Copper homeostasis and cuproptosis in gynecological disorders: Pathogenic insights and therapeutic implications.

This review comprehensively explores the complex role of copper homeostasis in female reproductive system diseases. As an essential trace element, copper plays a crucial role in various biological functions. Its dysregulation is increasingly recognized as a pivotal factor in the pathogenesis of gynecological disorders. We investigate how copper impacts these diseases, focusing on aspects like oxidative stress, inflammatory responses, immune function, estrogen levels, and angiogenesis. The review highlights significant changes in copper levels in diseases such as cervical, ovarian, endometrial cancer, and endometriosis, underscoring their potential roles in disease mechanisms and therapeutic exploration. The recent discovery of 'cuproptosis,' a novel cell death mechanism induced by copper ions, offers a fresh molecular perspective in understanding these diseases. The review also examines genes associated with cuproptosis, particularly those related to drug resistance, suggesting new strategies to enhance traditional therapy effectiveness. Additionally, we critically evaluate current therapeutic approaches targeting copper homeostasis, including copper ionophores, chelators, and nanoparticles, emphasizing their emerging potential in gynecological disease treatment. This article aims to provide a comprehensive overview of copper's role in female reproductive health, setting the stage for future research to elucidate its mechanisms and develop targeted therapeutic strategies.

Deciphering the potential of proteomic-based biomarkers in women's reproductive diseases: empowering precision medicine in gynecology.

CONTEXT: Gynecological disorders represent a complex set of malignancies that result from a diverse array of molecular changes affecting the lives of over a million women worldwide. Ovarian, Endometrial, and Cervical cancers, Endometriosis, PCOS are the most prevalent ones that pose a grave threat to women's health. Proteomics has emerged as an invaluable tool for developing novel biomarkers, screening methods, and targeted therapeutic agents for gynecological disorders. Some of these biomarkers have been approved by the FDA, but regrettably, they have a constrained diagnostic accuracy in early-stage diagnosis as all of these biomarkers lack sensitivity and specificity. Lately, high-throughput proteomics technologies have made significant strides, allowing for identification of potential biomarkers with improved sensitivity and specificity. However, limited successes have been shown with translation of these discoveries into clinical practice. OBJECTIVE: This review aims to provide a comprehensive overview of the current and potential protein biomarkers for gynecological cancers, endometriosis and PCOS, discusses recent advances and challenges, and highlights future directions for the field. CONCLUSION: We propose that proteomics holds great promise as a powerful tool to revolutionize the fight against female reproductive diseases and can ultimately improve personalized patient outcomes in women's biomedicine.

The Role of ApoE Expression and Variability of Its Glycosylation in Human Reproductive Health in the Light of Current Information.

Apolipoprotein E (ApoE), a 34-kDa glycoprotein, as part of the high-density lipoprotein (HDL), has antioxidant, anti-inflammatory and antiatherogenic properties. The variability of ApoE expression in the course of some female fertility disorders (endometriosis, POCS), and other gynecological pathologies such as breast cancer, choriocarcinoma, endometrial adenocarcinoma/hyperplasia and ovarian cancer confirm the multidirectional biological function of ApoE, but the mechanisms of its action are not fully understood. It is also worth taking a closer look at the associations between ApoE expression, the type of its genotype and male fertility disorders. Another important issue is the variability of ApoE glycosylation. It is documented that the profile and degree of ApoE glycosylation varies depending on where it occurs, the type of body fluid and the place of its synthesis in the human body. Alterations in ApoE glycosylation have been observed in the course of diseases such as preeclampsia or breast cancer, but little is known about the characteristics of ApoE glycans analyzed in human seminal and blood serum/plasma in the context of male reproductive health. A deeper analysis of ApoE glycosylation in the context of female and male fertility will both enable us to broaden our knowledge of the biochemical and cellular mechanisms in which glycans participate, having a direct or indirect relationship with the fertilization process, and also give us a chance of contributing to the enrichment of the diagnostic panel in infertile women and men, which is particularly important in procedures involved in assisted reproductive techniques. Moreover, understanding the mechanisms of glycoprotein glycosylation related to the course of various diseases and conditions, including infertility, and the interactions between glycans and their specific ligands may provide us with an opportunity to interfere with their course and thus develop new therapeutic strategies. This brief overview details some of the recent advances, mainly from the last decade, in understanding the associations between ApoE expression and some female and male fertility problems, as well as selected female gynecological diseases and male reproductive tract disorders. We were also interested in how ApoE glycosylation changes influence biological processes in the human body, with special attention to human fertility.

