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.