Follicle rupture and luteinization during mammalian ovulation are informed by functionally and molecularly distinct regions of the ovarian follicle wall
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ABSTRACT:
PROVIDER: PRJNA1107203 | ENA |
REPOSITORIES: ENA
Dataset's files
| Action | DRS | |||
|---|---|---|---|---|
| SRR28877900_1.fastq.gz | Fastqsanger.gz | |||
| SRR28877900_2.fastq.gz | Fastqsanger.gz | |||
| SRR28877901_1.fastq.gz | Fastqsanger.gz | |||
| SRR28877901_2.fastq.gz | Fastqsanger.gz | |||
| SRR28877902_1.fastq.gz | Fastqsanger.gz |
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Project description:Ovulation refers to the process when the ovarian surface-facing wall of a preovulatory follicle ruptures and releases the cumulus oocyte complex (COC) into the oviduct or fallopian tube in response to hormonal cues. In parallel, the unruptured wall of the follicle within the ovary transitions to becoming a progesterone-producing corpus luteum. Ovulation is essential for fertilization and eventual pregnancy. Disruption of ovulation, whether purposefully through contraceptive intervention or idiopathically in cases of anovulatory infertility, has translational implications for human health. Importantly, key processes of ovulation, including follicle rupture and luteinization, are recapitulated in models of ex vivo ovulation despite the absence of an intact hypothalamic-pituitary-gonadal axis and intra-ovarian cues. In our study, we used an ex vivo ovulation model to identify functional and molecular differences between distinct regions of the follicle wall, which we refer to as the ruptured and unruptured sides. We observed that the unruptured side of the follicle wall exhibits hallmarks of luteinization after ovulation while the ruptured side exhibits signs of cell death. RNA-sequencing of these specific follicle regions revealed 2,099 differentially expressed genes between follicle sides without hCG exposure and 1,673 between follicle sides 12 hours post-hCG, which were further validated in vivo. We found enriched pathways that recapitulate known ovulation biology, including oxidative stress on the ruptured side and angiogenesis on the unruptured side. We also identified previously unappreciated pathways that may play an important role in ovulation, such as amino acid transport and Jag-Notch signaling on the ruptured side, as well as metal ion processing and IL-11 signaling on the unruptured side. Ultimately our studies demonstrate that our ex vivo model recapitulates known in vivo ovarian biology, identifies pathways that may be novel regulators of ovulation and luteinization, and may have future translational applications for the study of ovulatory disorders and the development of novel non-hormonal contraceptives.
2024-10-18 | GSE266449 | GEO
Project description:The rupture of ovarian follicles during ovulation is a crucial and intricate process essential for procreation, yet the molecular mechanisms behind this process are not fully understood. Here, we use high-resolution spatial transcriptomics to reveal the spatiotemporal regulation of cell-type-specific molecular programs driving follicle maturation and rupture during hormone-induced ovulation.
2023-08-21 | GSE240271 | GEO
Project description:Harmful algal blooms (HABs) arise from the rapid growth of algae in both marine and freshwater ecosystems due to the continuous global temperature rise and anthropogenic eutrophication. Humans are at a great risk of exposure to toxins released from HABs through drinking water, food, and recreational activities, making HAB toxins contaminants of emerging concern (CECs). The impact of HAB toxins on women’s reproductive health, however, remains poorly understood. Here, we investigated the effects of microcystin-LR (MC-LR), the most common HAB toxin, on the ovary, the female gonad, and associated ovarian functions. The results of a chronic daily oral mouse exposure model and an acute exposure using the mouse superovulation model revealed that MC-LR accumulated in the ovary and environmentally-relevant exposure to MC-LR perturbed follicle-stimulating hormone (FSH)-dependent follicle maturation to disrupt ovulation and luteinization. Using an ex vivo mouse follicle maturation and ovulation assay and in vitro culture of human primary granulosa cells, mechanistic studies such as the single-follicle RNA sequencing analysis and others elucidated that MC-LR inhibited protein phosphatase 1 (PP1) and interfered with PP1-mediated PI3K/AKT/FOXO1 signaling in granulosa cells, which suppressed follicle maturation, ovulation, luteinization, and progesterone secretion. Together, our study demonstrates that environmentally-relevant exposure to MC-LR acts a PP1 inhibitor to interfere with the PI3K/AKT/FOXO1 signaling in granulosa cells, which disrupts follicle maturation and results in adverse female reproductive outcomes. As a newly identified ovarian endocrine disrupting chemical (EDC), exposure to MC-LR poses a serious threat to women’s reproductive health and fertility.