Ischemia-modified albumin in gynecology.

Background: Ischemia-modified albumin (IMA) is an oxidative stress marker used to assess the presence and severity of oxidative stress. This marker was first used for early diagnosis of myocardial ischemia. Materials & methods: A variety of IMA studies were carried out to show the effect of oxidative stress on gynecological disorders. Conclusion: This analysis summarizes the literature by conducting electronic research on the relationship between IMA and gynecological disorders.

Mouse model of menstruation: An indispensable tool to investigate the mechanisms of menstruation and gynaecological diseases (Review).

Abnormal menstruation may result in several pathological alterations and gynaecological diseases, including endometriosis, menstrual pain and miscarriage. However, the pathogenesis of menstruation remains unclear due to the limited number of animal models available to study the menstrual cycle. In recent years, an effective, reproducible, and highly adaptive mouse model to study menstruation has been developed. In this model, progesterone and oestrogen were administered in cycles following the removal of ovaries. Subsequently, endometrial decidualisation was induced using sesame oil, followed by withdrawal of progesterone administration. Vaginal bleeding in mice is similar to that in humans. Therefore, the use of mice as a model organism to study the mechanism of menstruation and gynaecological diseases may prove to be an important breakthrough. The present review is focussed ond the development and applications of a mouse model of menstruation. Furthermore, various studies have been described to improve this model and the research findings that may aid in the treatment of menstrual disorders in women are presented.

90 YEARS OF PROGESTERONE: Selective progesterone receptor modulators in gynaecological therapies.

Abnormal uterine bleeding (AUB) is a chronic, debilitating and common condition affecting one in four women of reproductive age. Current treatments (conservative, medical and surgical) may be unsuitable, poorly tolerated or may result in loss of fertility. Selective progesterone receptor modulators (SPRMs) influence progesterone-regulated pathways, a hormone critical to female reproductive health and disease; therefore, SPRMs hold great potential in fulfilling an unmet need in managing gynaecological disorders. SPRMs in current clinical use include RU486 (mifepristone), which is licensed for pregnancy interruption, and CDB-2914 (ulipristal acetate), licensed for managing AUB in women with leiomyomas and in a higher dose as an emergency contraceptive. In this article, we explore the clinical journey of SPRMs and the need for further interrogation of this class of drugs with the ultimate goal of improving women's quality of life.

NLRP3 Inflammasome and Its Critical Role in Gynecological Disorders and Obstetrical Complications.

Inflammasomes, intracellular, multimeric protein complexes, are assembled when damage signals stimulate nucleotide-binding oligomerization domain receptors (NLRs). Several inflammasomes have been reported, including the NOD-, LRR- and pyrin domain-containing protein 3 (NLRP3), NLRP1, NLRP7, ice protease-activating factor (IPAF), absent in melanoma 2 (AIM2) and NLR family CARD domain-containing protein 4 (NLRC4). Among these inflammasomes, the NLRP3 inflammasome is the most well-studied in terms of structure and function. Unlike other inflammasomes that can only be activated by a finite number of pathogenic microorganisms, the NLRP3 inflammasome can be activated by the imbalance of the internal environment and a large number of metabolites. The biochemical function of NLRP3 inflammasome is to activate cysteine-requiring aspartate proteinase-1 (caspase-1), which converts pro-IL-1ß and pro-IL-18 into their active forms, namely, IL-1ß and IL-18, which are then released into the extracellular space. The well-established, classic role of NLRP3 inflammasome has been implicated in many disorders. In this review, we discuss the current understanding of NLRP3 inflammasome and its critical role in gynecological disorders and obstetrical complications.

GLUT1 expression in human papillomavirus-positive anogenital lesions.

