Alterations in gonadotropin, apoptotic and metabolic pathways in granulosa cells warrant superior fertility of the Dummerstorf high fertility mouse line 1 (FL1)
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ABSTRACT:
PROVIDER: PRJNA862938 | ENA |
REPOSITORIES: ENA
Dataset's files
| Action | DRS | |||
|---|---|---|---|---|
| SRR20676800.fastq.gz | Fastqsanger.gz | |||
| SRR20676781.fastq.gz | Fastqsanger.gz | |||
| SRR20676782.fastq.gz | Fastqsanger.gz | |||
| SRR20676783.fastq.gz | Fastqsanger.gz | |||
| SRR20676784.fastq.gz | Fastqsanger.gz |
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Project description:During the last decades, several mouse models provided insights into the regulation of folliculogenesis. In contrast to the commonly used transgenic or knockout mouse models, the Dummerstorf high-fertility mouse line 1 is a worldwide unique selection experiment for increased female reproductive performance and high fertility. These mice are characterized by various alterations on endocrine and molecular levels, which have the potential to improve folliculogenesis and therefore lead to increased ovulation rates. To get insights into the cellular mechanisms leading to the high fertility phenotype we used granulosa cells isolated from antral follicles for mRNA sequencing and measured hormones and growth factors associated with follicular development. Our results indicate that the crosstalk between different intracellular signaling pathways in the granulosa cells are improved, follicular atresia in FL1 might be decreased due to enhanced granulosa cell survival and by improving the efficiency of intracellular signaling, glucose metabolism and signal transduction, FL1 mice have several advantages in reproductive performance and therefore increased the ovulation rate without health issues.
2023-02-08 | GSE209918 | GEO
Project description:The development and maturation of ovarian follicles is a complex and highly regulated process, which is essential for successful ovulation. During recent decades, several mouse models provided insights into the regulation of folliculogenesis. In contrast to the commonly used transgenic or knockout mouse models, the Dummerstorf high-fertility mouse line 1 (FL1) is a worldwide unique selection experiment for increased female reproductive performance and extraordinary high fertility. Interactions of cycle-related alterations of parameters of the hypothalamic pituitary gonadal axis and molecular factors in the ovary lead to improved follicular development and therefore increased ovulation rates in FL1 mice. FL1 females almost doubled the number of ovulated oocytes compared to the unselected control mouse line. To gain insights into the cellular mechanisms leading to the high fertility phenotype we used granulosa cells isolated from antral follicles for mRNA sequencing. Based on the results of the transcriptome analysis we additionally measured hormones and growth factors associated with follicular development to complement the picture of how the signaling pathways are regulated. While IGF1 levels are decreased in FL1 mice in estrus, we found no differences in insulin, prolactin and oxytocin levels in FL1 mice compared to the control line. The results of the mRNA sequencing approach revealed that the actions of insulin, prolactin and oxytocin are restricted local to the granulosa cells, since hormonal receptor expression is differentially regulated in FL1 mice. Additionally, numerous genes, which are involved in important gonadotropin, apoptotic and metabolic signaling pathways in granulosa cells, are differentially regulated in granulosa cells of FL1 mice.We showed that an overlap of different signaling pathways reflects the crosstalk between gonadotropin and growth factor signaling pathways, follicular atresia in FL1 mice is decreased due to improved granulosa cell survival and by improving the efficiency of intracellular signaling, glucose metabolism and signal transduction, FL1 mice have several advantages in reproductive performance and therefore increased the ovulation rate. Therefore, this worldwide unique high fertility model can provide new insights into different factors leading to improved follicular development and has the potential to improve our understanding of high fertility.