2024-06-15 | GSE201806 | GEO
Project description:Gonadotropin surge acts on the preovulatory follicle of the ovary to induce luteinization of follicular cells, oocyte meiotic maturation, cumulus expansion and follicular rupture leading to ovulation. These processes are brought about by spatial and temporal changes in transcriptional regulation of genes in the follicular cells in response to the gonadotropin surge. Analysis of gene expression changes in the periovulatory follicular cells will help in delineating the signal transduction pathways involved in the above mentioned processes. In monoovulatory species like bovines, the time interval of 24-28 hours between gonadotropin surge and ovulation provides distinct advantage for studying the temporal changes in the gene expression pattern. Thus, in the present study, we attempt to identify the temporal changes in the global gene expression profile in the periovulatory follicle of buffalo cows in response to gonadotropin surge and the results suggest the involvement of Insulin-like Growth Factor 1 and cytokine signaling pathways in the periovulatory events. Keywords: Time course
2008-05-03 | GSE11312 | GEO
Project description:The process of ovulation includes oocyte meiotic maturation, follicle rupture and transformation of the follicle into a corpus luteum. These events are initiated by the midcycle surge of gonadotropins and require the coordinated regulation of thousands of genes. The aim of the study was to monitor the changes in granulosa cell gene expression across five different time points during the first 36 hours of ovulation until follicle rupture, in order to increase our understanding of the events of human ovulation. We conducted a prospective cohort study including women undergoing ovarian stimulation for fertility treatment. Women were treated in a standard antagonist protocol with individually dosed human menopausal gonadotropin (hMG) or recombinant follicle stimulating hormone (rFSH). Ovulation was induced with either recombinant hCG (rhCG) or gonadotropin releasing hormone agonist (GNRHa). The granulosa cells were collected by transvaginal ultrasound-guided follicle puncture of one follicle at two specific time points during ovulation (repeated measurements), and the study covered a total of five time points: before ovulation induction (OI), 12, 17, 32 and 36 hours after OI.
2020-03-01 | GSE133868 | GEO
Project description:Gonadotropin surge acts on the preovulatory follicle of the ovary to induce luteinization of follicular cells, oocyte meiotic maturation, cumulus expansion and follicular rupture leading to ovulation. These processes are brought about by spatial and temporal changes in transcriptional regulation of genes in the follicular cells in response to the gonadotropin surge. Analysis of gene expression changes in the periovulatory follicular cells will help in delineating the signal transduction pathways involved in the above mentioned processes. In monoovulatory species like bovines, the time interval of 24-28 hours between gonadotropin surge and ovulation provides distinct advantage for studying the temporal changes in the gene expression pattern. Thus, in the present study, we attempt to identify the temporal changes in the global gene expression profile in the periovulatory follicle of buffalo cows in response to gonadotropin surge and the results suggest the involvement of Insulin-like Growth Factor 1 and cytokine signaling pathways in the periovulatory events. Experiment Overall Design: To study the periovulatory gene expression changes in buffalo cows, an induced-ovulation model system involving sequential treatment with PGF2alpha and GnRH was standardized. The follicular wave containing at least one large follicle of ~7mm size was determined by ultrasonography on day 7 of the estrous cycle before administering exogenous PGF2alpha to induce luteolysis and follicular growth. Exogenous GnRH (100µg i.m) was administered 36h post PGF2alpha to induce LH surge. The time course of increase in LH levels post GnRH injection was monitored. Since peak LH levels are attained 2 h post GnRH administration, the time intervals of 3 h post GnRH (corresponding to1 h post LH surge) and 24 h post GnRH (corresponding to 22 h post LH surge) were chosen to identify the gene expression profile associated with immediate early and delayed changes in periovulatory follicle respectively. Thus ovaries were collected before, 1 h and 22 h post LH surge and follicle wall and granulosa cells were isolated from the ovaries and snap frozen for the purpose of RNA isolation.
2008-11-04 | E-GEOD-11312 | biostudies-arrayexpress
Project description:We previously established an alginate hydrogel-based 3D encapsulated in vitro follicle growth (eIVFG) system to culture mouse and human immature follicles in vitro. The alginate encapsulation maintained the 3D architecture of follicles and support their growth from the secondary to the antral stage to acquire maturation. Upon the stimulation of human chorionic gonadotropin (hCG), a LH analog, the grown antral follicle from eIVFG was able to rupture, undergo cumulus cell expansion, and ovulate a fertilizable metaphase II (MII) oocytes. We have also demonstrated that mouse follicles cultured using eIVFG preserved dynamic transcriptomic profile of many key genes that are essential for gonadotropin-dependent folliculogenesis, such as genes related to gonadotropin hormone receptors and ovarian steroidogenesis. However, it is unknown whether these follicles preserve molecular signatures of ovulation, which would enable this system to serve as a truly scalable and highly controllable system for nominating therapeutic and contraceptive candidates. In the present study, we treated mouse mature follicles from eIVFG with hCG to induce in vitro ovulation. Follicles were collected at 0, 1, 4, and 8 hours post-hCG for single-follicle RNA sequencing (RNA-seq) analysis. Our results showed that follicles grown from eIVFG preserve key ovulatory genes and signaling pathways.
