The molecular mechanism of naringin improving endometrial receptivity of OHSS rats

Abstract Controlling ovarian hyperstimulation syndrome (OHSS) in the controlled ovarian hyperstimulation treatment is necessary to increase the implantation success rate. This study aimed to explore the effect of naringin on the endometrial receptivity of OHSS rats. Female rats were randomly assigned to six groups: Blank, model, low‐dose naringin (100 mg/kg/day), medium‐dose naringin (200 mg/kg/day), high‐dose naringin (400 mg/kg/day), and positive (0.18 mg/kg/day estradiol valerate) groups. Except for the blank group, rats established the OHSS model on Day 7, and their treatments were from Day 0 to 14, separately. Hematoxylin and eosin, immunohistochemical, and scanning electron microscopy were performed to detect the naringin effects on the endometrial receptivity of the OHSS model. Next, circRNAs transcriptome analysis was performed to screen circRNAs. Western blot analysis and real‐time quantitative PCR were used to verify it. Our study showed that naringin treatments increased embryo number, endometrial thickness, pinopodes number, and Ki67 expression in the OHSS rats. Moreover, the result of circRNAs transcriptome sequencing showed that naringin significantly inhibited the rnocirc_008140 expression in the OHSS rats and significantly inhibited the changes of 28 gene ontology terms and three Kyoto Encyclopedia of Genes and Genomes pathways which were induced by OHSS. Abcc4 and Rps6ka5 genes were the enriched genes of those pathways. Finally, 24 miRNA target genes of rnocirc_008140 were predicted. Our study showed that naringin significantly improved the endometrial receptivity of OHSS rats to increase the embryo implantation success by reducing rnocirc_008140‐adsorbed miRNAs to regulate Abcc4 and Rps6ka5 expression.