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Reproduction, Fertility, and Development Jun 2024Context Altered signalling of androgens, anti-Müllerian hormone or transforming growth factor beta (TGFβ) during foetal development have been implicated in the...
Expression of transforming growth factor β signalling molecules and their correlations with genes in loci linked to polycystic ovary syndrome in human foetal and adult tissues.
Context Altered signalling of androgens, anti-Müllerian hormone or transforming growth factor beta (TGFβ) during foetal development have been implicated in the predisposition to polycystic ovary syndrome (PCOS) in later life, aside from its genetic predisposition. In foetal ovarian fibroblasts, TGFβ1 has been shown to regulate androgen signalling and seven genes located in loci associated with PCOS. Since PCOS exhibits a myriad of symptoms, it likely involves many different organs. Aims To identify the relationships between TGFβ signalling molecules and PCOS candidate genes in different tissues associated with PCOS. Methods Using RNA sequencing data, we examined the expression patterns of TGFβ signalling molecules in the human ovary, testis, heart, liver, kidney, brain tissue, and cerebellum from 4 to 20weeks of gestation and postnatally. We also examined the correlations between gene expression of TGFβ signalling molecules and PCOS candidate genes. Key results TGFβ signalling molecules were dynamically expressed in most tissues prenatally and/or postnatally. FBN3 , a PCOS candidate gene involved in TGFβ signalling, was expressed during foetal development in all tissues. The PCOS candidate genes HMGA2, YAP1 , and RAD50 correlated significantly (P TGFBR1 in six out of the seven tissues examined. Conclusions This study suggests that possible crosstalk occurs between genes in loci associated with PCOS and TGFβ signalling molecules in multiple tissues, particularly during foetal development. Implications Thus, alteration in TGFβ signalling during foetal development could affect many tissues contributing to the multiple phenotypes of PCOS in later life.
Topics: Humans; Female; Polycystic Ovary Syndrome; Signal Transduction; Transforming Growth Factor beta; Adult; Ovary; Fetus; Male; Pregnancy; Gene Expression Regulation, Developmental; Testis; Fibrillins
PubMed: 38894494
DOI: 10.1071/RD23174 -
Diagnostics (Basel, Switzerland) Jun 2024Struma ovarii is a rare type of ovarian teratoma primarily composed of over 50% thyroid tissue. Its occurrence is reported in 2-5% of all ovarian teratomas, with... (Review)
Review
Struma ovarii is a rare type of ovarian teratoma primarily composed of over 50% thyroid tissue. Its occurrence is reported in 2-5% of all ovarian teratomas, with approximately 0.5% to 10% showing malignant transformation. Managing it during pregnancy poses significant challenges as pregnancy can promote the growth of malignant struma ovarii due to elevated levels of ovarian and pregnancy-related hormones, including estrogen, progesterone, and human chorionic gonadotrophin (hCG). Most ovarian tumors, including struma ovarii, are detected during routine ultrasonography in the first and second trimesters, often as acute emergencies. Diagnosis during pregnancy is rare, with some cases incidentally discovered during cesarean section when inspecting the adnexa for ovarian cysts. This review explores the diagnostic, management, and therapeutic approaches to struma ovarii during pregnancy.
PubMed: 38893698
DOI: 10.3390/diagnostics14111172 -
Diagnostics (Basel, Switzerland) May 2024Endometriosis-associated ovarian cancer (EAOC) is a well-known type of cancer that arises from ovarian endometrioma (OE). OE contains iron-rich fluid in its cysts due to...
BACKGROUND
Endometriosis-associated ovarian cancer (EAOC) is a well-known type of cancer that arises from ovarian endometrioma (OE). OE contains iron-rich fluid in its cysts due to repeated hemorrhages in the ovaries. However, distinguishing between benign and malignant tumors can be challenging. We conducted a retrospective study on magnetic resonance (MR) relaxometry of cyst fluid to distinguish EAOC from OE and reported that this method showed good accuracy. The purpose of this study is to evaluate the accuracy of a non-invasive method in re-evaluating pre-surgical diagnosis of malignancy by a prospective multicenter cohort study.
METHODS
After the standard diagnosis process, the R2 values were obtained using a 3T system. Data on the patients were then collected through the Case Report Form (CRF). Between December 2018 and March 2023, six hospitals enrolled 109 patients. Out of these, 81 patients met the criteria required for the study.
RESULTS
The R2 values calculated using MR relaxometry showed good discriminating ability with a cut-off of 15.74 (sensitivity 80.6%, specificity 75.0%, AUC = 0.750, < 0.001) when considering atypical or borderline tumors as EAOC. When atypical and borderline cases were grouped as OE, EAOC could be distinguished with a cut-off of 16.87 (sensitivity 87.0%, specificity 61.1%).
