Electroacupuncture improves endometrial receptivity and pregnancy outcomes in controlled ovarian hyperstimulation rats by restoring Per2 circadian rhythm

Objective Controlled ovarian hyperstimulation (COH) is a critical step in in vitro fertilization-embryo transfer (IVF-ET). However, the decline in endometrial receptivity caused by COH severely restricts the success rate of implantation. Previous studies mostly focused on static molecular events, lacking a systematic exploration from the perspective of dynamic rhythms. This study aims to explore whether electroacupuncture (EA) can improve endometrial receptivity and pregnancy outcomes by repairing the disordered rhythm of the core clock gene Per2 in the endometrium caused by COH from the perspective of chronobiology. Methods A COH model was established using 126 Sprague - Dawley (SD) rats. Following EA intervention, dynamic sampling was conducted during the implantation window to assess clock gene rhythmicity, the expression of receptivity - related factors, and uterine morphological changes. Per2 −/− mice were used to preliminarily investigate whether Per2 participates in mediating the effects of EA. Results COH induced an abnormal increase in serum progesterone, leading to desynchronization of the endometrial clock gene network. Among them, the peak delay of the core clock gene Per2 was highly coupled with the abnormal peak of progesterone in time, and presented an anti - phase oscillatory pattern with the expression of the angiogenesis factor Vegf . During the implantation window, the expression of Vegf and integrin αvβ3 was down - regulated, the development of pinopodes degenerated, and the pregnancy rate was significantly reduced. EA could correct the abnormal progesterone level, repair the rhythm parameters of Per2 , up - regulate the expression of Vegf and integrin αvβ3 , improve the development of pinopodes, and significantly increase the pregnancy rate. In Per2 −/− mice, the up - regulating effect of EA on Vegf and Integrin αvβ3 was significantly weakened, preliminarily suggesting that Per2 may participate in mediating the effects of EA on endometrial receptivity. Conclusion This study provided preliminary evidence for a novel mechanism by which COH impairs endometrial receptivity from the perspective of dynamic circadian rhythm, providing experimental evidence for EA as an adjuvant intervention strategy based on circadian clock regulation in IVF-ET cycles.