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Molecular Research in Gynecological Diseases—2nd Edition

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 August 2025 | Viewed by 3461

Special Issue Editor

Special Issue Information

Dear Colleagues,

The Centers for Disease Control and Prevention recognizes five types of gynecologic cancers as follows: cervical cancer, ovarian cancer, uterine cancer, vaginal cancer, and vulvar cancer. GLOBOCAN 2020 reports that these cancers represent the fifth leading cause of cancer-related deaths. Notably, a screening test that can detect gynecological cancers in their early stages exists only for cervical cancer. Consequently, screening tests for these cancers are a high priority. This is especially true for ovarian cancers, which are associated with poor outcomes. The American Cancer Society estimates that, in 2023, in the United States, 19,710 women will be diagnosed with ovarian cancer, and 13,270 women will die from ovarian cancer.

It is well known that benign gynecological diseases affect a huge number of women. It is estimated that adenomyosis and leiomyomas (also known as uterine fibroids) each affect approximately 20% of women who are of a reproductive age, and that endometriosis and polycystic ovary syndrome (PCOS) each affect approximately 10% of women who are of a reproductive age. Other benign gynecological conditions also affect a significant percentage of women. However, benign gynecological diseases are oftentimes ignored. For example, in reference to endometriosis, the New York Times (27 April 2021) states “Yet, it suffers from a branding problem: It falls into the abyss of “women’s diseases” (overlooked), diseases that do not kill you (unimportant), and menstrual problems (taboo)”, and the Guardian (2 June 2022) states “Doctors’ routine dismissal of women’s debilitating health problems as “benign” has contributed to gynaecology waiting lists soaring by 60% to more than half a million patients, a senior health leader has said”. While benign gynecological diseases are generally not fatal, they have a significant adverse effect on the quality of life of millions of women.

The International Journal of Molecular Sciences introduces this Special Issue to create a collection of papers regarding specific topics and to build a community of authors and readers, enabling the discussion of the latest research and the developing of new ideas and research directions. This Special Issue is soliciting review articles, original research articles, and short communications regarding the molecular aspects of gynecological diseases. These include identifying markers that can be used in the screening and diagnosis of relevant gynecological diseases, investigating DNA mutations and cellular signaling pathways that lead to the development of the disease, investigating the involvement of the microbiota in various gynecological diseases, and identifying targets that can be used in the treatment of the disease, including potential targets for CRISPR-mediated therapies.

Dr. David B. Alexander
Guest Editor

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Keywords

  • malignant gynecological diseases
  • screening for gynecological cancers
  • benign gynecological conditions
  • screening for benign gynecological diseases
  • endometriosis
  • polycystic ovaries syndrome
  • ovarian cysts
  • uterine fibroids
  • leiomyomas
  • adenomyosis
  • pelvic inflammatory disease
  • vaginitis
  • vaginal dysbiosis
  • treatment targets for gynecological diseases

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Related Special Issue

Published Papers (3 papers)

