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Molecular Pathophysiology of Uterine and Ovarian Diseases and Dysfunction 4.0

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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: closed (30 April 2024) | Viewed by 5843

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Special Issue Editor

Prof. Dr. Seung-Yup Ku

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Guest Editor

Department of Obstetrics and Gynecology, Seoul National University Hospital, Seoul National University College of Medicine, 28 Yonkeun-dong, Chongno-gu, Seoul 110-744, Republic of Korea
Interests: RNA; ovarian; uterus
Special Issues, Collections and Topics in MDPI journals

Special Issue Information

Dear Colleagues,

Reproduction is a very critical scientific phenomenon, tied to the origin of mankind. Successful or failed pregnancy, menstrual dysfunction, and the tumorigenesis of female reproductive organs currently offer numerous challenges for meeting clinically unmet needs, and often require advanced therapeutic strategies.

There has been exciting progress in understanding the molecular pathophysiology of various uterine and ovarian diseases and dysfunction in recent years. Genetic or epigenetic alterations represent novel diagnostic and prognostic molecular markers and therapeutic targets for these diseases and dysfunction. To date, specific biomarkers, as well as genetic or epigenetic alterations, have been identified.

This Special Issue of IJMS is searching for answers to some of the above-mentioned questions, in an attempt to provide reproductive biomedical scientists and clinicians with novel answers that should lead to a better understanding of these prevalent and serious universal diseases and dysfunction. Studies using clinical samples, and animal or cell culture models to investigate the molecular pathophysiology of uterine and ovarian diseases and dysfunction will be published.

IJMS looks forward to receiving excellent contributions from all types of investigators of female reproductive tract dysfunction and diseases.

Prof. Dr. Seung-Yup Ku
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 100 words) can be sent to the Editorial Office for announcement on this website.

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

uterine tumor
ovarian tumor
hormonal dysfunction
polycystic ovary syndrome
endometriosis
menopause
infertility
pregnancy
abortion
assisted reproduction
pluripotent stem cell
tissue engineering

Published Papers (4 papers)

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Research

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19 pages, 5912 KiB

Open AccessArticle

β-Nicotinamide Mononucleotide Alleviates Hydrogen Peroxide-Induced Cell Cycle Arrest and Death in Ovarian Granulosa Cells

by Yunduan Wang, Qiao Li, Zifeng Ma, Hongmei Xu, Feiyu Peng, Bin Chen, Bo Ma, Linmei Qin, Jiachen Lan, Yueyue Li, Daoliang Lan, Jian Li, Shujin Wang and Wei Fu

Int. J. Mol. Sci. 2023, 24(21), 15666; https://doi.org/10.3390/ijms242115666 - 27 Oct 2023

Cited by 2 | Viewed by 1315

Abstract

Maintaining normal functions of ovarian granulosa cells (GCs) is essential for oocyte development and maturation. The dysfunction of GCs impairs nutrition supply and estrogen secretion by follicles, thus negatively affecting the breeding capacity of farm animals. Impaired GCs is generally associated with declines in Nicotinamide adenine dinucleotide (NAD⁺) levels, which triggers un-controlled oxidative stress, and the oxidative stress, thus, attack the subcellular structures and cause cell damage. β-nicotinamide mononucleotide (NMN), a NAD⁺ precursor, has demonstrated well-known antioxidant properties in several studies. In this study, using two types of ovarian GCs (mouse GCs (mGCs) and human granulosa cell line (KGN)) as cell models, we aimed to investigate the potential effects of NMN on gene expression patterns and antioxidant capacity of both mGCs and KGN that were exposed to hydrogen peroxide (H₂O₂). As shown in results of the study, mGCs that were exposed to H₂O₂ significantly altered the gene expression patterns, with 428 differentially expressed genes (DEGs) when compared with those of the control group. Furthermore, adding NMN to H₂O₂-cultured mGCs displayed 621 DEGs. The functional enrichment analysis revealed that DEGs were mainly enriched in key pathways like cell cycle, senescence, and cell death. Using RT-qPCR, CCK8, and β-galactosidase staining, we found that H₂O₂ exposure on mGCs obviously reduced cell activity/mRNA expressions of antioxidant genes, inhibited cell proliferation, and induced cellular senescence. Notably, NMN supplementation partially prevented these H₂O₂-induced abnormalities. Moreover, these similar beneficial effects of NMN on antioxidant capacity were confirmed in the KGN cell models that were exposed to H₂O₂. Taken together, the present results demonstrate that NMN supplementation protects against H₂O₂-induced impairments in gene expression pattern, cell cycle arrest, and cell death in ovarian GCs through boosting NAD⁺ levels and provide potential strategies to ameliorate uncontrolled oxidative stress in ovarian GCs. Full article

(This article belongs to the Special Issue Molecular Pathophysiology of Uterine and Ovarian Diseases and Dysfunction 4.0)

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13 pages, 2339 KiB

Open AccessArticle

Is HOXA5 a Novel Prognostic Biomarker for Uterine Corpus Endometrioid Adenocarcinoma?

by Changho Song, Kyoung Bo Kim, Gi Su Lee, Soyoung Shin and Byoungje Kim

Int. J. Mol. Sci. 2023, 24(19), 14758; https://doi.org/10.3390/ijms241914758 - 29 Sep 2023