CONCLUSIONS
MR relaxometry has proven to be an effective tool for discriminating EAOC from OE. Regular use of this method is expected to provide significant insights for clinical practice.
PubMed: 38893596
DOI: 10.3390/diagnostics14111069 -
Science Signaling Jun 2024Suppression of GLP-1 release by a gut microbiota-derived metabolite induces polycystic ovary syndrome.
Suppression of GLP-1 release by a gut microbiota-derived metabolite induces polycystic ovary syndrome.
Topics: Polycystic Ovary Syndrome; Female; Humans; Gastrointestinal Microbiome; Glucagon-Like Peptide 1; Animals
PubMed: 38889225
DOI: 10.1126/scisignal.adr0297 -
The Journal of International Medical... Jun 2024Pelvic masses frequently originate from the pelvic cavity and are often associated with uterine, ovarian, or intestinal disorders. This report describes the case of a... (Review)
Review
Pelvic masses frequently originate from the pelvic cavity and are often associated with uterine, ovarian, or intestinal disorders. This report describes the case of a patient with a pelvic mass diagnosed as a retroperitoneal dermoid cyst at our hospital. We analyzed this case and conducted a literature review, to mitigate the risk of misdiagnosis and enhance the treatment of retroperitoneal masses.
Topics: Humans; Female; Dermoid Cyst; Retroperitoneal Neoplasms; Uterine Neoplasms; Adenomyoma; Tomography, X-Ray Computed; Adult
PubMed: 38886867
DOI: 10.1177/03000605241255810 -
International Journal of Surgery... Jun 2024Immune cells play a pivotal role in maintaining ovarian function. However, the specific contributions of different immune cell phenotypes to the pathogenesis of specific...
BACKGROUND
Immune cells play a pivotal role in maintaining ovarian function. However, the specific contributions of different immune cell phenotypes to the pathogenesis of specific ovarian-related diseases remain poorly understood. We aim to investigate the correlation between 731 immunophenotypes and ovarian-related diseases.
MATERIALS AND METHODS
Utilizing publicly available genetic data, we undertook a series of quality control measures to identify instrumental variables (IVs) associated with exposure. Subsequently, we conducted two-sample Mendelian randomization (MR) using inverse variance weighting to explore the causal relationships between 731 immune cell features and six ovarian-related diseases: ovarian cysts, ovarian dysfunction, premature ovarian failure (POF), polycystic ovary syndrome (PCOS), benign neoplasm of ovary, and malignant neoplasm of ovary at the genetic level. Sensitivity analyses, including leave-one-out and other MR analysis models, were performed. Finally, Bayesian colocalization (COLOC) analysis was employed to identify specific co-localized genes, thereby validating the MR results.
RESULTS
At the significance level corrected by Bonferroni, four immune phenotypes, including CD25 on IgD- CD38- B cells, were associated with ovarian cysts; four immune phenotypes, including CD39+ CD4+ T cell Absolute Count, were associated with ovarian dysfunction; eight immune phenotypes, including SSC-A on HLA DR+ CD8+ T cells, were associated with POF; five immune phenotypes, including CD20- CD38- B cell Absolute Count, were associated with PCOS; five immune phenotypes, including CD4+ CD8dim T cell Absolute Count, were associated with benign ovarian tumors; and three immune phenotypes, including BAFF-R on IgD- CD38+ B cells, were associated with malignant ovarian tumors. Sensitivity analysis indicated robust results. COLOC analysis identified four immune cell co-localized variants (rs150386792, rs117936291, rs75926368, rs575687159) with ovarian diseases.
CONCLUSION
Our study elucidates the close genetic associations between immune cells and six ovarian-related diseases, thereby providing valuable insights for future research endeavors and clinical applications.
