Progesterone Upregulated the Expression of AQP1 and AQP5 in the Mice Uterine Myometrium to Delay Preterm Birth via β-Catenin Signaling Pathway.

Progesterone has been widely used to prevent preterm birth (PTB), and its specific therapeutic mechanism is still unclear. Myometrium aquaporins (AQPs) were associated with PTB. This study aimed to investigate the effect of progesterone on PTB and its underlying molecular mechanisms related to myometrium AQPs (AQP1, AQP5). We used lipopolysaccharide (LPS) to stimulate pregnant mice and human uterine smooth muscle cells (HUSMCs), thereby establishing a PTB model. Immunohistochemistry and immunocytochemistry revealed localizations of AQP1 and AQP5 in mice myometrium and HUSMCs, respectively. Western blots were used to detect AQP1, AQP5, iNOS, and COX2 expression in HUSMCs and mice myometrium. Enzyme-linked immunosorbent assay was used to measure the serum concentrations of progesterone in pregnant mice. Immunohistochemistry revealed localizations of AQP1, AQP5 mainly in mice myometrium. Progesterone significantly prevented PTB in pregnant mice induced by LPS, without affecting the number of embryos per litter or the rate of atrophic embryos, while also increasing the expression levels of AQPs. In HUSMCs, progesterone upregulated AQP1, AQP5 expression and activated the activity of β-Catenin. Inhibiting β-Catenin with XAV939 eliminated these alterations. Progesterone could prevent PTB in pregnant mice, possibly through upregulating myometrium AQP1, AQP5 expression via activating the activity of β-Catenin.