Transgenic pig over-expressing leptin as a model for female infertility
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ABSTRACT:
PROVIDER: PRJNA994072 | ENA |
REPOSITORIES: ENA
Dataset's files
| Action | DRS | |||
|---|---|---|---|---|
| SRR25246331_1.fastq.gz | Fastqsanger.gz | |||
| SRR25246331_2.fastq.gz | Fastqsanger.gz | |||
| SRR25246332_1.fastq.gz | Fastqsanger.gz | |||
| SRR25246332_2.fastq.gz | Fastqsanger.gz | |||
| SRR25246333_1.fastq.gz | Fastqsanger.gz |
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Project description:Infertility is a growing global health concern affecting millions of couples worldwide. Both overweight and underweight individuals face reproductive issues, resulting in infertility. Due to small size and short life, mice are not necessarily suitable animal models for human infertility. While, pigs having large size, anatomical and physiological similarities with human are considered as more ideal animal model of human disease. Leptin is a well-known adipokine that serves as an endocrine signal between adiposity and fertility. However, the exact mechanisms underlying leptin's effects on reproductive function remain unclear. To shed light on this, our study focused on pigs genetically engineered to overexpress leptin. These leptin-overexpressing pigs exhibited several reproductive abnormalities, including reduced body weight and size, decreased back fat thickness, and displayed late onset of puberty, and irregular estrous behavior characterized by increased inter-estrous interval and more breeding attempts until pregnancy. This reproductive impairment in leptin pigs was followed by hormonal imbalances and altered steroidogenesis. Bulk RNA sequencing of the ovaries revealed neutrophilic infiltration followed by upregulation of inflammation related genes. To gain a deeper understanding of the cellular levels, we employed single-nucleus RNA sequencing (snRNA-seq), and found that leptin overexpression triggered immune response, suppressed follicle development and luteinization, imposing metabolism dysfunction and hormone imbalance in ovary. Further, trends of phenotypical infertility symptoms and endocrine changes in underweight female patients mirrored the alterations observed in our leptin pigs. These findings suggest that leptin-overexpressing pigs could serve as a valuable animal model for studying infertility and investigating potential therapeutic interventions.
2023-07-17 | GSE237153 | GEO
Project description:Female Infertility: Primary Ovarian Insufficiency
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Project description:Purpose: To find the difference between leptin-overexpressing and wt pig. Methods: Peripheral blood mononuclear cells (PBMCs) mRNA profiles of 6-month-old wild-type (WT) and leptin-overexpressing pig were generated by deep sequencing. Sequencing libraries were constructed according to the protocol for the Illumina TruSeq Sample preparation kit. Sequencing was performed on the Illumina X Ten sequencer. Library construction and sequencing were performed at the Genergy Biotech Co., Ltd. (Shanghai). Results: RNA-seq was performed to detect the transcriptomic changes in PBMCs in the transgenic leptin pigs. With 2-folds change and p<0.05 threshold, we found that 84 transcripts were upregulated, and 124 transcripts were downregulated in the transgenic leptin pigs. Conclusions: The leptin-overexpressing pigs exhibited remarkable resemblance to human SLE in multiple aspects of the disease.
2018-07-06 | GSE116701 | GEO
Project description:BackgroundSoluble leptin receptor (OBRe), one of several leptin receptor isoforms, is the only bona fide leptin binding protein in plasma. Our earlier studies demonstrated that OBRe modulates leptin levels in circulation. Both clinical and in vitro studies have shown that OBRe expression is inversely correlated to body weight and leptin levels. However, it is not clear whether OBRe plays an active role, either in collaboration with leptin or independently, in the maintenance of body weight.Methodology/principal findingsTo investigate the function of OBRe in the regulation of energy homeostasis, we generated transgenic mice that express OBRe under the control of human serum amyloid P (hSAP) component gene promoter. The transgene led to approximately doubling of OBRe in circulation in the transgenic mice than in wild type control mice. Transgenic mice exhibited lower body weight at 4 weeks of age, and slower rate of weight gain when compared with control mice. Furthermore, transgenic mice had lower body fat content. Indirect calorimetry revealed that transgenic mice had reduced food intake, increased basal metabolic rate, and increased lipid oxidation, which could account for the differences in body weight and body fat content. Transgenic mice also showed higher total circulating leptin, with the majority of it being in the bound form, while the amount of free leptin is comparable between transgenic and control mice.ConclusionsThese results are consistent with the role of OBRe as a leptin binding protein in regulating leptin's bioavailability and activity.
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Project description:Leptin resistance is a driving force for obesity and metabolic syndrome. Slug (Snai2 or Snail2) is an epignetic factor that may play a critical role in the development of leptin resistance in obesity. We conducted a microarray to detect molecular targets of Slug in the hypothalamus.
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Project description:In a transgenic mouse model of Alzheimer disease (AD), cleavage of the amyloid precursor protein (APP) by the α-secretase ADAM10 prevented amyloid plaque formation and alleviated cognitive deficits. Furthermore, there was a positive influence of ADAM10 over-expression on neurotransmitter-specific formation of synapses and on synaptic plasticity. To assess the influence of ADAM10 on the gene expression profile in the brain we performed microarray analysis using RNA isolated from brains of five month old mice over-expressing either the α-secretase ADAM10 or a dominant-negative mutant (dn) of this enzyme. As compared to non-transgenic wild-type mice, 355 genes were found to be differentially expressed in ADAM10 transgenic mice and 143 genes in dnADAM10 mice. A higher number of genes was found to be differentially regulated in double-transgenic mouse strains additionally expressing the human APP V717I mutant (APP[V717I]). Thus, α-secretase cleavage of over-expressed APP[V717I] alters CNS gene expression additionally. Keywords: genetic modification
2009-01-22 | GSE10908 | GEO
Project description:We employed translating ribosome affinity purification followed by RNA sequencing to isolate and analyze mRNA from the hypothalamic LepRb neurons of wild-type or leptin-deficient (Lepob/ob) mice treated with vehicle or exogenous leptin. Although the expression of most of the genes encoding the neuropeptides commonly considered to represent the main targets of leptin action were altered only following chronic leptin deprivation, our analysis revealed other transcripts that were coordinately regulated by leptin under multiple treatment conditions. Among these, acute leptin treatment increased expression of the transcription factor Atf3 in LepRb neurons.
2020-12-03 | GSE162603 | GEO