PubMed: 38884272
DOI: 10.1097/JS9.0000000000001814 -
MMW Fortschritte Der Medizin Jun 2024
Review
Topics: Humans; Female; Pelvic Pain; Diagnosis, Differential; Acute Pain
PubMed: 38871911
DOI: 10.1007/s15006-024-3855-x -
Annales D'endocrinologie Jun 2024Primary diseases of adipose tissue are rare disorders resulting from impairments in the physiological functions of adipose tissue (lipid stockage and endocrine... (Review)
Review
Primary diseases of adipose tissue are rare disorders resulting from impairments in the physiological functions of adipose tissue (lipid stockage and endocrine function). It mainly refers to lipodystrophy syndromes with subcutaneous adipose tissue atrophy and/or altered body distribution of adipose tissue leading to insulin resistance, diabetes, hepatic steatosis, dyslipidemia, cardiovascular complications and polycystic ovary syndrome in women. Those syndromes are congenital or acquired, and lipoatrophy is partial or generalized. The diagnosis of lipodystrophy syndromes is often unrecognized, delayed and/or inaccurate, while it is of major importance to adapt investigations to search for specific comorbidities, in particular cardiovascular involvement, and set up multidisciplinary care, and in some cases specific treatment. Physicians have to recognize the clinical and biological elements allowing to establish the diagnosis. Lipodystrophic syndromes should be considered, notably, in patients with diabetes at a young age, with a normal or low BMI, negative pancreatic autoantibodies, presenting clinical signs of lipodystrophy and insulin resistance (acanthosis nigricans, hyperandrogenism, hepatic steatosis, high insulin doses). The association of diabetes and a family history of severe and/or early cardiovascular disease (coronary atherosclerosis, cardiomyopathy with rhythm and/or conduction disorders) may reveal Dunnigan syndrome, the most frequent form of familial lipodystrophy, due to LMNA pathogenic variants. Clinical assessment is primarily done through clinical examination: acanthosis nigricans, abnormal adipose tissue distribution, lipoatrophy, muscular hypertrophy, acromegaloid or Cushingoid features, lipomas, highly visible subcutaneous veins, may be revealing signs. The amount of circulating adipokines may reflect of adipose dysfunction with low leptinemia and adiponectinemia. Other biological metabolic parameters (hypertriglyceridemia, hyperinsulinemia, increased glycemia and hepatic enzymes) may also represent markers of insulin resistance. Quantification of total body fat by impedancemetry or dual-photon X-ray absorptiometry (DEXA) reveals decreased total body mass, in correlation with adipose tissue atrophy; metabolic magnetic resonance imaging can also quantify intraperitoneal and abdominal fat and the degree of hepatic steatosis. Histological analysis of adipose tissue showing structural abnormalities should be reserved for clinical research. Acquired lipodystrophic syndromes most often lead to similar clinical phenotype as congenital syndromes with generalized or partial lipoatrophy. The most frequent causes are old anti-HIV therapy or glucocorticoid treatments. Family history, history of treatments and clinical examination, including a careful physical examination, are keys for diagnosis.
Topics: Humans; Lipodystrophy; Adipose Tissue; Female; Insulin Resistance; Polycystic Ovary Syndrome
PubMed: 38871502
DOI: 10.1016/j.ando.2024.05.019 -
Science (New York, N.Y.) Jun 2024Antimalarial suppresses ovarian androgen synthesis to relieve polycystic ovary syndrome.
Antimalarial suppresses ovarian androgen synthesis to relieve polycystic ovary syndrome.
Topics: Animals; Female; Humans; Mice; Androgens; Antimalarials; Ovary; Polycystic Ovary Syndrome
PubMed: 38870311
DOI: 10.1126/science.adq0328 -
Science (New York, N.Y.) Jun 2024Polycystic ovary syndrome (PCOS), a prevalent reproductive disorder in women of reproductive age, features androgen excess, ovulatory dysfunction, and polycystic...
Polycystic ovary syndrome (PCOS), a prevalent reproductive disorder in women of reproductive age, features androgen excess, ovulatory dysfunction, and polycystic ovaries. Despite its high prevalence, specific pharmacologic intervention for PCOS is challenging. In this study, we identified artemisinins as anti-PCOS agents. Our finding demonstrated the efficacy of artemisinin derivatives in alleviating PCOS symptoms in both rodent models and human patients, curbing hyperandrogenemia through suppression of ovarian androgen synthesis. Artemisinins promoted cytochrome P450 family 11 subfamily A member 1 (CYP11A1) protein degradation to block androgen overproduction. Mechanistically, artemisinins directly targeted lon peptidase 1 (LONP1), enhanced LONP1-CYP11A1 interaction, and facilitated LONP1-catalyzed CYP11A1 degradation. Overexpression of LONP1 replicated the androgen-lowering effect of artemisinins. Our data suggest that artemisinin application is a promising approach for treating PCOS and highlight the crucial role of the LONP1-CYP11A1 interaction in controlling hyperandrogenism and PCOS occurrence.
Topics: Animals; Female; Humans; Mice; Rats; Androgens; Artemisinins; Cholesterol Side-Chain Cleavage Enzyme; Disease Models, Animal; Hyperandrogenism; Mitochondrial Proteins; Ovary; Polycystic Ovary Syndrome; Proteolysis; Mice, Inbred C57BL; Young Adult; Adult; Rats, Sprague-Dawley; ATP-Dependent Proteases
PubMed: 38870290
DOI: 10.1126/science.adk5382