OBJECTIVE: To assess the role of bone morphogenetic protein 4 (BMP4) in decidualization and RSA.
METHODS: Decidual samples were collected from both RSA patients and healthy controls to assess BMP4 expression. In vitro cell experiments utilized the hESC cell line to investigate the impact of BMP4 on decidualization and associated aging, as well as its role in the maternal-fetal interface communication. Subsequently, a spontaneous abortion mouse model was established to evaluate embryo resorption rates and BMP4 expression levels.
RESULTS: Our study identified a significant downregulation of BMP4 expression in the decidua of RSA patients compared to the normal control group. In vitro, BMP4 knockdown resulted in inadequate decidualization and inhibited associated aging processes. Mechanistically, BMP4 was implicated in the regulation of FOXO1 expression, thereby influencing decidualization and aging. Furthermore, loss of BMP4 hindered trophoblast migration and invasion via FOXO1 modulation. Additionally, BMP4 downregulation was observed in RSA mice.
CONCLUSIONS: Our findings highlighted the downregulation of BMP4 in both RSA patients and mice. BMP4 in human endometrial stromal cells was shown to modulate decidualization by regulating FOXO1 expression. Loss of BMP4 may contribute to the pathogenesis of RSA, suggesting potential avenues for abortion prevention strategies.
方法:从RSA患者和健康对照收集蜕膜样本以评估BMP4表达。体外细胞实验利用hESC细胞系来研究BMP4对蜕膜化和相关衰老的影响,以及它在母胎界面通信中的作用。随后,建立自然流产小鼠模型以评估胚胎吸收率和BMP4表达水平。
结果:我们的研究发现,与正常对照组相比,RSA患者蜕膜中BMP4表达的显着下调。体外实验表明,BMP4敲低导致蜕膜化不足,并抑制了相关的衰老过程。机械上,BMP4与FOXO1表达的调节有关,从而影响蜕膜化和衰老。此外,BMP4的丢失通过FOXO1调节阻碍了滋养层的迁移和入侵。此外,在RSA小鼠中观察到BMP4下调。
结论:我们的发现强调了BMP4在RSA患者和小鼠中的下调。显示人子宫内膜基质细胞中的BMP4通过调节FOXO1表达来调节蜕膜化。BMP4的缺失可能与RSA的发病机制有关。提出了预防堕胎策略的潜在途径。