AQP2 is regulated by estradiol in human endometrium and is associated with spheroid attachment in vitro.

17β‑estradiol (E2) and aquaporin 2 (AQP2) are associated with endometrial receptivity, and E2 directly regulates AQP2 expression in endometrial cancer cells. The present study aimed to investigate the role of AQP2 in embryo implantation. Normal endometrial samples were collected at the Women's Hospital (Hangzhou, China) from women seeking in vitro fertilization and embryo transfer; women with endometrial abnormalities were excluded from the study. Samples were categorized into early‑mid proliferative, late proliferative, early secretory, mid‑secretory and late secretory phase groups, according to the menstrual cycle. The mRNA and protein expression levels of AQP2 were assessed in normal human endometrium in response to E2 via reverse transcription‑quantitative polymerase chain reaction and western blotting, respectively. The effects of AQP2 on spheroid attachment were assessed using an in vitro co‑culture assay with small interfering (si)RNA against AQP2. The highest expression levels of AQP2 were observed in the late proliferative and mid‑secretory phases, with the lowest levels detected in the early proliferative and late secretory phases. In addition, treatment with 10‑9 or 10‑7 M E2 for 24 h upregulated AQP2 in the cultured endometrium. Knockdown of AQP2 by siRNA significantly decreased JAr spheroid attachment; however, this effect was significantly reversed when AQP2 siRNA‑transfected cells were treated with 10‑7 M E2. The results of the present study suggested that AQP2 expression levels in human endometrium may be mediated by estrogen, and low AQP2 expression levels may be a potential cause of impaired uterine receptivity.