[Shoutai Wan improves endometrial decidualization by regulating BRD4 to activate Wnt4/β-catenin signaling pathway].

This study aimed to investigate the effects of Shoutai Wan(STW) on bromodomain-containing protein 4(BRD4) and the Wnt family member 4(Wnt4)/β-catenin signaling pathway, and to explore its potential mechanism in promoting endometrial decidualization for the treatment of recurrent spontaneous abortion(RSA). A mouse model of RSA was established, and CBA/J female mice were randomly divided into five groups(n=10 per group): normal group, model group, low-dose STW group(7.5 g·kg~(-1)), high-dose STW group(15 g·kg~(-1)), and dydrogesterone group(0.003 g·kg~(-1)). From gestational day 1(GD1), mice in the low-dose STW, high-dose STW, and dydrogesterone groups received intragastric administration of the respective drugs, while mice in the normal and model groups were given distilled water instead, for 10 consecutive days. Uterine and decidual tissues were collected on GD10. Human endometrial stromal cells(HESCs) were cultured in vitro, and a decidualization model was induced using dibutyryl cyclic AMP(db-cAMP) combined with medroxyprogesterone acetate(MPA). Cells were incubated with STW-containing serum, and BRD4 was either overexpressed or knocked down, followed by further incubation with STW-containing serum. Hematoxylin and eosin(HE) staining was performed to assess endometrial decidualization. Western blot was used to measure the protein expression levels of BRD4, insulin-like growth factor-binding protein-1(IGFBP-1), prolactin(PRL), Wnt4, and β-catenin. Immunohistochemistry was conducted to detect the expression of BRD4, Wnt4, and β-catenin in decidual tissues. The results showed that STW improved endometrial decidualization in RSA mice, and enhanced the expression of PRL and IGFBP-1 proteins, thereby promoting decidualization. STW promoted endometrial decidualization by activating the Wnt4/β-catenin signaling pathway via BRD4.