BACKGROUND: GLUT1, an ubiquitous glucose transporter in the mammalian cells, is upregulated in many tumours, including human papillomavirus (HPV)-induced head and neck or cervical cancer. OBJECTIVE: To study in anogenital lesions whether or not GLUT1 expression correlates with genomic high-risk HPV integration, the first step in neoplastic transformation. METHODS: Forty-three HPV-positive biopsies positive for either low-risk or high-risk HPV were selected. Paraffin sections adjacent to those tested for the presence of HPV were processed for GLUT1 immunocytochemistry. GLUT1 expression was analysed by two histologists, blinded to HPV type and status and then compared with HPV typing results. RESULTS: Two main staining patterns were observed, either staining from the basal to the granular layer or staining of superficial layers only. The first staining pattern corresponded to lesions with high number of episomal HPV-positive nuclei. Superficial staining was observed in lesions with low number of episomal HPV nuclei or when high-risk HPV was integrated in the cell genome. CONCLUSION: Our results show that GLUT1 overexpression correlates with the number of episomally infected cells in the lesion, but not with the type (low or high risk) of HPV.

Chemical profliling of Dingkun Dan by ultra High performance liquid chromatography Q exactive orbitrap high resolution mass spectrometry.

Dingkun Dan (DKD) has been widely used for a variety of gynecological disease. However, the systematic analysis of the chemical constituents of DKD has not been well established because of the complexity of the formula and confidentiality. In this paper, liquid chromatography Q Exactive high resolution accurate mass spectrometry (UHPLC-QE-HRMS) with automated MetaboLynx analysis was established to characterize the chemical constituents of DKD. The analysis was performed on a Water Acquity UPLC® HSS T3 using a gradient elution system. Full scan ranged 100-1500 m/z in positive and negative ion mode combined with MS/MS fragmentation for top 5 ions was proposed for aiding the structural identification of the components. All of the peaks were tentatively characterized by not only comparing the retention time and MS data with those from reported literature and database, but also summarizing the fragmentation pathways and promoting to other ingredients identification. Additionally, the network pharmacology study had been used to analysis the identified ingredients and DKD's clinical diseases. In this work, a total of 121 components and isomers were characterized, including amino acids, phenolic acids, lactones, terpenoids, alkaloids, saponins, flavonoids, and other compounds. Network pharmacology analysis showed that identified compounds, such as ginsenosides and notoginsenosides, crocin I, echinacoside, rutin and verbascoside, could be responsible for the pharmacological activity of DKD by regulating the hormone with related metabolism pathways, estrogen signaling pathways and serotonergic synapse pathways. It could indicate that UHPLC-MS showed obvious superiority used to find the potential bioactive compounds of complicated TCM formula without the process of extraction and isolation.

Cardiometabolic Risk Factors and Benign Gynecologic Disorders.

IMPORTANCE: While it has long been known that polycystic ovarian syndrome is associated with cardiometabolic risk factors (CMRFs), there is emerging evidence that other benign gynecologic conditions, such as uterine leiomyomas, endometriosis, and even hysterectomy without oophorectomy, can be associated with CMRFs. Understanding the evidence and mechanisms of these associations can lead to novel preventive and therapeutic interventions. OBJECTIVE: This article discusses the evidence and the potential mechanisms mediating the association between CMRFs and benign gynecologic disorders. EVIDENCE ACQUISITION: We reviewed PubMed, EMBASE, Scopus, and Google Scholar databases to obtain plausible clinical and biological evidence, including hormonal, immunologic, inflammatory, growth factor-related, genetic, epigenetic, atherogenic, vitamin D-related, and dietary factors. RESULTS: Cardiometabolic risk factors appear to contribute to uterine leiomyoma pathogenesis. For example, obesity can modulate leiomyomatous cellular proliferation and extracellular matrix deposition through hyperestrogenic states, chronic inflammation, insulin resistance, and adipokines. On the other hand, endometriosis has been shown to induce systemic inflammation, thereby increasing cardiometabolic risks, for example, through inducing atherosclerotic changes. CONCLUSION AND RELEVANCE: Clinical implications of these associations are 2-fold. First, screening and early modification of CMRFs can be part of a preventive strategy for uterine leiomyomas and hysterectomy. Second, patients diagnosed with uterine leiomyomas or endometriosis can be screened and closely followed for CMRFs and cardiovascular disease.

Calcium Supplementation Alleviates High-Fat Diet-Induced Estrous Cycle Irregularity and Subfertility Associated with Concomitantly Enhanced Thermogenesis of Brown Adipose Tissue and Browning of White Adipose Tissue.