| S-EPMC9898973 | biostudies-literature
Project description:The objective of the present study was to identify genes that are involved in increasing the ovulation number in mouse line FL1 that had been selected for high fertility performance. Keywords: Comparative gene expression profiling
2008-09-22 | GSE11113 | 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:Inhibin α knockout (Inha-/-) female mice develop sex cord-stromal ovarian cancer with complete penetrance and previous studies demonstrate that the pituitary gonadotropins [follicle stimulating hormone (FSH) and luteinizing hormone (LH)] are influential modifiers of granulosa cell tumor development and progression in inhibin-deficient females. Recent studies have demonstrated that Inha-/- ovarian follicles develop precociously to the early antral stage in prepubertal mice without any increase in serum FSH and these studies suggested that in the absence of inhibins, granulosa cells differentiate abnormally, and thus at sexual maturity may undergo an abnormal response to gonadotropin signaling. To test this hypothesis, we stimulated immature WT and Inha-/- female mice prior to gross tumor formation with gonadotropin analogs, and subsequently examined post-gonadotropin induced ovarian follicle development, as well as preovulatory and hCG-induced gene expression changes in granulosa cells. We find that at three weeks of age, inhibin-deficient ovaries do not show further antral development nor undergo cumulus expansion. Widespread alterations in the transcriptome of gonadotropin-treated Inha-/- granulosa cells suggest that gonadotropins initiate an improper program of cell differentiation in Inha-/- cells. Overall, our experiments reveal that inhibins are essential for the normal gonadotropin-dependent response of granulosa cells. (2) Genotypes (WT, Inh KO) collected from 2 preovulatory granulosa cells with and without hCG, in triplicate independent samples
2011-02-01 | E-GEOD-20466 | biostudies-arrayexpress
Project description:Inhibin α knockout (Inha-/-) female mice develop sex cord-stromal ovarian cancer with complete penetrance and previous studies demonstrate that the pituitary gonadotropins [follicle stimulating hormone (FSH) and luteinizing hormone (LH)] are influential modifiers of granulosa cell tumor development and progression in inhibin-deficient females. Recent studies have demonstrated that Inha-/- ovarian follicles develop precociously to the early antral stage in prepubertal mice without any increase in serum FSH and these studies suggested that in the absence of inhibins, granulosa cells differentiate abnormally, and thus at sexual maturity may undergo an abnormal response to gonadotropin signaling. To test this hypothesis, we stimulated immature WT and Inha-/- female mice prior to gross tumor formation with gonadotropin analogs, and subsequently examined post-gonadotropin induced ovarian follicle development, as well as preovulatory and hCG-induced gene expression changes in granulosa cells. We find that at three weeks of age, inhibin-deficient ovaries do not show further antral development nor undergo cumulus expansion. Widespread alterations in the transcriptome of gonadotropin-treated Inha-/- granulosa cells suggest that gonadotropins initiate an improper program of cell differentiation in Inha-/- cells. Overall, our experiments reveal that inhibins are essential for the normal gonadotropin-dependent response of granulosa cells.
2011-02-01 | GSE20466 | 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:The objective of the present study was to identify genes that are involved in increasing the ovulation number in mouse line FL1 that had been selected for high fertility performance. Experiment Overall Design: Ovaries from 30 animals of line FL1 and of the control line DUKsi were collected at the metestrous stage, combined to 6 pools each, and processed for microarray analysis.
2008-10-25 | E-GEOD-11113 | biostudies-arrayexpress
Project description:Single-cell RNA-seq (10x) of the goat ovarian granulosa cells samples from high fertility group (>three babys per birth) and low fertility group (< two babys per birth). The goal of this project is to explore the role of ovarian granulosa cells on the fertility of goat at single cell level. We would like to investigate the role of ovarian granulosa cells on the ovulation rate which indicates fertility. Therefore the ovarian granulosa cells from different population (hihg or low fertility groups animals) were analyzed.
2021-12-01 | GSE135688 | GEO
Project description:The goal of this study was designe to search for the granulosa cells contribution on fertility. Single-cell RNA-seq of the goat ovarian granulosa cells samples from high fertility group (>three babys per birth) and low fertility group (< two babys per birth). And each group was divided into three subgroup based in the size of follicles: large, medium, and small follicles.
2020-08-01 | GSE135897 | GEO