Transciptional profile analysis of the gonadal (peri-uterine) white adipose tissue of pregnant mice
Ontology highlight
ABSTRACT:
PROVIDER: PRJNA481062 | ENA |
REPOSITORIES: ENA
Dataset's files
| Action | DRS | |||
|---|---|---|---|---|
| SRR7521720.fastq.gz | Fastqsanger.gz | |||
| SRR7521711.fastq.gz | Fastqsanger.gz | |||
| SRR7521721.fastq.gz | Fastqsanger.gz | |||
| SRR7521712.fastq.gz | Fastqsanger.gz | |||
| SRR7521722.fastq.gz | Fastqsanger.gz |
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Project description:In this study we performed RNA sequencing to determine the transcriptome of the gonadal white adipose tissue of pregnant wild type mice. We further assessed, using conditional RankΔFoxn1 knockout mice (which lack expression of Rank in the thymic epithelia), how the expression of the receptor Rank in the thymic medullary epithelia affects the transcriptional program of this tissue during pregnancy, and whether adoptive transfer of natural regulatory Tregs can rescue the alterations observed in the RankΔFoxn1 dams. For this study, we isolated at day E17.5 of pregnancy, the gonadal (peri-uterine) white adipose tissue of wildtype RankWt as well as of RankΔFoxn1 dams pregnant females that were treated at days E0.5-2.5 of pregnancy with either vehicle (PBS) or with 1x105 sorted-purified wild-type natural Tregs isolated from RankWt pregnant E7.5-8.5 donors (denoted as RankΔFoxn1_Treg). For the isolation of viable Tregs for the transplant, we generated RankWt dams that express GFP from the Foxp3 promoter (by crossing to reporter mice), and use the expression of GFP to mark and isolate bona fide Tregs and, in addition, Neuropilin1 to denote the thymic origin of the Tregs. Of note, RankWt as well as of RankΔFoxn1 dams mice also carried the GFP-Foxp3 transgene and where treated with vehicle solution (PBS) at day E0.5-2.5. Total RNA was extracted from the isolated gonadal white adipose tissue of the three described cohorts (RankWt_veh, RankΔFoxn1_veh, and RankΔFoxn1_Treg) and analyzed by Quant-seq. Our study shows how the presence of Rank receptors in the thymic epithelium, functioning via natural Tregs, regulate the inflammatory and metabolic pathways implicated in adipose tissue biology during pregnancy.
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Project description:Embryo implantation is a complex process which involves biochemical and physiological interactions between an implantation-competent blastocyst and a receptive uterus. However, the exact biochemical changes of uterine fluid, uterus, and plasma during peri-implantation remain unclear. This study aims to characterize the biochemical and metabolic changes that occur during the peri-implantation period of early pregnancy, using mice as an animal model. Gas chromatography-mass spectrometry was used to analyze the metabolite profiles of the uterus, uterine fluid, and maternal plasma at pre-implantation and implantation. The multivariate analyses, ANOVA and Tukey's HSD test, were applied to detect significant changes in metabolites and metabolic pathways. The metabolic networks were reconstructed in silico based on the identified metabolites and KEGG metabolic framework. Between pre-implantation day 1 and day 4, dramatic metabolic changes were observed in the uterine fluid that could be important for blastocyst development and protection against the harsh uterine environment. Palmitoleic acid, fumaric acid, and glutaric acid changed levels at day 4 in the uterus, suggesting that they may be associated with endometrial receptivity. Both the uterus and maternal plasma showed profound changes in cellular metabolism at the early implantation period, including upregulation of branched-chain amino acids and intermediates of one-carbon metabolism, an upregulation of glyoxylate and dicarboxylate metabolism, and downregulation of aerobic respiration; all of which could be involved in the regulation of the maternal-fetal interface, alternative nutrient utilization, and energy preservation for implantation as well as later placentation and fetal development to ensure successful embryo implantation.
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Project description:Purpose: characterize the uterine transcriptome profiles of pregnant (P) versus non-pregnant (NP) cows during early pregnancy and attempted to define a potential set of marker genes that can be valuable for predicting pregnancy outcome. Methods: beef cows were synchronized and artificially inseminated at detected estrus. Six days after AI, jugular blood samples and a biopsy from the uterine horn contralateral to the ovary containing the corpus luteum were collected. Based on pregnancy outcome on day 30, samples were retrospectively allocated to the following groups: Pregnant and Non-Pregnant. Both groups had similar plasma progesterone concentrations on D6. Uterine biopsies were submitted to RNA-Seq analysis in a Illumina HiScanSQ platform. Results: The 272,685,768 million filtered reads were mapped to the Bos taurus reference genome and 14,654 genes were analyzed for differential expression between groups. Transcriptome data showed that 216 genes are differently expressed when comparing NP versus P uterine tissue (Padj≤0.1). More specifically, 36 genes were up-regulated in P cows and 180 are up-regulated in NP cows. Conclusions: this study characterized a unique set of genes, expressed in the uterus on 6 days after insemination, that indicate a receptive state leading to pregnancy success. Furthermore, expression of such genes can be used as potential markers to efficiently predict pregnancy success.
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