Obesity has been demonstrated as a disruptor of female fertility. Our previous study showed the antiobesity effects of calcium on HFD-fed male mice. However, the role of calcium in alleviating reproductive dysfunction of HFD-fed female mice remains unclear. Here, we found that HFD led to estrus cycle irregularity (longer cycle duration and shorter estrus period) and subfertility (longer conception time, lower fertility index, and less implantations) in mice. However, the HFD-induced reproductive abnormality was alleviated by calcium supplementation. Additionally, calcium supplementation enhanced activation/thermogenesis of BAT and browning of WAT in HFD-fed mice. Consequently, the abnormality of energy metabolism and glucose homeostasis induced by HFD were improved by calcium supplementation, with elevated metabolic rates and core temperature. In conclusion, these data showed that calcium supplementation alleviated HFD-induced estrous cycle irregularity and subfertility associated with concomitantly enhanced BAT thermogenesis and WAT browning, suggesting the potential application of calcium in improving obesity-related reproductive disorders.

A novel and compact review on the role of oxidative stress in female reproduction.

In recent years, the study of oxidative stress (OS) has become increasingly popular. In particular, the role of OS on female fertility is very important and has been focused on closely. The occurrence of OS is due to the excessive production of reactive oxygen species (ROS). ROS are a double-edged sword; they not only play an important role as secondary messengers in many intracellular signaling cascades, but they also exert indispensable effects on pathological processes involving the female genital tract. ROS and antioxidants join in the regulation of reproductive processes in both animals and humans. Imbalances between pro-oxidants and antioxidants could lead to a number of female reproductive diseases. This review focuses on the mechanism of OS and a series of female reproductive processes, explaining the role of OS in female reproduction and female reproductive diseases caused by OS, including polycystic ovary syndrome (PCOS), endometriosis, preeclampsia and so on. Many signaling pathways involved in female reproduction, including the Keap1-Nrf2, NF-κB, FOXO and MAPK pathways, which are affected by OS, are described, providing new ideas for the mechanism of reproductive diseases.

Increased expression of p16 in both oral and genital lichen planus.

BACKGROUND: Lichen Planus, LP, is an inflammatory disease of possible autoimmune origin affecting mainly oral and genital mucosa and skin. According to the WHO oral LP is considered a potentially malignant disorders. The p16 tumour suppressor protein can act as an inhibitor of cyclin dependent kinases 4 and 6 and thus down regulate cell cycle progression. Since the discovery of p16 several studies have evaluated its expression in various forms of human cancers. The aim of this study was to evaluate and compare the expression of p16 in oral and genital LP and corresponding healthy mucosa. MATERIAL AND METHODS: A total of 76 cases of oral LP (OLP), 34 cases of genital LP (GLP), 12 cases of healthy oral and 9 cases of healthy genital mucosa were analysed by the use of immunohistochemistry. RESULTS: Data showed p16 to be highly expressed in both oral and genital LP, higher than in oral (p=0.000), and genital controls (p=0.002). CONCLUSIONS: Results suggest that the over-expression of p16 seen in LP play a part in the histopathology of the disease.

Transdermal estrogen gel and oral aspirin combination therapy improves fertility prognosis via the promotion of endometrial receptivity in moderate to severe intrauterine adhesion.

Intrauterine adhesion (IUA) is one of the most common gynecological diseases in women of reproductive age. IUA, particularlyin moderate to severe forms, accounts for a large percentage of infertility cases. Clinically, the first­line treatment strategy for IUA is transcervical resection of adhesion (TCRA), followed by adjuvant postoperative treatment. Estrogen is one of the classic chemotherapies used following TCRA and contributes to preventing re­adhesion following surgery. However, estrogen has limited effects in promoting pregnancy, which is the ultimate goal for IUA management. In the present study, a transdermal estrogen gel and oral aspirin combination therapy was used in patients with IUA following TCRA. Compared with in the control group (transdermal estrogen only therapy), the combination therapy significantly increased endometrial receptivity marker (αvß3 and laminin) expression in endometrium tissues. Additionally, ultrasonic examination revealed the pulsatility index and resistant index of the uterine artery were lower in the combination therapy group. Combination therapy promoted angiogenesis and prevented fibrosis following TCRA more effectively than estrogen­only therapy. Collectively, the evaluation indices, including American Fertility Society score, endometrial parameters and pregnancy rate, indicated that patients with combination therapy had better prognoses in endometrial repair and pregnancy. In conclusion, postoperative combination therapy with transdermal estrogen gel and oral aspirin may be more efficacious in enhancing endometrial receptivity by increasing uterine blood and angiogenesis, contributing to improved fertility prognosis. The findings of the present study may provide novel guidance to the clinical treatment of IUA.

