Lifetime ovulatory years and ovarian cancer gene expression profiles
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ABSTRACT:
ORGANISM(S): Homo sapiens
PROVIDER: GSE232352 | GEO | 2024/12/31
REPOSITORIES: GEO
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Project description:Lifetime ovulatory years and ovarian cancer gene expression profiles
| PRJNA971658 | ENA
Project description:Ovulation is triggered by the gonadotropin surge that induces the expression of two key genes, progesterone receptor (Pgr) and prostaglandin-endoperoxide synthase 2 (Ptgs2) in the granulosa cells of preovulatory follicles. Their gene products PGR and PTGS2 activate two separate pathways that are both essential for successful ovulation. Here we show that the PGR plays an additional essential role; attenuate ovulatory inflammation by diminishing the gonadotropin surge-induced Ptgs2 expression. PGR indirectly terminates Ptgs2 expression and PGE2 synthesis in granulosa cells by inhibiting the NF-κB, a transcription factor required for Ptgs2 expression. When the expression of PGR was ablated in the granulosa cells, the ovary undergoes hyperinflammatory condition manifested by excessive PGE2 synthesis, immune cell infiltration, oxidative damage, and neoplastic transformation of ovarian cells. Despite the ovary undergoes ovulations dozens or hundreds of times in one’s lifetime, the repetitive ovulatory inflammations do not leave significant tissue damage in the ovary. The PGR-driven termination of PTGS2 expression may protect ovary from the ovulatory inflammation.
2020-03-07 | GSE145107 | GEO
Project description:BackgroundGreater ovulatory years is associated with increased ovarian cancer risk. Although ovulation leads to an acute pro-inflammatory local environment, how long-term exposure to ovulation impacts ovarian carcinogenesis is not fully understood. Thus, we examined the association between gene expression profiles of ovarian tumors and lifetime ovulatory years to enhance understanding of associated biological pathways.MethodsRNA sequencing data was generated on 234 invasive ovarian cancer tumors that were high-grade serous, poorly differentiated, or high-grade endometrioid from the Nurses' Health Study (NHS), NHSII, and the New England Case Control Study. We used linear regression to identify differentially expressed genes by estimated ovulatory years, adjusted for birth decade and cohort, overall and stratified by menopausal status at diagnosis. We used false discovery rates (FDR) to account for multiple testing. Gene set enrichment analysis (GSEA) with Cancer Hallmarks, KEGG, and Reactome databases was used to identify biological pathways associated with ovulatory years.ResultsNo individual genes were significantly differentially expressed by ovulatory years (FDR > 0.19). However, GSEA identified several pathways that were significantly associated with ovulatory years, including downregulation of pathways related to inflammation and proliferation (FDR < 1.0 × 10-5). Greater ovulatory years were more strongly associated with downregulation of genes related to proliferation (e.g., E2F targets, FDR = 1.53 × 10-24; G2M checkpoints, FDR = 3.50 × 10-22) among premenopausal versus postmenopausal women at diagnosis. The association of greater ovulatory years with downregulation of genes involved in inflammatory response such as interferon gamma response pathways (FDR = 7.81 × 10-17) was stronger in postmenopausal women.ConclusionsOur results provide novel insight into the biological pathways that link ovulatory years to ovarian carcinogenesis, which may lead to development of targeted prevention strategies for ovarian cancer.
| S-EPMC9102743 | biostudies-literature
Project description:In the ovary, follicular growth and maturation are complicated processes that involve a series of morphological and physiological changes in oocytes and somatic cells leading to ovulation and luteinization, essential processes for fertility in females. Given the complexity of ovulation, characterization of genome-wide regulatory elements is essential to understand the mechanisms governing the expression of specific genes in the rapidly differentiating follicle. We therefore employed a systems biology approach to determine global transcriptional mechanisms during the early stages of the ovulatory process. We demonstrate that, following the hormonal signal that initiates ovulation, granulosa cells undergo major modification of distal regulatory elements which coincides with cistrome reprogramming of the indispensable orphan nuclear receptor, liver receptor homolog-1 (LRH-1). This cistromic reorganization correlates with the extensive changes in gene expression in ovarian granulosa cells, leading to ovulation. Together, our study yields a transcriptional map of unprecedented detail, delineating ovarian cell differentiation during the initiation of ovulation. It further demonstrates the power of complementary global approaches to accurately characterize molecular events that direct the multiple and rapid changes that characterize reproductive processes.
2019-05-14 | GSE119508 | GEO
Project description:BackgroundThe role of ovulation in epithelial ovarian cancer (EOC) is supported by the consistent protective effects of parity and oral contraceptive use. Whether these factors protect through anovulation alone remains unclear. We explored the association between lifetime ovulatory years (LOY) and EOC.MethodsLOY was calculated using 12 algorithms. Odds ratios (ORs) and 95% confidence intervals (CIs) estimated the association between LOY or LOY components and EOC among 26 204 control participants and 21 267 case patients from 25 studies. To assess whether LOY components act through ovulation suppression alone, we compared beta coefficients obtained from regression models with expected estimates assuming 1 year of ovulation suppression has the same effect regardless of source.ResultsLOY was associated with increased EOC risk (OR per year increase = 1.014, 95% CI = 1.009 to 1.020 to OR per year increase = 1.044, 95% CI = 1.041 to 1.048). Individual LOY components, except age at menarche, also associated with EOC. The estimated model coefficient for oral contraceptive use and pregnancies were 4.45 times and 12- to 15-fold greater than expected, respectively. LOY was associated with high-grade serous, low-grade serous, endometrioid, and clear cell histotypes (ORs per year increase = 1.054, 1.040, 1.065, and 1.098, respectively) but not mucinous tumors. Estimated coefficients of LOY components were close to expected estimates for high-grade serous but larger than expected for low-grade serous, endometrioid, and clear cell histotypes.ConclusionsLOY is positively associated with nonmucinous EOC. Differences between estimated and expected model coefficients for LOY components suggest factors beyond ovulation underlie the associations between LOY components and EOC in general and for non-HGSOC.
