Integration Analysis of Metabolome and Transcriptome Reveals the Effect of Lipopolysaccharide on Ovary Response to Stimulation

ABSTRACT Objective This study aimed to elucidate the underlying mechanisms by which lipopolysaccharide (LPS) influences differential ovarian responses to controlled ovarian stimulation at the metabolite and gene levels. Materials and Methods A total of 16 female mice were randomly allocated into LPS and control group. Each mice underwent controlled ovarian stimulation. Oocytes were gathered and quantified. Ovarian tissue samples from 8 mice and blood samples from 16 mice were collected. Metabolomics analysis was conducted for both ovary tissues and blood samples. Transcriptome sequencing analysis was used for ovary tissues. Spearman's correlation analysis was performed to identify the metabolites and their corresponding differential transcripts genes within the key signaling pathway. Results The number (86 vs. 122) and rate (49.7% vs. 78.2%) of metaphase II (MII) oocytes were markedly lower in LPS group (p < 0.001). Compared with control group, metabolites related to carbohydrates and lipid were decreased in ovary tissue of LPS group while metabolites related to amino acid and fatty acid beta‐oxidation were decreased in serum of LPS group. Within the category of biological processes, terms associated with the regulation of lipid metabolic process and steroid metabolic, biosynthetic process were downregulated in the LPS group. Correlation analysis indicated five genes (Lcn2, S100a9, S100a8, Muc5b, Muc5ac) in IL‐17 signaling pathway were positively related to the catabolites of polyunsaturated fatty acids and negatively related to dihydroxyacetone phosphate. Conclusions This study provided evidence that inflammation has damaging effect on ovary response to controlled ovarian stimulation, linked to dysfunctions in lipid, carbohydrate, and amino acid metabolism. IL‐17 signal pathways may play a critical role in this process.