Whole-transcriptome sequencing reveals the effects of acupuncture on early embryos post-IVF-ET in poor ovarian response.

BACKGROUND

Poor ovarian response (POR) refers to a pathological condition where the ovaries respond inadequately to gonadotropin stimulation during ovulation induction. The decline in both the quantity and quality of available oocytes makes achieving pregnancy through IVF-ET more challenging. Several studies have demonstrated that acupuncture can improve embryo quality, increase the number of high-quality embryos, and enhance pregnancy outcomes in IVF-ET patients, although the underlying mechanisms remain unclear. Therefore, this study aimed to investigate the molecular mechanisms by which acupuncture influences early embryo development in POR mice after IVF-ET through whole-transcriptome sequencing.

METHODS

We established POR mice model and performed acupuncture treatment. Fresh denuded oocytes were retrieved and transplanted via IVF-ET into new donor female mice to obtain early-stage embryo tissues. Vaginal smear tests were conducted to monitor estrous cycle changes, while oocyte retrieval, ovarian wet weight, and ovarian index were assessed. Serum concentrations of anti-Müllerian hormone (AMH), follicle-stimulating hormone (FSH), estradiol (E2), and luteinizing hormone (LH) were measured via ELISA. Histopathological changes and apoptosis in the ovaries were evaluated using HE and TUNEL staining. Whole-transcriptome sequencing was employed to establish expression profiles of differentially expressed mRNAs (DEmRNAs), DEmiRNAs, DElncRNAs, and DEcircRNAs. The circ/lncRNA-miRNA-mRNA network was constructed to analyze the biological functions and potential mechanisms of acupuncture on early embryo development post-IVF-ET in POR mice.

RESULTS

Our results demonstrated that acupuncture improved ovarian function in POR mice, corrected serum hormone imbalances, and alleviated abnormal apoptosis in ovarian granulosa cells. Through whole-transcriptome sequencing, we identified 685 DEmRNAs, 13 DEmiRNAs, 325 DElncRNAs, and 4 DEcircRNAs exhibiting regulatory trends. By constructing the circ/lncRNA-miRNA-mRNA network, we found that miR-291a-3p, miR-294-3p, and miR-295-3p may serve as key targets influencing early embryo development via multiple pathways, including the Toll-like receptor signaling pathway and p53 signaling pathway.

CONCLUSION

Overall, our study is the first to reveal the molecular mechanisms by which acupuncture improves early embryo development under POR conditions, providing new evidence for the use of acupuncture in assisted reproduction.