Azithromycin prevents implantation failure via up-regulation of leukemia inhibitory factor in endotoxemic pregnant rats

Objective(s): Embryonic implantation is a complex and poorly understood process in which numerous cellular, hormonal, and molecular factors play critical roles. Infections in this process can result in pregnancy failure, such as implantation failure, infertility, and spontaneous abortion. Antibiotic use is necessary for infections. However, antibiotic use in pregnancy and the effect of the drug used on implantation are also conditions that must be considered. The implantation site is highly sensitive to lipopolysaccharide (LPS) and tumor necrosis factor (TNF)α, both of which can induce embryonic resorption. This study aimed to determine the effect of azithromycin (AZIT) on implantation failure, an important factor in early embryonic loss caused by LPS, by evaluating TNFα, interleukin (IL)-10, IL-2, and leukemia inhibitory factor (LIF) mRNA expressions in uterine tissue. Materials and Methods: The study involved twenty-six female rats, divided into four groups: Control, Sham, LPS, and LPS+AZIT. Lipopolysaccharide was administered intravenously on the 5th day of pregnancy in the LPS and LPS+AZIT groups. AZIT was administered intraperitoneally in the LPS+AZIT group simultaneously with LPS. TNFα, IL-10, IL-2, and LIF mRNA expressions were evaluated in uterine tissue three hours post-LPS administration. Results: Lipopolysaccharide administration increased the expression of TNFα and IL-2 and decreased the expression of LIF. AZIT prevented the LPS-induced increase in TNFα and IL-2 mRNA expression and the decrease in LIF mRNA expression, all of which are involved in implantation failure. Conclusion: AZIT may support the continuation of pregnancy by preventing the cytokine imbalance caused by infection at implantation.