Implication of vasopressin receptor genes (AVPR1A and AVPR1B) in the susceptibility to polycystic ovary syndrome
Polycystic ovary syndrome (PCOS) is a complex heterogenous disorder manifesting with various reproductive, endocrine, and metabolic derangements such as insulin resistance and hyperglycemia. The arginine vasopressin peptide (AVP), also called or antidiuretic hormone (ADH), modulates metabolic functions such as glucose hemostasis, insulin sensitivity, and lipid metabolism via binding to two central and peripheral receptors (AVPR1A and AVPR1B). In the present study, we aimed to detect whether the AVPR1A and AVPR1B genes confer risk for PCOS.
A novel ITGB8 transcript variant sustains ovarian cancer cell survival through genomic instability and altered ploidy on a mutant p53 background
Transcript variants and protein isoforms are central to unique tissue functions and maintenance of homeostasis, in addition to being associated with aberrant states such as cancer, where their crosstalk with the mutated tumor suppressor p53 may contribute to genomic instability and chromosomal rearrangements. We previously identified several novel splice variants in ovarian cancer RNA-sequencing datasets; herein, we aimed to elucidate the biological effects of the Integrin Subunit Beta 8 variant (termed pITGB8-205).
Causal relationship between inflammatory cytokines and polycystic ovary syndrome: a bidirectional mendelian randomization study
Polycystic ovary syndrome (PCOS) is defined as a chronic low-grade inflammatory reproductive endocrine disorder. PCOS can induce various metabolic disorders, which are associated with a state of mild and slow-acting inflammation. Nevertheless, the causal relationship between polycystic ovary syndrome and inflammatory factors is uncertain. The causality between inflammatory cytokines and PCOS was analyzed by bidirectional Mendelian randomization (MR) in this current probe. We performed an interactive MR study to assess the causal relationships between 91 inflammatory cytokines and PCOS using Genome Wide Association Study (GWAS) data. We underwent dual-sample MR analysis with inverse variance weights (IVW) as the predominant MR methodology with multiple validity and heterogeneity analyses. MR-Egger, weighted median, simple mode, weighted mode and MR-PRESSO were analyzed as multiple likelihood sensitivity analyses to enhance the final results.The results came out interleukin-1-alpha (IL-1 A) levels (odds ratio [OR] = 1.051, 95% fiducial interval [95% CI] = 1.009-1.095, P = 0.02) and oncostatin-M (OSM) levels ( [OR] = 1.041, [95% CI] = 1.001-1.082, P = 0.04) were positively associated with the development of PCOS. Moreover, interleukin-7 (IL-7) levels ([OR] = 0.935, [95% CI] = 0.884-0.989, P = 0.02); interleukin-15 receptor subunit alpha (IL15RA) levels ([OR] = 0.959, [95% CI] = 0.929-0.99, P = 0.01); and C-X-C motif chemokine 11 (CXCL11) levels ([OR] = 0.959, [95% CI] = 0.922-0.996. P = 0.03) were strongly negatively associated with PCOS. However, we did not find any strong positive results in the reverse analysis, suggesting that although inflammatory factors contribute to the pathogenesis of PCOS, PCOS itself does not trigger inflammatory factor production.Our study provides genetic evidence for the connection between systemic inflammatory regulators and PCOS. Treatments targeting specific inflammatory factors may help to mitigate the risk of PCOS. The levels of five of the 91 inflammatory factors included in this study, namely, IL1A and OSM, were associated with PCOS. IL1A and OSM contribute to the progression of PCOS while IL-7, IL15RA, and CXCL11 levels are negatively correlated with the development of PCOS.