Peptidomic Analysis of Female Reproductive Tract Secretion to Identify Putative Anti-Infection Peptides in the Female Genital System via Nanotechnologies.

The female genital system infections have high-incidence among various gynecological diseases. The role of endogenous peptides in female reproductive tract secretion has been rarely investigated regarding gynecological infections. To identify gynecological infections associated endogenous peptides, a comparative peptidomic profiling of vaginal secretion from sexually mature and perimenopause women was conducted in this study using nanoflow liquid chromatography-tandem mass spectrometer. A total of 3096 peptide fragments originating from 1364 precursor proteins were identified, 102 of which were discrepantly expressed, which included 60 over-expressed peptides and 42 under-expressed peptides in the sexually mature group compared with the perimenopause group. 6 differentially expressed bioactive peptides were identified to be related to immunodeficiency virus (HIV) infections, human papillomavirus (HPV) infections, bacterial vaginosis (BV) and vulvovaginal candidiasis (VVC). MUC4, MUC5A, MUC5B, MUC6, MUC17 and MUC19 peptides originating from mucin family were identified to enhance vaginal mucous immunity against infections. Moreover, with remarkable development of biomedical nanotechnology, the identified potential anti-infection peptides in our study will be useful in diagnosis and treatment of gynecological infections, especially when combined with nanoparticles. In conclusion, our findings will fill the gap on peptidomics for female genital system infections and pave the way for future studies about reproductive tract diseases management.

Towards precision medicine: discovering novel gynecological cancer biomarkers and pathways using linked data.

BACKGROUND: Next Generation Sequencing (NGS) is playing a key role in therapeutic decision making for the cancer prognosis and treatment. The NGS technologies are producing a massive amount of sequencing datasets. Often, these datasets are published from the isolated and different sequencing facilities. Consequently, the process of sharing and aggregating multisite sequencing datasets are thwarted by issues such as the need to discover relevant data from different sources, built scalable repositories, the automation of data linkage, the volume of the data, efficient querying mechanism, and information rich intuitive visualisation. RESULTS: We present an approach to link and query different sequencing datasets (TCGA, COSMIC, REACTOME, KEGG and GO) to indicate risks for four cancer types - Ovarian Serous Cystadenocarcinoma (OV), Uterine Corpus Endometrial Carcinoma (UCEC), Uterine Carcinosarcoma (UCS), Cervical Squamous Cell Carcinoma and Endocervical Adenocarcinoma (CESC) - covering the 16 healthy tissue-specific genes from Illumina Human Body Map 2.0. The differentially expressed genes from Illumina Human Body Map 2.0 are analysed together with the gene expressions reported in COSMIC and TCGA repositories leading to the discover of potential biomarkers for a tissue-specific cancer. CONCLUSION: We analyse the tissue expression of genes, copy number variation (CNV), somatic mutation, and promoter methylation to identify associated pathways and find novel biomarkers. We discovered twenty (20) mutated genes and three (3) potential pathways causing promoter changes in different gynaecological cancer types. We propose a data-interlinked platform called BIOOPENER that glues together heterogeneous cancer and biomedical repositories. The key approach is to find correspondences (or data links) among genetic, cellular and molecular features across isolated cancer datasets giving insight into cancer progression from normal to diseased tissues. The proposed BIOOPENER platform enriches mutations by filling in missing links from TCGA, COSMIC, REACTOME, KEGG and GO datasets and provides an interlinking mechanism to understand cancer progression from normal to diseased tissues with pathway components, which in turn helped to map mutations, associated phenotypes, pathways, and mechanism.

Inflammatory Myofibroblastic Tumors of the Female Genital Tract Are Under-recognized: A Low Threshold for ALK Immunohistochemistry Is Required.

