The Impact of Leukemia Inhibitory Factor on Sirtuin1 , Ilt‐4 , and Related microRNAs Expression in a Mouse Model of Recurrent Pregnancy Loss

Purpose Leukemia Inhibitory Factor (LIF) plays a crucial role in implantation and early pregnancy maintenance. However, its regulatory relationships with molecular markers such as Sirtuin 1 (SIRT1), immunoglobulin‐like transcript 4 (ILT‐4), and specific microRNAs (miRNA) in recurrent pregnancy loss (RPL) remain underexplored. Methods This study investigates the effect of LIF on the expression of Sirt1 , Ilt‐4 , and related miRNAs using a mouse model of RPL. Female CBA/J mice mated with DBA/2 J males received LIF treatment. Gene and miRNA expression levels were assessed via quantitative PCR. Results The LIF‐treated group showed significant upregulation of Sirt1 on Days 7 and 14. Ilt‐4 expression also increased significantly on Days 7 and 14 in the LIF group. Among miRNAs, mir‐138‐5p was significantly upregulated on Day 14 ( p = 0.0001), while mir‐223‐3p was downregulated on Days 7 ( p = 0.02) and 14 ( p = 0.001). mir‐199a‐5p showed significant downregulation on Days 7 ( p < 0.0001) and 14 ( p = 0.0001). Additionally, mir‐155‐5p demonstrated a significant decrease in the LIF‐treated group compared to the PBS group ( p < 0.0001). Conclusions These results suggest that LIF modulates critical molecular pathways in RPL by influencing the expression of essential genes and miRNAs, highlighting its potential as a therapeutic target for pregnancy‐related complications.