Study the effect of recombinant leukemia inhibitory factor on maintenance of pregnancy and frequency of regulatory T cells in abortion-prone mice

Abstract

Recurrent spontaneous abortion (RSA) can have a significant impact on a woman's quality of life. Understanding the mechanisms behind abortion is crucial for developing potential treatments. Among various models of abortion, the CBA/J(♀) × DBA/2J(♂) model stands out as the most extensively studied. This model reveals the influence of an altered immune system on resorption during pregnancy. The leukemia inhibitory factor (LIF) holds considerable importance as a secretory glycoprotein essential for successful implantation. Regulatory T cells (Tregs) have been found to produce high levels of LIF in both mice and humans. LIF plays a vital role in the development of Tregs by upregulating the expression of the Foxp3 transcription factor while downregulating the expression of RORγt. To investigate the impact of recombinant LIF (rLIF) on pregnancy maintenance and Treg cell frequency in abortion-prone (AP) mice, a specific recombinant protein was used in this study. The AP group consisted of CBA/J(♀) × DBA/2J(♂) mice, while the control group comprised CBA/J(♀) × BALB/c(♂) mice. Intraperitoneal injections of rLIF were administered to the AP group on the third day of pregnancy, and its effects on Treg cell frequency and pregnancy maintenance were examined during this period. Following rLIF injections on the fourteenth day of pregnancy, the expression of Foxp3 significantly increased in AP mice (p = 0.02,0.008). Additionally, AP mice injected with rLIF demonstrated a significant reduction in resorption rate (p = 0.01) and a notable increase in birth rate (p = 0.01,0.0005). These findings provide new insights into the potential benefits of LIF in treating RSA patients.