Adiponectin receptor 1 regulates endometrial receptivity via the adenosine monophosphate-activated protein kinase/E-cadherin pathway

Endometrial receptivity is essential for successful embryo implantation and pregnancy initiation and is regulated via various signaling pathways. Adiponectin, an important adipokine, may be a potential regulator of reproductive system functions. The aim of the present study was to elucidate the regulatory role of adiponectin receptor 1 (ADIPOR1) in endometrial receptivity. The endometrial receptivity between RL95-2 and AN3CA cell lines was confirmed using an in vitro JAr spheroid attachment model. 293T cells were transfected with control or short hairpin (sh)ADIPOR1 vectors and RL95-2 cells were transduced with lentiviral particles targeting ADIPOR1. Reverse transcription-quantitative PCR and immunoblot assays were also performed. ADIPOR1 was consistently upregulated in the endometrium during the mid-secretory phase compared with that in the proliferative phase and in receptive RL95-2 cells compared with that in non-receptive AN3CA cells. Stable cell lines with diminished ADIPOR1 expression caused by shRNA showed reduced E-cadherin expression and attenuated in vitro endometrial receptivity. ADIPOR1 regulated AMP-activated protein kinase (AMPK) activity in endometrial epithelial cells. Regulation of AMPK activity via dorsomorphin and 5-aminoimidazole-4-carboxamide ribonucleotide affected E-cadherin expression and in vitro endometrial receptivity. The ADIPOR1/AMPK/E-cadherin axis is vital to endometrial receptivity. These findings can help improve fertility treatments and outcomes.