SOX17 expression in ovarian clear cell carcinoma
Recent studies have revealed that the Sry-related HMG box gene 17 (SOX17) plays an important role in ovarian carcinogenesis. Unlike other types of ovarian cancer, ovarian clear cell carcinoma (OCCC) has a distinct pathobiological phenotype, often harboring an AT-rich interaction domain 1 A (ARID1A) mutation. In the present study, to determine the SOX17 in OCCC cells, we immunohistochemically examined SOX17 expression in 47 whole-tissue specimens of OCCC. Although not statistically significant, SOX17-high immunoreactivity tended to be related to unfavorable patient outcomes. We also aimed to determine the relationship of SOX17 with ARID1A. Double immunofluorescence staining demonstrated that SOX17 immunoreactivity was not associated with ARID1A immunoreactivity. Immunoblotting revealed that SOX17 was abundantly expressed in cultured OVISE and RMG-V OCCC cells, but not in OVTOKO OCCC cells. Polyubiquitinated bands of SOX17 were observed in MG132 treated OVTOKO, but not in OVISE or RMG-V OCCC cells. Notably, si-RNA-mediated knockdown of a deubiquitinase enzyme, ubiquitin C-terminal hydrolase L1, increased polyubiquitination followed by proteasome degradation of SOX17 in OVISE. These findings indicate that SOX17 is not uniformly and heterogeneously expressed in OCCCs, independent of ARID1A deficiency. Impaired ubiquitin-mediated proteasome degradation may stabilize SOX17 in some OCCC cells.
Machine learning models in evaluating the malignancy risk of ovarian tumors: a comparative study
The study aimed to compare the diagnostic efficacy of the machine learning models with expert subjective assessment (SA) in assessing the malignancy risk of ovarian tumors using transvaginal ultrasound (TVUS).
A simple and practical approach to elective egg freezing to control costs and expand access to care
Social elective egg freezing (EEF) is now widely used globally but in many countries is unaffordable to many women because of high costs and lacking insurance coverage. Efforts to reduce costs, therefore, are of importance. Surprisingly, a simple, well-defined and practical approach ensuring optimal outcomes for EEF has, however, so-far not been published. We, therefore, conducted a narrative review of the literature for relevant articles regarding the different steps of ovarian stimulation (OS) in the EEF process, in order to define such a standard protocol. This review revealed that in order to maximize oocyte yields with minimal number of OS cycles - while ensuring patient safety - a multiple-dose GnRH antagonist protocol with a daily gonadotropin dose of 300 IU appears best, unless patients demonstrate a polycystic ovarian phenotype, suggestive of likely high responses. The initial gonadotropin should be recFSH, while LH supplementation should be co-administered with the addition of GnRH antagonist. Final follicular maturation should be triggered by GnRH agonist trigger, with a dual trigger (1000-1500 IU hCG) considered for suboptimal responders to GnRH agonist trigger, optionally with Cabergoline to mitigate ovarian hyperstimulation syndrome (OHSS) in high responders.
Characterization of the gut microbiota in patients with SARS-CoV-2 infection during controlled ovarian stimulation
The Coronavirus disease 2019 (COVID-19) pandemic has emerged as a global health crisis, with clinical manifestations including those suggesting injury to various organs such as the ovaries, which implies that it extends beyond respiratory infections. Changes in gut microbiota may exhibit correlations with the mechanisms and stages of severity in COVID-19, as well as a link with sex hormones, embryo development, and pregnancy. Controlled ovarian stimulation (COS) is used to induce the development of multiple high-quality follicles during in vitro fertilization (IVF). Our research aimed to investigate whether patients infected with COVID-19 have altered gut microbiota compositions that would affect the outcomes of COS.
Human umbilical cord mesenchymal stem cell-derived extracellular vesicles harboring IGF-1 improve ovarian function of mice with premature ovarian insufficiency through the Nrf2/HO-1 pathway
Premature ovarian insufficiency (POI) is a disease with medical, psychological and reproductive implications, but its common therapies have limited efficacy and a likelihood of complications. This study delves into the therapeutic role of human umbilical cord mesenchymal stem cell-derived extracellular vesicles (hUC-MSCs-EVs) in POI mice through the insulin-like growth factor 1 (IGF-1)/nuclear factor E2 related factor 2 (Nrf2)/heme oxygenase-1 (HO-1)/autophagy pathway.
Follicular fluid-derived extracellular vesicles miR-34a-5p regulates granulosa cell glycolysis in polycystic ovary syndrome by targeting LDHA
Polycystic ovary syndrome (PCOS) is highly prevalent in women of reproductive age worldwide, exhibits highly heterogeneous clinical presentation and biochemical parameters, and has no cure. This study aimed to investigate the role of miR-34a-5p in PCOS, its effect on glycolysis in granulosa cells (GCs), and its potential contribution to follicular dysregulation.
