High-resolution spatial transcriptomics of hormone-induced ovulation in mice
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ABSTRACT:
ORGANISM(S): Mus musculus
PROVIDER: GSE240271 | GEO | 2023/08/21
REPOSITORIES: GEO
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Project description:Ovulation is induced by the preovulatory surge of luteinizing hormone (LH) that acts on the ovary and triggers the rupture of the preovulatory ovarian follicle by stimulating proteolysis and apoptosis in the follicle wall, causing the release of the mature oocyte. In mammals, the pro-inflammatory cytokine tumor necrosis factor α (TNFα) and prostaglandin F2α (PGF2α) are known to be involved in the control of ovulation but their role mediating the pro-ovulatory actions of LH has not been established. Here we show that Lh induces PGF2α synthesis through its stimulation of Tnfα production in trout, a primitive teleost fish. Importantly, trout recombinant Tnfα (rTnfα) and PGF2α recapitulate the stimulatory in vitro effects of salmon Lh (sLh) on contraction, proteolysis and loss of cell viability in the preovulatory follicle wall and, finally, ovulation. Furthermore, all pro-ovulatory actions of sLh are blocked by inhibition of Tnfα secretion or PG synthesis and those of rTnfα are blocked by PG synthesis inhibitors. Therefore, we provide evidence that the Tnfαâdependent increase in PGF2α production is necessary for the pro-ovulatory actions of Lh in a teleost fish. The results from this study shed light onto the mechanisms underlying the pro-ovulatory actions of LH in vertebrates and may prove important in clinical assessments of female infertility. Preovulatory follicles from brook trout from four different females (n = 4) were isolated and incubated in the absence or presence of salmon LH. Total RNA of control and LH-treated preovulatory follicles from each of the four females was analyzed.
2015-12-31 | E-GEOD-67592 | biostudies-arrayexpress
Project description:Running title: More insights into ovulation Purpose:Ovulation is the process by which mature follicles release fertilized oocytes under the stimulation of gonadotropin. This involves the precise interaction and destiny of various cells in the follicle. Granulosa cells (GCs) are the only cells that recognize and respond to ovulation LH (or HCG) signals. Therefore, the classification and deep interpretation of genes in GCs under LH surge stimulation is the key to understand ovulation. Methods: In this study, RNA-seq, Q-PCR, Western blot, gene knockout, gene knockout and other experimental techniques were used to conduct trend and classification analysis of the genes regulated by ovulation signal of LH at the cellular and individual levels. Genes that may be involved in ovulation were screened, identified and were selected for functional verification. Results:(1) Firstly, 7104 and 347 mRNA and Long noncoding RNA (LncRNA) that may be involved in ovulation activity were screened at the gene level by transcriptome sequencing technology, respectively. According to gene expression, they were divided into activated, inhibited and transient activated gene expression patterns. 44 secreted proteins, 62 transcription factors, 22 periodic expression characteristic genes, 10 ovulation process unknown genes, 16 LncRNA-target gene cis pair combinations and 41 highly expressed LncRNA were identified and listed in the three models;(2) The functions of LncRNA Gm12840 and Gm20186 were studied at the cellular level. The results showed that knockdown Gm12840/20186 not only inhibited the proliferation and hormone synthesis of GCs, but also induced cell apoptosis;(3) The function of LncRNA Gm12840 was further studied in mice, and Gm12840 knockout mice were constructed by CRISPR/CAS9 technology: Results It was found that Gm12840 knockout significantly increased the number of antral follicles and ovulation, and significantly inhibited the number of atretic follicles and antral follicles not discharged after ovulation. Gm12840 knockout significantly increased litter size at 2-3 months of age, but also significantly inhibited litter size at 7-9 months of age. Meanwhile, Gm12840 knockout also significantly inhibited the number of follicles growing in the ovary of 11-month-old mice;(4) Finally, transcriptomic sequencing analysis of wilt-type and Gm12840-/- mouse GCs showed 349 genes were differentially expressed. KEGG enrichment analysis and WB results showed that Gm12840 knockout enhanced mTOR and MAPK signals. Conclusions:The above results screened and identified genes with potential research value during ovulation process, and took LncRNA Gm12840 as an example to verify their functions at the cell and individual levels, providing reference for further revealing the ovulation process.
