and basic science in the form of both original research and review papers, investigating obstetrical and gynaecological disorders with respect to molecular pathology, diagnostics, and therapeutics; molecular biology, oncology, and immunology; molecular genetics and genomics; molecular endocrinology and metabolism; and molecular informatics.

Dr. Panagiotis Christopoulos
Guest Editor

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Keywords

female reproduction
infertility
embryo development
genealogical disorders
cancer
biomarkers
molecular therapy
epigenetics

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Published Papers (6 papers)

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Research

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30 pages, 4251 KiB

Open AccessArticle

Asymmetric Dimethylaminohydrolase Gene Polymorphisms Associated with Preeclampsia Comorbid with HIV Infection in Pregnant Women of African Ancestry

by Mbuso Herald Mthembu, Samukelisiwe Sibiya, Zinhle Pretty Mlambo, Nompumelelo P. Mkhwanazi and Thajasvarie Naicker

Int. J. Mol. Sci. 2025, 26(7), 3271; https://doi.org/10.3390/ijms26073271 - 1 Apr 2025

Viewed by 353

Abstract

Asymmetric dimethylarginine (ADMA) is an endogenous nitric oxide synthase (NOS) inhibitor associated with vascular disease, which is prevalent in human plasma. Two isoforms of the enzyme dimethylarginine dimethylaminohydrolase (DDAH), DDAH 1 and 2, degrade ADMA. This study investigates the association of DDAH 1 (rs669173, rs7521189) and DDAH 2 gene polymorphisms (rs805305, rs3131383) with the risk of preeclampsia (PE) comorbidity with human immunodeficiency virus (HIV) infection in pregnant women of African ancestry. A total of 405 women were enrolled in this study: 204 were PE, 201 were normotensive pregnant, and 202 were HIV positive. DNA was extracted from whole blood, and SNPs (rs669173, rs7521189, rs805305, and rs3131383) were amplified to detect single-nucleotide polymorphisms (SNPs). After PCR amplification, allelic discrimination was examined. Comparisons were conducted utilizing the Chi-squared test. Our findings indicated that preeclamptic women displayed a greater prevalence of the three variants compared to those with both PE and HIV infection. There is an association between the rs669173 and rs7521189 SNPs of the DDAH 1 gene and rs3131383 of the DDAH 2 gene, which could play a role in reducing the bioavailability of nitric oxide (NO), which affects endothelial function, leading to the development of PE in pregnant women of African ancestry. In contrast, the rs805305 variant of the DDAH 2 gene was not significantly associated with PE development. Interestingly, none of the SNPs investigated correlated with HIV infection or could be attributed to the human allelic variant influence on HIV infection outcome. Full article

(This article belongs to the Special Issue Molecular Advances in Obstetrical and Gynaecological Disorders)

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7 pages, 531 KiB

Open AccessCommunication

Association of the miR-143 Gene rs353292 Polymorphism with Recurrent Pregnancy Loss in Caucasian Women: A Novel Finding in a Multifactorial Devastating Problem

by Sofoklis Stavros, Anastasios Potiris, Panagiotis Christopoulos, Natalia Zacharopoulou, Vasiliki Kyrli, Despoina Mavrogianni, Athanasios Zikopoulos, Eirini Drakaki, Theodoros Karampitsakos, Spyridon Topis, Nikolaos Machairiotis, Angeliki Gerede, Chara Skentou, Peter Drakakis and Ekaterini Domali

Int. J. Mol. Sci. 2024, 25(22), 11952; https://doi.org/10.3390/ijms252211952 - 7 Nov 2024

Viewed by 833

Abstract

The purpose of this prospective case–control study is to investigate the correlation of the miR-143 gene rs353292 polymorphism in Caucasian women with recurrent pregnancy loss (RPL) compared to a matched control group with at least one live birth and without pregnancy losses. In total, 110 women with recurrent pregnancy losses and 95 control women were recruited. Peripheral blood was collected from all women, and the isolation of DNA was performed with Monarch Genomic DNA Purification. Polymerase chain reaction was applied to amplify the DNA sequence of the miR-143 gene promoter, carrying the polymorphism rs353292. The incidence of genotype CC in the RPL group was statistically significantly higher than in control group (p < 0.0001). Allele C (CT + CC) in the control group was found in 47.36%, and in the RPL group was found in 68.17% (p = 0.006). SNP rs353292 T>C was associated with increased risk of recurrent pregnancy loss. The calculated odds ratio for CT + CC vs. TT and for CC vs. TT were significant higher (p = 0.0028 and p < 0.0001, respectively). The study results suggest that the rs353292 polymorphism is associated with a statistically significant increase in RPL prevalence. The present study provides additional evidence in favor of a shared pathophysiological mechanism that contributes to both RPLs, potentially through inflammatory processes and epithelial–mesenchymal transition dysregulation. Full article