Targeting mitochondrial metabolism with CPI-613 in chemoresistant ovarian tumors
There is evidence indicating that chemoresistance in tumor cells is mediated by the reconfiguration of the tricarboxylic acid cycle, leading to heightened mitochondrial activity and oxidative phosphorylation (OXPHOS). Previously, we have shown that ovarian cancer cells that are resistant to chemotherapy display increased OXPHOS, mitochondrial function, and metabolic flexibility. To exploit this weakness in chemoresistant ovarian cancer cells, we examined the effectiveness of the mitochondrial inhibitor CPI-613 in treating preclinical ovarian cancer.
Near-infrared fluorescent molecular probes with cetuximab in the in vivo fluorescence imaging for epithelial ovarian cancer
Near-infrared fluorescence (NIRF) imaging is an excellent choice for image-guided surgery due to its simple operation and non-invasiveness. Developing tumor-specific fluorescent molecular probes is key to fluorescence imaging-guided surgery. EGFR (epidermal growth factor receptor) is closely related to the proliferation and growth of tumor cells and is highly expressed in epithelial ovarian cancer (EOC). The study aims to construct a NIR fluorescent molecular probe using cetuximab (an EGFR monoclonal antibody) and investigate its feasibility for targeting EOC in vivo through fluorescence imaging.
Correction: Transcriptomics of cumulus cells - a window into oocyte maturation in humans
The dietary phytochemical index and its relation to polycystic ovary syndrome: a case-control study
Polycystic ovary syndrome (PCOS), a hormonal disorder affecting women of reproductive age, can be significantly impacted by diet. This study explores the relationship between a diet rich in phytochemicals, measured by the Dietary Phytochemical Index (DPI), and PCOS, along with associated health markers.
Chiglitazar ameliorates dehydroepiandrosterone-induced polycystic ovary syndrome in rats
Polycystic ovary syndrome (PCOS) is an endocrine and metabolic disorder accompanied by ovulatory dysfunction. Insulin resistance (IR) is a key pathogenic mechanism in PCOS, and insulin sensitizers, such as metformin and pioglitazone, can improve PCOS symptoms. Chiglitazar, a pan-peroxisome proliferator-activated receptor (pan-PPAR) agonist, is also an insulin sensitizer; however, its therapeutic effects have not yet been studied in PCOS. We evaluated the therapeutic effects of chiglitazar in a rat model of PCOS.
Progesterone peak influences embryonic developmental morphokinetics on trigger day? A retrospective study
Premature Progesterone Rise (PPR) is characterized by elevated serum progesterone concentrations either towards the end of the follicular phase or on the trigger day, surpassing a pre-defined threshold value. Aim of the study is to evaluate the impact of PPR exceeding 1.5 ng/ml at the time of hCG-trigger on embryo morphokinetic parameters and to identify predictive biomarkers of in IntraCytoplasmic Sperm Injection (ICSI) cycles outcomes.
Exploring lncRNA expression in follicular fluid exosomes of patients with obesity and polycystic ovary syndrome based on high-throughput sequencing technology
Infertility is a reproductive health problem that attracts worldwide attention. Polycystic ovary syndrome (PCOS) is a major cause of female infertility and patients with obesity and PCOS are particularly common in clinical practice. Long non-coding RNA (lncRNAs) are a functional core in cells that regulate gene expression, transcription, and chromatin modification processes, and participate in epigenetics, cell cycle, and cell differentiation. LncRNAs are assumed to play a role in the occurrence and development of PCOS; however, their specific mechanism of action remains to be elucidated.
