Abstract
Background: Observational and retrospective studies suggest that liposomes may be associated with female infertility. The exact relationship between different liposomes and female infertility remains difficult to determine. In addition, modulation of the immune system is a key measure of the impact of lipids on disease development, but it remains uncertain whether the causality of this association is mediated by immune cells.
Method:In this study, we performed a two-step two-sample Mendelian randomization (MR) analysis to investigate the causal role of lipids on female infertility and the mediating role of immune cells between lipids and female infertility. The inverse variance weighting method was employed as the primary estimator, complemented by MR-Egger, Weighted median, Simple mode, and Weighted mode approaches. To address potential bias from single nucleotide polymorphisms (SNPs), we utilized MR-PRESSO. Additionally, Cochran's Q test and MR-Egger intercept analysis were performed to detect heterogeneity and horizontal pleiotropy.
Results: MR analysis identified a causal relationship between 18 lipid species and female infertility. In addition,14 immune cell traits suggested an association with female infertility. Notably, mediated MR showed that the causal effect of phosphatidylcholine on female infertility (Total effect IVW: OR=1.069,95% CI [1.008,1.134], P=0.030) was largely mediated by HLA DR++ monocyte AC (OR=0.888,95% CI [0.790,0.998] , P=0.046).
Conclusion:This study demonstrates a causal relationship between liposomes and female infertility, which may be mediated by HLA DR++ monocyte AC, thereby identifying novel drug targets for the prevention and treatment of this condition.