Inflammatory myofibroblastic tumor (IMT) of the female genital tract is under-recognized. We investigated the prevalence of ALK-positive IMT in lesions previously diagnosed as gynecologic smooth muscle tumors. Immunohistochemistry (IHC) for ALK was performed on tissue microarrays of unselected tumors resected from 2009 to 2013. Three of 1176 (0.26%) "leiomyomas" and 1 of 44 (2.3%) "leiomyosarcomas" were ALK IHC positive, confirmed translocated by fluorescence in situ hybridization (FISH) and therefore more appropriately classified as IMT. On review significant areas of all 4 tumors closely mimicked smooth muscle tumors morphologically, but all showed at least subtle/focal features suggesting IMT. Recognizing that the distinction between IMT and leiomyoma/leiomyosarcoma can be subtle, we then reviewed 1 hematoxylin and eosin slide from each patient undergoing surgery for "leiomyoma" from 2014 to 2017 and selected cases for ALK IHC with a low threshold. Of these, 30 of 571 (5.3%) underwent IHC. Two were confirmed to be IHC positive and FISH rearranged. Of the 6 IMTs, only 1 tumor with a previous diagnosis of leiomyosarcoma, an infiltrative margin and equivocal necrosis, metastasized. Of note it demonstrated a less aggressive clinical course compared with most metastatic leiomyosarcomas (alive with disease at 6 y). The patient was subsequently offered crizotinib to which she responded rapidly. In conclusion, IMTs may closely mimic gynecologic smooth muscle tumors. IMTs account for at least 5 of 1747 (0.3%) tumors previously diagnosed as leiomyoma and 1 of 44 (2.3%) as leiomyosarcoma. These tumors may be recognized prospectively with awareness of subtle/focal histologic clues, coupled with a low threshold for ALK IHC.

GATA3 is a sensitive marker for primary genital extramammary paget disease: an immunohistochemical study of 72 cases with comparison to gross cystic disease fluid protein 15.

BACKGROUND: GATA-binding protein 3 (GATA3) has been identified as a sensitive marker for breast carcinoma but its sensitivity in primary genital extramammary Paget diseases (EMPDs) has not been well studied. METHODS: Here we investigated immunohistochemical expression of GATA3 in 72 primary genital EMPDs (35 from female, 37 from male; 45 with intraepithelial disease only, 26 with both intraepithelial disease and invasive adenocarcinoma including 14 also metastasis, 1 with metastatic adenocarcinoma only for study). We also compared GATA3 to gross cystic disease fluid protein 15 (GCDFP15) for their sensitivity. RESULTS: Positive GATA3 staining was seen in all 71 (100%) intraepithelial diseases, 25/26 (96%; female 10/10, male 15/16) invasive adenocarcinomas and 14/15 (93%; female 3/3, male 11/12) metastatic adenocarcinomas, respectively. Positive GCDFP15 staining was seen in 46/71 (65%; female 28/34 or 82%, male 18/37 or 49%) intraepithelial diseases, 20/26 (77%; female 9/10, male 11/16) invasive adenocarcinomas, and 12/15 (80%; female 2/3, male 10/12) metastatic adenocarcinomas, respectively (GATA3 versus GCDFP15: p < 0.01 for both intraepithelial disease and invasive adenocarcinoma, p = 0.28 for metastatic adenocarcinoma). In positive-stained cases, GATA3 stained more tumor cells than GCDFP15 (79% versus 25% for intraepithelial disease, 71% vs 34% for invasive adenocarcinoma, 73% vs 50% for metastatic adenocarcinoma, p < 0.01 for all 3 components). CONCLUSIONS: Our findings indicate that GATA3 is a very sensitive marker for primary genital EMPDs and is more sensitive than GCDFP15.

RNA-Binding Proteins in Female Reproductive Pathologies.

RNA-binding proteins are key regulatory molecules involved primarily in post-transcriptional gene regulation of RNAs. Post-transcriptional gene regulation is critical for adequate cellular growth and survival. Recent reports have shown key interactions between these RNA-binding proteins and other regulatory elements, such as miRNAs and long noncoding RNAs, either enhancing or diminishing their response to RNA stabilization. Many RNA-binding proteins have been reported to play a functional role in mediation of cytokines involved in inflammation and immune dysfunction, and some have been classified as global post-transcriptional regulators of inflammation. The ubiquitous expression of RNA-binding proteins in a wide variety of cell types and their unique mechanisms of degradative action provide evidence that they are involved in reproductive tract pathologies. Aberrant inflammation and immune dysfunction are major contributors to the pathogenesis and disease pathophysiology of many reproductive pathologies, including ovarian and endometrial cancers in the female reproductive tract. Herein, we discuss various RNA-binding proteins and their unique contributions to female reproductive pathologies with a focus on those mediated by aberrant inflammation and immune dysfunction.