Icaritin attenuates recurrent spontaneous abortion in mice by modulating Treg/Th17 imbalance via TGF-13/SMAD signaling pathway

Recurrent spontaneous abortion (RSA) is a challenging global issue. Although the cause is unknown, increasing evidence suggests that immunological factors play a crucial role in RSA development. Icaritin (ICT), a natural compound derived from Epimedium, has demonstrated diverse biological activities, including antiinflammatory, anti-cancer, and immunomodulatory effects. In this study, we aimed to investigate the potential therapeutic role of ICT in mitigating RSA in a mouse model. Specifically, we sought to determine whether ICT could modulate the Treg/Th17 cell imbalance via the TGF-13/SMAD signaling pathway and contributed to improved pregnancy outcomes. We conducted experiments on a mouse model with RSA and administered ICT orally. We then examined the effects of ICT on various types of immune cells including Treg and Th17 cells, and assessed the pregnancy outcomes. We also investigated the potential signaling pathway ICT exerted its effects. Our findings revealed that treatment with ICT led to an increase in Treg cells and a decrease in Th17 cells, which restored immune homeostasis and contributed to improved pregnancy outcomes. Furthermore, our data demonstrated that ICT's effects were mediated through the activation of TGF-13/SMAD signaling components. In conclusion, our study suggested that ICT ameliorated RSA by modulating Treg/Th17 cell imbalance via the TGF13/SMAD signaling pathway. General significance: Our results highlighted the potential of ICT as a novel therapeutic agent for RSA, offering new insights into the underlying mechanisms and opening avenues for future research and clinical translation.