2024-08-27 | GSE182965 | GEO
Project description:Running title: More insights into ovulation Purpose:Ovulation is the process by which mature follicles release fertilized oocytes under the stimulation of gonadotropin. This involves the precise interaction and destiny of various cells in the follicle. Granulosa cells (GCs) are the only cells that recognize and respond to ovulation LH (or HCG) signals. Therefore, the classification and deep interpretation of genes in GCs under LH surge stimulation is the key to understand ovulation. Methods: In this study, RNA-seq, Q-PCR, Western blot, gene knockout, gene knockout and other experimental techniques were used to conduct trend and classification analysis of the genes regulated by ovulation signal of LH at the cellular and individual levels. Genes that may be involved in ovulation were screened, identified and were selected for functional verification. Results:(1) Firstly, 7104 and 347 mRNA and Long noncoding RNA (LncRNA) that may be involved in ovulation activity were screened at the gene level by transcriptome sequencing technology, respectively. According to gene expression, they were divided into activated, inhibited and transient activated gene expression patterns. 44 secreted proteins, 62 transcription factors, 22 periodic expression characteristic genes, 10 ovulation process unknown genes, 16 LncRNA-target gene cis pair combinations and 41 highly expressed LncRNA were identified and listed in the three models;(2) The functions of LncRNA Gm12840 and Gm20186 were studied at the cellular level. The results showed that knockdown Gm12840/20186 not only inhibited the proliferation and hormone synthesis of GCs, but also induced cell apoptosis;(3) The function of LncRNA Gm12840 was further studied in mice, and Gm12840 knockout mice were constructed by CRISPR/CAS9 technology: Results It was found that Gm12840 knockout significantly increased the number of antral follicles and ovulation, and significantly inhibited the number of atretic follicles and antral follicles not discharged after ovulation. Gm12840 knockout significantly increased litter size at 2-3 months of age, but also significantly inhibited litter size at 7-9 months of age. Meanwhile, Gm12840 knockout also significantly inhibited the number of follicles growing in the ovary of 11-month-old mice;(4) Finally, transcriptomic sequencing analysis of wilt-type and Gm12840-/- mouse GCs showed 349 genes were differentially expressed. KEGG enrichment analysis and WB results showed that Gm12840 knockout enhanced mTOR and MAPK signals. Conclusions:The above results screened and identified genes with potential research value during ovulation process, and took LncRNA Gm12840 as an example to verify their functions at the cell and individual levels, providing reference for further revealing the ovulation process.
2024-08-27 | GSE182964 | GEO
Project description:Vitrification is a method for long-term biological sample cryopreservation without causing intra- and extra-cellular ice formation. We recently established a novel closed vitrification system to cryopreserve mouse ovarian follicles. Using the 3D alginate hydrogel encapsulated in vitro follicle growth (eIVFG) method, we have demonstrated that compared to freshly-harvested follicles, vitrified follicles have normal follicle and oocyte reproductive outcomes. Our recent study further demonstrated the faithful preservation of molecular signatures of follicle-stimulating hormone (FSH)-stimulated follicle maturation in vitrified follicles. However, it is unknown whether ovulation, another crucial gonadotropin-dependent follicular event, and involved ovulatory gene regulatory pathways are well conserved in vitrified follicles. Fresh and vitrified follicles grown for 8 days by eIVFG were collected at 0, 1, 4 and 8-hour post human chorionic gonadotropin (hCG) treatment for the single-follicle RNA sequencing. Principal component analysis (PCA) and Pearson’s correlation analysis revealed that vitrified follicles have similar transcriptomic profiles to fresh follicles. Furthermore, the expression of several genes essential for ovulation were comparable between vitrified and fresh follicles. In summary, these results demonstrate that our closed vitrification system preserves follicular transcriptomic dynamics during ex vivo ovulation. Together with our previous findings that vitrification preserves FSH-stimulated follicle maturation, the integration of vitrification of immature follicles and eIVFG has a great potential to serve as an additional fertilization preservation approach for young cancer patients and endangerers species. Moreover, follicle vitrification enables a high-content ovarian follicle biobank, which can greatly improve the throughput of eIVFG for studying ovulation biology, anovulatory disease, toxicology, and novel contraceptive drug development targeting ovulation.
