Dataset Information

Lipid metabolism-related genes as biomarkers and therapeutic targets reveal endometrial receptivity and immune microenvironment in women with reproductive dysfunction.

ABSTRACT:

Background

In recent years, alterations in lipid metabolism are currently considered a hallmark feature of many diseases. However, the role in women with reproductive dysfunction (WRD) remains to be fully elucidated. Here, this study aimed to explore the effect of lipid metabolism-related genes (LMRGs) on endometrial receptivity of WRD.

Methods

This study retrospectively analyzed endometrial receptivity array (ERA) in GEO database. The differential expression genes (DEGs) were obtained by limma differential analysis, and the core genes and corresponding predicted microRNA were obtained through protein-protein interaction (PPI) analysis and TargetScan database, so as to predict the chemical targets of drug therapy. Through the intersection of DEGs and LMRGs, the target gene expression profile was obtained for subsequent consensus clustering analysis and immune analysis. In addition, the immune cell infiltration was assessed by applying the ESTIMATE and MCPcounter algorithm and potential drug targets were obtained from the HERB website.

Results

1473 genes showed differential expression between the groups of WRD and fertile women, and then a large number of lipid metabolism-related pathways and immune-related pathways were enriched. Twelve core genes and corresponding predicted miR-134-3p were obtained; most importantly, we found that these 12 genes were all LMRGs. Through drug target prediction, we obtained three drugs that regulate lipid metabolism and improve blood circulation, namely lovastatin, estrogen, and quercetin. EHHADH (AUC = 0.85) and PTEN (AUC = 0.82) have the best diagnostic performance. UMAP and heatmap revealed large differences between three clusters. LMRGs revealed specific manifestations of WRD in endometrial receptivity and immune microenvironment.

Conclusions

Our study explored the expression pattern of LMRGs in endometrium of WRD, screened the corresponding biomarkers, and proposed the combination of traditional Chinese and Western medicine to improve the endometrial receptivity.

SUBMITTER: Liu Y

PROVIDER: S-EPMC9474772 | biostudies-literature | 2022 Sep

REPOSITORIES: biostudies-literature

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Publications

Lipid metabolism-related genes as biomarkers and therapeutic targets reveal endometrial receptivity and immune microenvironment in women with reproductive dysfunction.

Liu Yang Y Yao Yanqi Y Sun Hangyu H Zhao Jiayini J Li Hongye H Wang Shanlin S Zhang Ting T Meng Meng M Zhou Shu S

Journal of assisted reproduction and genetics 20220727 9

<h4>Background</h4>In recent years, alterations in lipid metabolism are currently considered a hallmark feature of many diseases. However, the role in women with reproductive dysfunction (WRD) remains to be fully elucidated. Here, this study aimed to explore the effect of lipid metabolism-related genes (LMRGs) on endometrial receptivity of WRD.<h4>Methods</h4>This study retrospectively analyzed endometrial receptivity array (ERA) in GEO database. The differential expression genes (DEGs) were obt ...[more]

PMID: 35895215

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Project description:Background: Aquaculture of the black tiger prawn Penaeus monodon remains severely constrained by an almost total dependence on wild-caught broodstock. Reliance on wild-caught broodstock stems, for the most part, from reduced reproductive potential of captive-reared females. Reproductive performance of captive-reared females is usually characterised by longer latency period, lower egg production, egg hatch rates and post-larval survivorship compared with their wild-caught counterparts. Improved understanding of the cellular and associated molecular events occurring during peneaid ovarian maturation could therefore be fundamental to improving reproductive success of captive-reared animals. Methodology/Principle Findings: In support of other studies, our histological analyses of developing oocytes revealed differences between wild-caught and captive-reared P. monodon, including reduced lipid accumulation in oocytes of captive-reared animals. We have employed oligonucleotide microarray analysis to compare expression profiles of genes involved in ovarian maturation among wild-caught and captive-reared animals. Custom oligonucleotide microarrays were constructed and screened with transcripts derived from the ovary, cephalothorax and eyestalk from animals of all ovarian maturation stages. Ovarian maturation-related differential expression patterns were observed for 111 transcripts, with 53 transcripts displaying differential expression between wild-caught and captive-reared animals. Notably transcripts encoding vitellogenin - the major egg yolk protein precursor, and a lipid storage droplet protein (which we named pmLSD) which is involved in lipid accumulation, were found to be more highly expressed in wild-caught animals. pmLSD transcripts localise to pre-vitellogenic oocytes of wild-caught animals and the pmLSD protein is exclusively localised to the surface of lipid droplets of oocytes at vitellogenic and cortical rod stages. We have employed oligonucleotide microarray analysis to compare expression profiles of genes involved in ovarian maturation among wild-caught and captive-reared animals. Target preparation and microarray hybridisation. Ovarian RNA samples from nine wild-caught animals representing six ovarian maturation stages (P, 2, 24, V, R, E) were used in microarray hybridisations. Similarly, RNA samples from three captive-reared animals representing four maturation stages (P, 24, V, E) were used in microarray hybridisations. For wild-caught animals, samples from each ovarian maturation stage were pooled into groups of four and five, enabling two hybridisations. For captive-reared animals, samples from each ovarian maturation stage from all three animals were pooled enabling one hybridisation for each stage. Importantly, as the four stages for captive-reared animals were (1) pre-ablation pre-vitellogenic, (2) post-ablation pre-vitellogenic, (3) post-ablation vitellogenic, (4) post-ablation vitellogenic with cortical rods, this arrangement allowed for 2 samples of captive-reared pre-vitellogenic and 2 samples of captive-reared vitellogenic, thereby enabling t-tests between samples, while also allowing analysis across the whole 4 stages via cluster analysis. All hybridisations were single channel hybridisations conducted using equal amounts of RNA pooled from each individual.

Dataset Information

Lipid metabolism-related genes as biomarkers and therapeutic targets reveal endometrial receptivity and immune microenvironment in women with reproductive dysfunction.

Background

Methods

Results

Conclusions

Publications

Lipid metabolism-related genes as biomarkers and therapeutic targets reveal endometrial receptivity and immune microenvironment in women with reproductive dysfunction.

Similar Datasets

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