(This article belongs to the Special Issue Molecular Advances in Obstetrical and Gynaecological Disorders)

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13 pages, 1259 KiB

Open AccessArticle

Arsenic Methyltransferase and Apolipoprotein E Polymorphism in Pregnant Women Exposed to Inorganic Arsenic in Drinking Water in Western Romania

by Laura Ancuta Pop, Ioana Berindan-Neagoe, Michael S. Bloom, Iulia Adina Neamtiu, Cecilia Bica and Eugen S. Gurzau

Int. J. Mol. Sci. 2024, 25(6), 3349; https://doi.org/10.3390/ijms25063349 - 15 Mar 2024

Viewed by 1365

Abstract

Previous studies have shown that inorganic arsenic (iAs) exposure may be associated with genotoxic and cytotoxic effects. The aim of this study was to evaluate the relationship between several polymorphisms in AS3MT and APOE genes and urinary As and the relationship between these polymorphisms and pregnancy loss. We determined urinary As concentrations and performed genotyping analysis in 50 cases of spontaneous pregnancy loss and 50 controls, matched to cases on gestational age. The most frequently identified AS3MT polymorphisms in both cases and controls were in rs10748835 (80% cases and 68% controls), rs3740400 (78% cases and 64% controls), rs7085104 (74% cases and 48% controls), and rs1046778 (62% cases and 54% controls). We identified 30 different haplotypes in AS3MT SNPs, with four predominant haplotypes (>8%). Cases with Haplotype 1 had four-fold higher urinary DMA and two-fold higher MMA concentration than those without this haplotype, the MMA levels were lower in cases and controls with Haplotype 4 compared to Haplotype 1, and the DMA levels were significantly lower in cases with Haplotype 4 compared to Haplotype 3. Cases with Haplotype 1 had higher levels of all analyzed biomarkers, suggesting that Haplotype 1 may be associated with greater exposure to iAs and tobacco smoke. Our results suggest the importance of the AS3MT gene in iAs metabolism among pregnant women with low-level drinking water iAs exposure. Full article

(This article belongs to the Special Issue Molecular Advances in Obstetrical and Gynaecological Disorders)

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Review

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13 pages, 273 KiB

Open AccessReview

Platelet-Rich Plasma and Electrochemical Biosensors: A Novel Approach to Ovarian Function Evaluation and Diagnostics

by Tatjana Ivaskiene, Greta Kaspute, Egle Bareikiene and Urte Prentice

Int. J. Mol. Sci. 2025, 26(5), 2317; https://doi.org/10.3390/ijms26052317 - 5 Mar 2025

Viewed by 768

Abstract

Preserving ovarian function is important to women’s reproductive health. It is necessary for fertility and maintaining the overall hormonal balance. Platelet-rich plasma (PRP) is an autologous plasma containing a predominately platelet concentrate prepared from fresh blood. It has been observed that PRP injections into the ovary can renew the functional cells of the cortical layer of the ovary follicles and reactivate the production of sex hormones. It may improve a woman’s fertility in the case of premature ovarian failure, the condition after chemotherapy treatment, or during the climacteric period. The main markers to evaluate the procedure’s success are elevated anti-Müllerin hormone and enlarged count level of atrial follicles in ovaries. The aim of this review is to identify the ovarian PRP procedure success markers and point out the electrochemical sensor techniques. Literature was selected depending on including and excluding criteria; studies were sorted by topics in two blocks: PRP biomarkers and electrochemistry. As PRP acts as a regenerative care, electrochemical biosensors can provide accurate, real-time data to evaluate the biological response to PRP therapy. The biosensors’ ability to monitor hormonal levels and follicle development serves as objective markers of the effectiveness of PRP in restoring ovarian function. Together, these approaches enable a more precise evaluation of ovarian health and fertility outcomes after PRP intervention. Full article

(This article belongs to the Special Issue Molecular Advances in Obstetrical and Gynaecological Disorders)