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Abstract

Endometrial cancer (EC) is one of the most pervasive malignancies in females worldwide. HOXA5 is a member of the homeobox (HOX) family and encodes the HOXA5 protein. HOXA5 is associated with various cancers; however, its association with EC remains unclear. This study aimed to determine the association between HOXA5 gene expression and the prognosis of endometrioid adenocarcinoma, a subtype of EC (EAEC). Microarray data of HOXA5 were collected from the Gene Expression Omnibus datasets, consisting of 79 samples from GSE17025 and 20 samples from GSE29981. RNA-sequencing, clinical, and survival data on EC were obtained from The Cancer Genome Atlas cohort. Survival analysis revealed that HOXA5 overexpression was associated with poor overall survival in patients with EAEC (p = 0.044, HR = 1.832, 95% CI = 1.006–3.334). Cox regression analysis revealed that HOXA5 was an independent risk factor for poor prognosis in EAEC. The overexpression of HOXA5 was associated with a higher histological grade of EAEC, and it was also associated with TP53 mutation or the high copy number of EC. Our findings suggest the potential of HOXA5 as a novel biomarker for predicting poor survival outcomes in patients with EAEC. Full article

(This article belongs to the Special Issue Molecular Pathophysiology of Uterine and Ovarian Diseases and Dysfunction 4.0)

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15 pages, 2556 KiB

Open AccessArticle

Evaluation of Immune Infiltrates in Ovarian Endometriosis and Endometriosis-Associated Ovarian Cancer: Relationship with Histological and Clinical Features

by Emanuela Spagnolo, Alejandra Martinez, Andrea Mascarós-Martínez, Josep Marí-Alexandre, María Carbonell, Eva González-Cantó, Eva Manuela Pena-Burgos, Bárbara Andrea Mc Cormack, Sarai Tomás-Pérez, Juan Gilabert-Estellés, Ana López-Carrasco, Paula Hidalgo, Martina Aida Ángeles, Andrés Redondo, Alejandro Gallego and Alicia Hernández

Int. J. Mol. Sci. 2023, 24(15), 12083; https://doi.org/10.3390/ijms241512083 - 28 Jul 2023

Cited by 1 | Viewed by 1441

Abstract

Background: the association between ovarian endometriosis (OE) and endometriosis-associated ovarian cancer (EAOC) is extensively documented, and misfunction of the immune system might be involved. The primary objective of this study was to identify and compare the spatial distribution of tumour-infiltrating lymphocytes (TILs) and tumour-associated macrophages (TAMs) in OE and EAOC. Secondary objectives included the analysis of the relationship between immunosuppressive populations and T-cell exhaustion markers in both groups. Methods: TILs (CD3, CD4, and CD8) and macrophages (CD163) were assessed by immunochemistry. Exhaustion markers (PD-1, TIM3, CD39, and FOXP3) and their relationship with tumour-associated macrophages (CD163) were assessed by immunofluorescence on paraffin-embedded samples from n = 43 OE and n = 54 EAOC patients. Results: we observed a predominantly intraepithelial CD3+ distribution in OE but both an intraepithelial and stromal pattern in EAOC (p < 0.001). TILs were more abundant in OE (p < 0.001), but higher TILs significantly correlated with a longer overall survival and disease-free survival in EAOC (p < 0.05). CD39 and FOXP3 significantly correlated with each other and CD163 (p < 0.05) at the epithelial level in moderate/intense CD4 EAOC, whereas in moderate/intense CD8+, PD-1+ and TIM3+ significantly correlated (p = 0.009). Finally, T-cell exhaustion markers FOXP3-CD39 were decreased and PD-1-TIM3 were significantly increased in EAOC (p < 0.05). Conclusions: the dysregulation of TILs, TAMs, and T-cell exhaustion might play a role in the malignization of OE to EAOC. Full article

(This article belongs to the Special Issue Molecular Pathophysiology of Uterine and Ovarian Diseases and Dysfunction 4.0)

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Review

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23 pages, 1032 KiB

Open AccessReview

Effects of Melatonin, GM-CSF, IGF-1, and LIF in Culture Media on Embryonic Development: Potential Benefits of Individualization

by Jung-Won Choi, Sung-Woo Kim, Hee-Sun Kim, Moon-Joo Kang, Sung-Ah Kim, Ji-Yeon Han, Hoon Kim and Seung-Yup Ku

Int. J. Mol. Sci. 2024, 25(2), 751; https://doi.org/10.3390/ijms25020751 - 06 Jan 2024

Cited by 1 | Viewed by 1352

Abstract

The implantation of good-quality embryos to the receptive endometrium is essential for successful live birth through in vitro fertilization (IVF). The higher the quality of embryos, the higher the live birth rate per cycle, and so efforts have been made to obtain as many high-quality embryos as possible after fertilization. In addition to an effective controlled ovarian stimulation process to obtain high-quality embryos, the composition of the embryo culture medium in direct contact with embryos in vitro is also important. During embryonic development, under the control of female sex hormones, the fallopian tubes and endometrium create a microenvironment that supplies the nutrients and substances necessary for embryos at each stage. During this process, the development of the embryo is finely regulated by signaling molecules, such as growth factors and cytokines secreted from the epithelial cells of the fallopian tube and uterine endometrium. The development of embryo culture media has continued since the first successful human birth through IVF in 1978. However, there are still limitations to mimicking a microenvironment similar to the reproductive organs of women suitable for embryo development in vitro. Efforts have been made to overcome the harsh in vitro culture environment and obtain high-quality embryos by adding various supplements, such as antioxidants and growth factors, to the embryo culture medium. Recently, there has been an increase in the number of studies on the effect of supplementation in different clinical situations such as old age, recurrent implantation failure (RIF), and unexplained infertility; in addition, anticipation of the potential benefits from individuation is rising. This article reviews the effects of representative supplements in culture media on embryo development. Full article

(This article belongs to the Special Issue Molecular Pathophysiology of Uterine and Ovarian Diseases and Dysfunction 4.0)

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