Peripheral blood transcriptome analysis of patients with ovarian hyperstimulation syndrome through high-throughput sequencing

Abstract

Objective: Ovarian hyperstimulation syndrome (OHSS) is a frequent iatrogenic complication that arises during assisted reproduction and accounts for approximately 30% of all in vitro fertilization cycles. Using high-throughput sequencing, we investigated the peripheral blood transcriptome of patients with OHSS.Methods: Peripheral blood samples were obtained from 15 patients in each of the OHSS high-risk and low-risk groups on the ovum pick-up day. Subsequently, high-throughput sequencing was used to obtain the peripheral blood transcriptomes of five patients each from the high-and low-risk groups. Bioinformatic tools were used for mRNA expression profile mapping and screening of differentially expressed genes (DEGs). Bioinformatics techniques were also implemented in the Kyoto Encyclopedia of Genes Genomes (KEGG) signal pathway, Gene Ontology (GO) function, and protein-protein interaction (PPI) network analyses of DEGs.Results: A total of 20,031 genes were identified and 148 were found to be differentially expressed (P <0.05, |log 2 FC| > 0.58), with 52 upregulated and 96 downregulated genes. GO and KEGG analyses indicated that these genes were involved in extracellular corpuscles (GO: 0070062), plasma membrane (GO: 0005886), extracellular regions (GO: 0005576), immune system response (GO: 0006955), PI3K-Akt signaling pathways (hsa04151), cell adhesion molecules (CAMs, hsa04514), focal adhesion (hsa04510), and complement and coagulation cascades (hsa04610). The PPI network and realtime fluorescence quantitative polymerase chain reaction (qPCR) verification predicted that complement C3, von Willebrand factor, and vascular cell adhesion protein 1 proteins are highly implicated in OHSS and may serve as potential biomarkers for future OHSS studies.Conclusion: Transcriptome analysis revealed several DEGs related to OHSS risk factors in the peripheral blood, indicating that these DEGs may be novel players in OHSS development.

Vitamin D3 reduces the symptoms of ovarian hyperstimulation syndrome in mice and inhibits the release of granulosa cell angiogenic factor through pentraxin 3

“…A previous study in transgenic mice highlighted the pivotal effect of PTX3 on innate resistance to pathogens and regulation of inflammation, thus supporting its potential therapeutic role in the management of immunocompromised patients and various inflammatory conditions (Doni et al 2016 ). Peripheral blood transcriptome results in patients with OHSS and subsequent Gene Ontology and Kyoto Encyclopedia of Genes and Genomes pathway enrichment analyses revealed that differentially expressed genes in high- and low-risk patients were mainly enriched in several pathways, such as the “immune system” (Yan et al 2023 ). The above results indicated that PTX3 could be considered a therapeutic target for high-risk patients with OHSS and highlighted the potential of VD3 as a therapeutic strategy for the aforementioned patients.…”

Dose-response functional and transcriptomic effects of follicle-stimulating hormone onex vivomouse folliculogenesis

“…In addition to VEGFs, the transcriptional induction of Lhcgr, Ptgs2, and several proinflammatory cytokines (e.g., IL-1, IL-6, and TNF-α) have also been related to OHSS (78,(84)(85)(86). Proteomic data using human blood and follicular fluid showed that patients with a high risk of OHSS tended to have higher expression levels of proteins related to inflammation, complement and coagulation cascades, and cell adhesion (87,88). Consistent with these previous findings, our RNA-seq data discovered that follicles cultured with excessive FSH had significantly higher expression levels of Ptgs2, and a number of proinflammatory genes (Figure 7D), suggesting that there are other potential risks factors of OHSS induced by high doses of FSH, such as the high induction of LHCGR, PTGS2, and related PEG2 production.…”