30 pages, 1215 KiB

Open AccessReview

Vitamin D in Reproductive Health Disorders: A Narrative Review Focusing on Infertility, Endometriosis, and Polycystic Ovarian Syndrome

by Ximena A. van Tienhoven, Jimena Ruiz de Chávez Gascón, Gabriela Cano-Herrera, José Antonio Sarkis Nehme, Ariela A. Souroujon Torun, Maria Fernanda Bautista Gonzalez, Felipe Esparza Salazar, Ana Sierra Brozon, Eder Gabriel Rivera Rosas, Dante Carbajal Ocampo and Ramiro Cabrera Carranco

Int. J. Mol. Sci. 2025, 26(5), 2256; https://doi.org/10.3390/ijms26052256 - 3 Mar 2025

Viewed by 2318

Abstract

Vitamin D (VD) is a fat-soluble steroid hormone with essential physiological functions beyond calcium and bone metabolism. In recent years, its role in women’s reproductive health has gained attention, influencing ovarian function, follicular development, endometrial receptivity, and steroid hormone regulation. VD deficiency has been linked to reproductive disorders such as polycystic ovarian syndrome (PCOS), endometriosis, and infertility. Studies indicate that up to 40–50% of healthy pregnant women have insufficient VD levels, which may contribute to adverse pregnancy outcomes and reduced fertility. With growing evidence connecting VD to reproductive health, this review examines its molecular and endocrine mechanisms in fertility, endometriosis, and PCOS. It explores VD’s therapeutic potential and its implications for improving clinical approaches and future research in reproductive medicine. Maintaining adequate VD levels is crucial for ovarian function, immune modulation in reproductive tissues, and overall fertility. Its deficiency is associated with insulin resistance, hormonal imbalances, and inflammatory processes, which contribute to reproductive pathophysiology. Establishing reference values for VD in reproductive medicine is essential for optimizing fertility treatments and improving clinical outcomes. This review synthesizes current research on VD’s role in reproductive health and highlights the need for further investigation into its therapeutic applications. Full article

(This article belongs to the Special Issue Molecular Advances in Obstetrical and Gynaecological Disorders)

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31 pages, 2005 KiB

Open AccessReview

Surface Molecular Markers for the Isolation of Viable Fibroblast Subpopulations in the Female Reproductive Tract: A Comprehensive Review

by Krzysztof Łuszczyński, Michał Komorowski, Marta Soszyńska, Paulina Lewandowska, Robert Zdanowski, Monika Szafarowska, Paweł Kamiński, Marcin Niemcewicz, Jacek Malejczyk, Anna Lutyńska and Aneta Ścieżyńska

Int. J. Mol. Sci. 2025, 26(1), 233; https://doi.org/10.3390/ijms26010233 - 30 Dec 2024

Viewed by 1384

Abstract

Advancements in single-cell analyzis technologies, particularly single-cell RNA sequencing (scRNA-seq) and Fluorescence-Activated Cell Sorting (FACS), have enabled the analyzis of cellular diversity by providing resolutions that were not available previously. These methods enable the simultaneous analyzis of thousands of individual transcriptomes, facilitating the classification of cells into distinct subpopulations, based on transcriptomic differences, adding a new level of complexity to biomolecular and medical research. Fibroblasts, despite being one of the most abundant cell types in the human body and forming the structural backbone of tissues and organs, remained poorly characterized for a long time. This is largely due to the high morphological similarity between different types of fibroblasts and the lack of specific markers to identify distinct subpopulations. Once thought to be cells responsible solely for the synthesis of extracellular matrix (ECM) components, fibroblasts are now recognized as active participants in diverse physiological processes, including inflammation and antimicrobial responses. However, defining the molecular profile of fibroblast subpopulations remains a significant challenge. In this comprehensive review, which is based on over two thousand research articles, we focus on the identification and characterization of fibroblast subpopulations and their specific surface markers, with an emphasis on their potential as molecular targets for selective cell isolation. By analyzing surface markers, alongside intra- and extracellular protein profiles, we identified multiple fibroblast subtypes within the female reproductive system. These subtypes exhibit distinct molecular signatures and functional attributes, shaped by their anatomical localization and the surrounding physiological or pathological conditions. Our findings underscore the heterogeneity of fibroblasts and their diverse roles in various biological contexts. This improved understanding of fibroblast subpopulations paves the way for innovative diagnostic and therapeutic strategies, offering the potential for precision targeting of specific fibroblast subsets in clinical applications. Full article

(This article belongs to the Special Issue Molecular Advances in Obstetrical and Gynaecological Disorders)

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