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23 pages, 5006 KiB  
Article
Expression, Distribution and Function of the Transient Receptor Potential Vanilloid Type 1 (TRPV1) in Endometrial Cancer
by Thangesweran Ayakannu, Anthony H. Taylor and Justin C. Konje
Int. J. Mol. Sci. 2025, 26(7), 3104; https://doi.org/10.3390/ijms26073104 - 27 Mar 2025
Viewed by 443
Abstract
The transient receptor potential vanilloid 1 receptor (TRPV1) is a calcium-sensitive membrane receptor activated by capsaicin and the endocannabinoid, anandamide (AEA). Once activated in vitro, endometrial cancer (EC) cell growth appears to be inhibited through increased apoptosis, but the mechanism remains unclear. Our [...] Read more.
The transient receptor potential vanilloid 1 receptor (TRPV1) is a calcium-sensitive membrane receptor activated by capsaicin and the endocannabinoid, anandamide (AEA). Once activated in vitro, endometrial cancer (EC) cell growth appears to be inhibited through increased apoptosis, but the mechanism remains unclear. Our aim was to investigate the expression and distribution of TRPV1 in normal and cancerous endometria and to determine the precise in vitro mechanism of decreased EC cellular growth. TRPV1 expression in patients with endometrial carcinoma (15 Type 1 EC, six Type 2 EC) and six normal patients (atrophic endometria) was assessed using quantitative RT-PCR and immunohistochemistry (IHC). Additionally, immunohistochemical staining for the proliferation marker Ki-67, the pro-apoptotic marker BAX and the anti-apoptotic marker Bcl-2 were explored. TRPV1 transcript (p = 0.0054) and immunoreactive protein (p < 0.0001) levels were significantly reduced in all EC tissues when compared to control (atrophic) endometria. The almost 50% reduction in TRPV1 transcript levels was mirrored by an almost complete loss of immunoreactive TRPV1 protein. The increased proliferation (Ki-67) of EC tissues correlated with the expression of mutated BAX and inversely correlated to Bcl-2, but only in Type 2 EC samples. In vitro, AEA caused a decrease in Ishikawa cell numbers, whilst capsaicin did not, suggesting the anti-proliferative effect of AEA in EC cells is not via the TRPV1 receptor. In conclusion, the loss of TRPV1 expression in vivo plays a role in the aetiopathogenesis of EC. Activation of cells by AEA also probably promotes EC cell loss through a pro-apoptotic mechanism not involving TRPV1. Full article
(This article belongs to the Special Issue Molecular Research in Gynecological Diseases—2nd Edition)
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21 pages, 2950 KiB  
Article
In Vitro Effect of Estrogen and Progesterone on Cytogenetic Profile of Uterine Leiomyomas
by Alla S. Koltsova, Anna A. Pendina, Olga V. Malysheva, Ekaterina D. Trusova, Dmitrii A. Staroverov, Maria I. Yarmolinskaya, Nikolai I. Polenov, Andrey S. Glotov, Igor Yu. Kogan and Olga A. Efimova
Int. J. Mol. Sci. 2025, 26(1), 96; https://doi.org/10.3390/ijms26010096 - 26 Dec 2024
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Abstract
In the present study, we aimed to investigate intratumoral karyotype diversity as well as the estrogen/progesterone effect on the cytogenetic profile of uterine leiomyomas (ULs). A total of 15 UL samples obtained from 15 patients were cultured in the media supplemented with estrogen [...] Read more.
In the present study, we aimed to investigate intratumoral karyotype diversity as well as the estrogen/progesterone effect on the cytogenetic profile of uterine leiomyomas (ULs). A total of 15 UL samples obtained from 15 patients were cultured in the media supplemented with estrogen and/or progesterone and without adding hormones. Conventional cytogenetic analysis of culture samples revealed clonal chromosomal abnormalities in 11 out of 15 ULs. Cytogenetic findings were presented by simple and complex chromosomal rearrangements (64% and 36% of cases, respectively) verified through FISH and aCGH. In most ULs with complex chromosomal rearrangements, the breakpoints did not feature clusterization on a single chromosome but were evenly distributed across rearranged chromosomes. The number of breakpoints showed a strong positive correlation with the number of rearranged chromosomes. Moreover, both abovementioned parameters were in a linear dependency from the number of karyotypically different clones per UL. This suggests that complex chromosomal rearrangements in ULs predominantly originate through sequential events rather than one hit. The results of UL cytogenetic analysis depended on the presence of estrogen and/or progesterone in the culture medium. The greatest variety of cytogenetically different cell clones was detected in the samples cultured without hormone supplementation. Their counterparts cultured with progesterone supplementation showed a sharp decrease in clone number, whereas such a decrease induced by estrogen or estrogen–progesterone supplementation was insignificant. These findings suggest that estrogen–progesterone balance is crucial for forming a UL cytogenetic profile, which, in turn, may underlie the unique response of the every karyotypically abnormal UL to medications. Full article
(This article belongs to the Special Issue Molecular Research in Gynecological Diseases—2nd Edition)
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13 pages, 1982 KiB  
Article
Deciphering Folate Receptor alphaGene Expression and mRNA Signatures in Ovarian Cancer: Implications for Precision Therapies
by Maria Kfoury, Pascal Finetti, Emilie Mamessier, François Bertucci and Renaud Sabatier
Int. J. Mol. Sci. 2024, 25(22), 11953; https://doi.org/10.3390/ijms252211953 - 7 Nov 2024
Viewed by 1685
Abstract
Antibody–drug conjugates targeting folate receptor alpha (FRα) are a promising treatment for platinum-resistant ovarian cancer (OC) with high FRα expression. Challenges persist in accurately assessing FRα expression levels. Our study aimed to better elucidate FRα gene expression and identify mRNA signatures in OC. [...] Read more.
Antibody–drug conjugates targeting folate receptor alpha (FRα) are a promising treatment for platinum-resistant ovarian cancer (OC) with high FRα expression. Challenges persist in accurately assessing FRα expression levels. Our study aimed to better elucidate FRα gene expression and identify mRNA signatures in OC. We pooled OC gene expression data from 16 public datasets, encompassing 1832 OC and 30 normal ovarian tissues. Additional data included DNA copy number and methylation data from TCGA and protein data from 363 cancer cell lines from the Broad Institute Cancer Cell Line Encyclopedia. FOLR1 mRNA expression was significantly correlated with protein expression in pan-cancer cell lines and ovarian cancer cell lines. FOLR1 expression was higher in OC samples than in normal ovarian tissues (OR = 3.88, p = 6.97 × 10−12). Patients with high FOLR1 expression were more likely to be diagnosed with serous histology, FIGO stage III–IV, and high-grade tumors; however, nearly similar percentages of patients with low FOLR1 expression were also diagnosed with these features. FOLR1 mRNA expression was not correlated with platinum sensitivity or complete surgery, nor with prognosis. However, we identified a 187-gene signature associated with high FOLR1 expression that was significantly associated with improved survival (HR = 0.71, p = 1.18 × 10−6), independently from clinicopathological features. We identified a gene expression signature correlated to high FRα expression and OC prognosis, which may be used to refine therapeutic strategies targeting FRα in OC. These findings warrant validation in larger cohorts. Full article
(This article belongs to the Special Issue Molecular Research in Gynecological Diseases—2nd Edition)
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