Conclusion
Aberrant expression of endometrial PER2 might contribute to impaired endometrial receptivity and development of RIF via regulating SHTN1, KLF5, and STEAP4.
Methods
The study was initially an in silico study, with confirmatory lab-based data from primary human endometrial stromal cells (hESCs) as well as endometrial biopsies obtained from 60 women undergoing gynecological surgery in a clinical research center. The study included 30 RIF women and 30 age-matched and body mass index-matched controls.
Objective
We aimed to assess the core circadian clock gene profiling in human endometrium across the menstrual cycle and the possible gene interaction networks in the endometrial receptivity of window of implantation (WOI) as well as RIF.
Results
Initial data mining and bioinformatics analysis of human endometrial microarray datasets across the menstrual cycle and between RIF women versus controls demonstrated the varied expression of core circadian clock genes across menstrual cycle, including the key role of PER2 in WOI and RIF. A PER2-centered network was investigated in the regulation of endometrial receptivity. We also confirmed the evidently increased mRNA expression of SHTN1, RXFP1, KLF5, and STEAP4 in the endometrium of RIF women, displaying the same trend as PER2 did, without any changes in MT1E and FKBP5. Treatment of PER2 siRNA in hESCs verified the positive regulation of PER2 to SHTN1, KLF5, and STEAP4.