| S-EPMC10165492 | biostudies-literature
Project description:The Chinese Erhualian is one of the most prolific pig breeds in the world, which farrows at least five more piglets per litter than Western pig breeds partly due to a greater ovulation rate. Differences in the transcriptome of Chinese Erhualian and Large White ovaries directly result in variation of ovulation rate. To understand the molecular basis related to ovulation rate in Chinese indigenous and Western breeds, samples were collected and used to hybridized. This study reveals many potential avenues of investigation for seeking new insights into ovarian physiology and the genetic control of reproduction. Expression profiling experiments were conducted to identify differentially expressed genes in ovarian follicles at the preovulatory stage of a PMSG-hCG stimulated estrous cycle from 3 Chinese Erhualian and 3 Large White cycling sows by using the Affymetrix Porcine Genechip™.
2011-12-31 | E-GEOD-23985 | biostudies-arrayexpress
Project description:Leukocytes are in situ regulators for ovarian functions. However, little is known about leukocyte subpopulations and functions in ovulatory follicles, especially in humans. This study performed single-cell RNA sequencing and bioinformatics analyses using follicular aspirates obtained from four IVF patients. Nineteen clusters were identified: six follicular cells, ten subsets of leukocytes, and one RBC/platelet. Using dominant follicle tissues collected throughout the periovulatory period from normally cycling women and cultured primary human granulosa/lutein cells, we determined the cell type-specific expression of PTPRC, CD68, IL1B, and IL1R1. RNA velocity analyses revealed developmental dynamics across five granulosa cell groups and two projections of granulosa cell differentiation. To understand how leukocytes promote periovulatory changes, we sought leukocyte-derived factors potentially involved in 1) granulosa cell function by activating their receptors, 2) tissue remodeling, and 3) angiogenesis in ovulatory follicles. Collectively, these findings identified diverse leukocyte-secreted factors that facilitate ovulation and luteinization in the human ovary.
2023-01-01 | GSE206143 | GEO
Project description:The Chinese Erhualian is one of the most prolific pig breeds in the world, which farrows at least five more piglets per litter than Western pig breeds partly due to a greater ovulation rate. Differences in the transcriptome of Chinese Erhualian and Large White ovaries directly result in variation of ovulation rate. To understand the molecular basis related to ovulation rate in Chinese indigenous and Western breeds, samples were collected and used to hybridized. This study reveals many potential avenues of investigation for seeking new insights into ovarian physiology and the genetic control of reproduction.
2011-12-31 | GSE23985 | GEO
Project description:Identification of differently methylated regions of CpG islands in epithelial ovarian cancer (EOC) tissue from patients with progression free survival <3 years (worse outcome) vs. patients with PFS >3 years (good outcome, relapse free until last follow up). Patients were homogenous in regard to clinical (FIGO III/IV, serous histology, optimally resected (macroscopically tumor free), platin-taxan chemotherapy) and molecular properties (immunohistochemistry for p16, BRCA1, Ki67 and p53)).
2015-11-16 | GSE62851 | GEO
Project description:The relevance of immune-endocrine interactions to the regulation of ovarian function in teleosts is virtually unexplored. As part of the innate immune response during infection, a number of cytokines such as tumor necrosis factor α (TNFα) and other immune factors, are produced and act on the reproductive system. However, TNFα is also an important physiological player in the ovulatory process in mammals. In the present study, we have examined for the first time the effects of TNFα in vitro in preovulatory ovarian follicles of a teleost fish, the brown trout (Salmo trutta). In control and recombinant trout TNFα (rtTNFα)-treated granulosa cells, we examined the percentage of apoptosis by flow cytometry analysis and cell viability by propidium iodide (PI) staining. Furthermore, we determined the in vitro effects of rtTNFα on follicle contraction and testosterone production in preovulatory trout ovarian follicles. In addition, we analyzed the gene expression profiles of control and rtTNFα-treated ovarian tissue by microarray and real-time PCR (qPCR) analyses.Treatment with rtTNFα induces ovarian cell apoptosis, decreases granulosa cell viability and stimulates the expression of genes known to be involved in the normal ovulatory process in trout. In addition, rtTNFα causes a significant increase in follicle contraction and testosterone production. Also, using a salmonid-specific microarray platform (SFA2.0 immunochip) we observed that rtTNFα induces the expression of genes known to be involved in inflammation, proteolysis and tissue remodeling. In view of these results, we propose that TNFα could have an important role in the biomechanics of follicle weakening, ovarian rupture and oocyte expulsion during ovulation in trout, primarily through its stimulation of follicular cell apoptosis and the expression of genes involved in follicle wall proteolysis and contraction.
2010-02-23 | GSE20296 | GEO