Mus musculus
Ontology highlight
ABSTRACT:
PROVIDER: PRJNA1087375 | ENA |
REPOSITORIES: ENA
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Project description:Purpose: profiling the differential transcripts usage in wild type and Plxnd1 knockout condition of brain Methods: transcriptome analysis by the RNA-seq through the mRNA pull-down Results: We performed RNA-seq analysis from neonatal mouse striatum and found that the repulsive Semaphorin 3E (Sema3E)-Plexin-D1 guidance signaling transcriptionally upregulates Mtss1 in striatonigral projecting neurons of basal ganglia circuitry Conclusions: our findings demonstrate a molecular mechanism in which repulsive guidance cues activate an autoregulatory program enabling growing axons to perform both avoiding repellants and continuing axonal extension in the navigation to their target
2022-12-31 | GSE196558 | GEO
Project description:A surge of luteinizing hormone (LH) from the pituitary gland triggers ovulation, oocyte maturation, and luteinization for successful reproduction in mammals. Since the signaling molecules RAS and ERK1/2 are activated by a LH surge in granulosa cells of preovulatory follicles, we disrupted Erk1/2 in mouse granulosa cells and provide in vivo evidence that these kinases are necessary for LH-induced oocyte resumption of meiosis, ovulation, and luteinization. In addition, biochemical analyses and selected disruption of the Cebpb gene in granulosa cells demonstrate that C/EBP is a critical downstream mediator of ERK1/2 activation. These mouse models provide in vivo systems in which to define the context specific and molecular mechanisms by which granulosa cells respond to LH and these mechanisms are relevant to the regulation of human fertility and infertility. Immature wild type or ERK1/2 conditonal knock-out mice were injected with 5IU equine chorionic gonadotropin (eCG)-48h followed by 5 IU hCG injection. The ovarian granulosa cells were collected at hCG 0h, 2.5h, or 4h and the gene expression pforiles were compared by microarray method.
2009-03-20 | E-GEOD-15315 | biostudies-arrayexpress
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: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:Striatal medium spiny neurons (MSN) are critically involved in motor control, and their degeneration is a principal component of Huntington’s disease. We find that the transcription factor Ctip2 (also known as Bcl11b) is central to MSN differentiation and striatal development. Within the striatum, it is expressed by all MSN, while it is excluded from essentially all striatal interneurons. In the absence of Ctip2, MSN do not fully differentiate, as demonstrated by dramatically reduced expression of a large number of MSN markers, including DARPP-32, FOXP1, Chrm4, Reelin, MOR1, GluR1, and Plexin-D1. Furthermore, MSN fail to aggregate into patches, resulting in severely disrupted patch-matrix organization within the striatum. Finally, heterotopic cellular aggregates invade the Ctip2-/- striatum suggesting a failure by MSN to repel these cells in the absence of Ctip2. In order to investigate the molecular mechanisms that underlie Ctip2-dependent differentiation of MSN and that underlie the patch-matrix disorganization in the mutant striatum, we directly compared gene expression between wild type and mutant striatum at P0. Because CTIP2-expressing MSN constitute 90-95% of the neurons within the striatum, we reasoned that we should be able to detect changes in medium spiny neuron gene expression in Ctip2 null mutants. We microdissected out small regions of striatum at matched locations in wild type and Ctip2-/- mutant littermates at P0 and investigated gene expression with Affymetrix microarrays. We selected the 153 most significant genes and further analyzed them to identify a smaller set of genes of potentially high biological relevance. In order to verify the microarray data and define the distribution of the identified genes in the striatum, we performed in situ hybridization or immunohistochemistry for 12 selected genes: Plexin-D1, Ngef, Nectin-3, Kcnip2, Pcp4L1, Neto1, Basonuclin 2, Fidgetin, Semaphorin 3e, Secretagogin, Unc5d, and Neurotensin. We find that all these genes are either specifically downregulated (Plexin-D1, Ngef, Nectin-3 Kcnip2, Pcp4L1, Neto1), or upregulated (Basonuclin 2, Fidgetin, Semaphorin 3e, Secretagogin, Unc5d, Neurotensin), in the Ctip2-/- striatum, confirming and extending the microarray results. Together, these data indicate that Ctip2 is a critical regulator of MSN differentiation, striatal patch development, and the establishment of the cellular architecture of the striatum. Keywords: mutant analysis
2007-12-15 | GSE9330 | GEO
Project description:A surge of luteinizing hormone (LH) from the pituitary gland triggers ovulation, oocyte maturation, and luteinization for successful reproduction in mammals. Since the signaling molecules RAS and ERK1/2 are activated by a LH surge in granulosa cells of preovulatory follicles, we disrupted Erk1/2 in mouse granulosa cells and provide in vivo evidence that these kinases are necessary for LH-induced oocyte resumption of meiosis, ovulation, and luteinization. In addition, biochemical analyses and selected disruption of the Cebpb gene in granulosa cells demonstrate that C/EBP is a critical downstream mediator of ERK1/2 activation. These mouse models provide in vivo systems in which to define the context specific and molecular mechanisms by which granulosa cells respond to LH and these mechanisms are relevant to the regulation of human fertility and infertility.
2009-03-20 | GSE15315 | 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 | GSE167939 | 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
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: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