ATF3 mediates PM2.5-induced apoptosis and inflammation in ovarian granulosa cells
Particulate matter 2.5 (PM2.5) pollution has emerged as a major global public health concern because of its adverse effects on human health. Our group has previously demonstrated that PM2.5 exposure can seriously impair ovarian function. However, the underlying mechanisms remain a mystery. This study verifies ovarian damage in mice, evidenced by inflammatory cell infiltration and follicular atresia, following 5 months of PM2.5 exposure via tracheal drip (35 µg/m³ for low dose and 150 µg/m³ for high dose). In addition, PM2.5 exposure inhibited the cell viability of human granulosa cells (KGN) and induced apoptosis at the concentrations of 50, 100, and 150 µg/mL for 24 h. The apoptosis of KGN cells induced by inflammation contributes to follicular atresia. Furthermore, we conducted RNA-sequencing analysis to identify the genes and pathways triggered by PM2.5 (100 µg/mL) exposure, which decreases the KGN cell viability. We found a significant increase in Activating Transcription Factor 3 (ATF3). Further mechanistic studies reveal a strong association between PM2.5-induced apoptosis, inflammation, and ATF3 with its downstream oxidative stress signals. In summary, the ATF3 pathway serves a vital role in the ovarian injury caused by PM2.5 exposures.
MSCs-derived EVs protect against chemotherapy-induced ovarian toxicity: role of PI3K/AKT/mTOR axis
Chemotherapy detrimentally impacts fertility via depletion of follicular reserves in the ovaries leading to ovarian failure (OF) and development of estrogen deficiency-related complications. The currently proposed options to preserve fertility such as Oocyte or ovarian cortex cryopreservation are faced with many technical obstacles that limit their effective implementation. Therefore, developing new modalities to protect ovarian function remains a pending target. Exosomes are nano-sized cell-derived extracellular vesicles (EVs) with documented efficacy in the field of regenerative medicine. The current study sought to determine the potential beneficial effects of mesenchymal stem cells (MSCs)-derived EVs in experimentally induced OF. Female albino rats were randomly allocated to four groups: control, OF group, OF + MSCs-EVs group, OF + Rapamycin (mTOR inhibitor) group, and OF + Quercetin (PI3K/AKT inhibitor) group. Follicular development was assessed via histopathological and immunohistochemical examination, and ovarian function was evaluated by hormonal assay. PI3K/Akt/mTOR signaling pathway as a key modulator of ovarian follicular activation was also assessed. MSCs-EVs administration to OF rats resulted in restored serum hormonal levels, preserved primordial follicles and oocytes, suppressed ovarian PI3K/AKT axis and downstream effectors (mTOR and FOXO3), modulated miRNA that target this axis, decreased expression of ovarian apoptotic markers (BAX, BCl2) and increased expression of proliferation marker Ki67. The present study validated the effectiveness of MSCs-EVs therapy in preventing ovarian insufficiency induced by chemotherapy. Concomitant MSCs-EVs treatment during chemotherapy could significantly preserve ovarian function and fertility by suppressing the PI3K/Akt axis, preventing follicular overactivation, maintaining normal ovarian cellular proliferation, and inhibiting granulosa cell apoptosis.
Correction: Correlation between ovarian follicular development and Hippo pathway in polycystic ovary syndrome
Relationship between smoking, excessive androgen and negative emotions in women with polycystic ovary syndrome (PCOS)
Lifestyle intervention is the first-line treatment for PCOS. Numerous studies have investigated the effect of various lifestyle factors, including dietary habit, smoking, and alcohol consumption on PCOS women. These studies have found that such factors may be associated with physiological parameters such as androgen, and emotional states like anxiety or depression. Smoking, a harmful lifestyle habit widely recognized to contribute to various diseases, has also been found to be related to PCOS. Current research has not adequately compared the effects of smoking with other lifestyle habits on PCOS, and there is little mention of its relationship with the emotional states of patients with PCOS. To further elucidate the association between smoking and other lifestyle factors with clinical symptoms in patients with PCOS, we conducted a cross-sectional evaluation using data from Peking University Third Hospital, with a special focus on analyzing smoking habits and comparing it with a variety of lifestyle factors.
Astaxanthin improves assisted reproductive technology outcomes in poor ovarian responders through alleviating oxidative stress, inflammation, and apoptosis: a randomized clinical trial
Poor ovarian response (POR) to controlled ovarian stimulation (COS) remains challenging, especially in advanced-age women with diminished ovarian reserve, resulting in low live birth rates. Many patients prefer to conceive with their eggs, underscoring the need for improved treatments. This study explores astaxanthin potential as a COS adjuvant to improve ovarian response and assisted reproductive technology (ART) outcomes, considering its impact on oxidative stress (OS), inflammation, and apoptosis, which are key factors in POR.