2025-10-29 | GSE186837 | GEO
Project description:Experiments were designed to evaluate changes in the transcriptome (mRNA levels) in the ovulatory, luteinizing follicle of rhesus monkeys, using a controlled ovulation (COv) model that permits analysis of the naturally selected, dominant follicle at specific intervals (0, 12, 24, 36 hours) after exposure to an ovulatory (exogenous hCG) stimulus during the menstrual cycle. Total RNA was prepared from individual follicles (n=4-8/timepoint), with an aliquot used for microarray analysis (AffymetrixTM Rhesus Macaque Genome Array) and the remainder applied to quantitative real-time PCR (q-PCR) assays. The microarray data from individual samples distinctly clustered according to timepoints, and ovulated follicles displayed markedly different expression patterns from unruptured follicles at 36 h. Between timepoint comparisons revealed profound changes in mRNA expression profiles. The dynamic pattern of mRNA expression for steroidogenic enzymes (CYP17A, CYP19A, HSD3B2, HSD11B1, HSD11B2), StAR, and gonadotropin receptors (LHCGR, FSHR) as determined by microarray analysis correlated precisely with those from blinded q-PCR assays. Patterns of mRNA expression for EGF-like factors (AREG, EREG) and processes (HAS2, TNFAIP6) implicated in cumulus-oocyte maturation/expansion were also comparable between assays. Thus, several mRNAs displayed the expected expression pattern for purported theca (e.g., CYP17A, AREG), granulosa (CYP19A, FSHR), cumulus (HAS2, TNFAIP6) cell, and surface epithelium (HSD11B) related genes in the rodent/primate preovulatory follicle. This database will be of great value in analyzing molecular and cellular pathways associated with periovulatory events in the primate follicle (e.g. follicle rupture, luteinization, inflammatory response, and angiogenesis), and for identifying novel gene products controlling mammalian fertility. Keywords: time course Total RNA was prepared from individual follicles (n=4-8/timepoint). Dominant follicles were selected specific intervals (0, 12, 24, 36 hours) after exposure to an ovulatory (exogenous hCG) stimulus during the menstrual cycle.
2011-02-15 | E-GEOD-22776 | biostudies-arrayexpress
Project description:Ovulation is a spatiotemporally coordinated process that involves several tightly controlled events, including oocyte meiotic maturation, cumulus expansion, follicle wall rupture and repair, and ovarian stroma remodeling. To date, no studies have detailed the precise window of ovulation at single-cell resolution. Here, we performed parallel single-cell RNA-seq and spatial transcriptomics on paired mouse ovaries across an ovulation time course to map the spatiotemporal profile of ovarian cell types. We show that major ovarian cell types exhibit time-dependent transcriptional states enriched for distinct functions and have specific localization profiles within the ovary. We also identified gene markers for ovulation-dependent cell states and validated these using orthogonal methods. Finally, we performed cell-cell interaction analyses to identify ligand-receptor pairs that may drive ovulation, revealing previously unappreciated interactions. Taken together, our data provides a rich and comprehensive resource of murine ovulation that can be mined for discovery by the scientific community.
2025-04-29 | GSE294534 | GEO
Project description:The ovulatory LH surge induces rapid changes of transcriptome and cellular functions in granulosa cells (GCs) undergoing luteinization. However, it remains unclear how the changes in genome-wide gene expression are regulated. The changes of trimethylation of lysine 4 on histone H3 (H3K4me3) is associated with the rapid alteration of gene expression. In this study, we genome-widely investigated the changes of transcriptome and H3K4me3 status in mouse GCs undergoing luteinization during ovulation. GCs were obtained from mice treated with equine chorionic gonadotropin (eCG) before, 4 h and 12 h after human (h)CG injection. RNA-sequence identified a number of up- or down-regulated genes, which can be classified into six patterns according to the time-course changes of gene expression. A number of genes showed a transient up- or down-regulation at 4 h after hCG stimulation. Gene ontology analysis revealed that they were involved in the regulation of steroidogenesis, ovulation, COC expansion, angiogenesis, immune system, ROS metabolism, inflammatory response, and metabolisms. The newly identified cellular functions, DNA repair, autophagy and cell growth were found to be activated during ovulation. ChIP-sequence revealed a genome-wide and rapid change of H3K4me3 during ovulation. Integration of transcriptome and H3K4me3 data identified a number of H3K4me3-regulated genes, which were involved in the regulation of a lot of cellular functions for ovulation and luteinization. The present study demonstrated that genome-wide changes of H3K4me3 might contribute to the rapid change of genome-wide gene expression, which enables GCs acquire a lot of cellular functions within a short time for ovulation and luteinization.
2022-07-21 | GSE167938 | GEO