2023-09-20 | GSE227091 | 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:Previous studies have shown that PR is a critical regulator of ovulation. The PR-null mice (PRKO) failed to ovulate due to a failure in the rupture of the preovulatory follicles.
2012-10-04 | GSE37354 | GEO
Project description:Ovulation is induced by the preovulatory surge of luteinizing hormone (LH) that acts on the ovary and triggers the rupture of the preovulatory ovarian follicle by stimulating proteolysis and apoptosis in the follicle wall, causing the release of the mature oocyte. In mammals, the pro-inflammatory cytokine tumor necrosis factor α (TNFα) and prostaglandin F2α (PGF2α) are known to be involved in the control of ovulation but their role mediating the pro-ovulatory actions of LH has not been established. Here we show that Lh induces PGF2α synthesis through its stimulation of Tnfα production in trout, a primitive teleost fish. Importantly, trout recombinant Tnfα (rTnfα) and PGF2α recapitulate the stimulatory in vitro effects of salmon Lh (sLh) on contraction, proteolysis and loss of cell viability in the preovulatory follicle wall and, finally, ovulation. Furthermore, all pro-ovulatory actions of sLh are blocked by inhibition of Tnfα secretion or PG synthesis and those of rTnfα are blocked by PG synthesis inhibitors. Therefore, we provide evidence that the Tnfα–dependent increase in PGF2α production is necessary for the pro-ovulatory actions of Lh in a teleost fish. The results from this study shed light onto the mechanisms underlying the pro-ovulatory actions of LH in vertebrates and may prove important in clinical assessments of female infertility.
2015-12-31 | GSE67592 | GEO
Project description:Whole saliva is contains major, minor and gingival crevicular fluid/secretions and it plays vital role in maintaining the oral health, three pair of major salivary glands consist of parotid, submandibular and sub-lingual glands. Saliva is a good biological fluid to explore health and disease status of human. Further, the saliva secrets from major salivary glands and have various biomolecules such as, proteins, enzymes and ions originated from serum and saliva is easily accessible through a safe and noninvasive method. In contrast, the concentrations of biomolecules in saliva are generally one tenth to one thousand of the levels in blood. Ovulation is an exclusive process through the mature (pre-ovulatory) ovarian follicles reacts to the surge of luteinizing hormone (LH) and burst to discharge fertilizable oocytes. The LH surge initiates a flow of proteolytic actions with the aim of control ovulation. Presently, many salivary proteins are have been showed as a biomarker such as Sjogren’s syndrome, Lung cancer, oral and Systemic diseases, HIV-seropositive patients, dental pellicle development, and hyperglycemia. However, there is no prominent marker protein was reported for monitoring ovulation process in human saliva. It is important prediction of fertile period in women for various applications like assisted reproduction and invitro fertilization.
2016-12-22 | PXD000921 | Pride
Project description:Ovulation requires sequential molecular events and structural remodeling in the ovarian follicle for the successful release of a mature oocyte capable of being fertilised. Critical to this process is progesterone receptor (PGR), a transcription factor highly yet transiently expressed in granulosa cells of preovulatory follicles. Progesterone receptor knockout (PRKO) mice are anovulatory, with a specific and complete defect in follicle rupture. Therefore, this model was used to examine the critical molecular and biochemical mechanisms necessary for successful ovulation. We used microarrays to identify putative PGR-regulated genes in granulosa cells at a time when PGR expression is maximal (eCG + 8h hCG) and the preovulatory follicle is undergoing the final changes necessary for successful ovulation.
2018-04-20 | GSE92437 | GEO
Project description:Previous studies have shown that PR is a critical regulator of ovulation. The PR-null mice (PRKO) failed to ovulate due to a failure in the rupture of the preovulatory follicles. To experimentally induce ovulation, the wild type and PR null mice (C57BL/6, 24–28 d old) were injected ip with 5 IU of PMSG and 48 h later by 5 IU of hCG. Ovaries were collected at 11 h and total RNA was analyzed using Affymetrix mouse arrays
2012-10-04 | E-GEOD-37354 | biostudies-arrayexpress