The role of cholesterol in female reproductive physiology has been suspected for a long time, while the molecular bases were unknown. Cholesterol is the precursor of ovarian steroid biosynthesis and i Show more
The role of cholesterol in female reproductive physiology has been suspected for a long time, while the molecular bases were unknown. Cholesterol is the precursor of ovarian steroid biosynthesis and is also essential for fertility. In the uterus, cholesterol is essential to achieve correct contractions at term, but an excessive uterine cholesterol concentration has been associated with contractility defects. Liver X Receptor (LXR) α and LXR β are nuclear receptors activated by oxysterols, oxidized derivatives of cholesterol. Since their discovery, the role of LXR in the control of cholesterol homeostasis has been widely described. Beyond their cholesterol-lowering role, more recent data have linked these nuclear receptors to various physiological processes. In particular, they control ovarian endocrine and exocrine functions, as well as uterine contractility. Their contribution to female reproductive cancers will also be discussed. This review will try to enlighten on the LXR as a molecular link between dietary cholesterol and reproductive diseases in women. In the future, a better comprehension of the various physiological processes regulated by the LXR will help to develop new ligands to prevent or to cure these pathologies in women. Show less
Preeclampsia is a frequent complication of pregnancy and a leading cause of perinatal mortality. Both genetic and environmental risk factors have been identified. Lipid metabolism, particularly choles Show more
Preeclampsia is a frequent complication of pregnancy and a leading cause of perinatal mortality. Both genetic and environmental risk factors have been identified. Lipid metabolism, particularly cholesterol metabolism, is associated with this disease. Liver X receptors alpha (NR1H3, also known as LXRalpha) and beta (NR1H2, also known as LXRbeta) play a key role in lipid metabolism. They belong to the nuclear receptor superfamily and are activated by cholesterol derivatives. They have been implicated in preeclampsia because they modulate trophoblast invasion and regulate the expression of the endoglin (CD105) gene, a marker of preeclampsia. The aim of this study was to investigate associations between the NR1H3 and NR1H2 genes and preeclampsia. We assessed associations between single nucleotide polymorphisms of NR1H3 (rs2279238 and rs7120118) and NR1H2 (rs35463555 and rs2695121) and the disease in 155 individuals with preeclampsia and 305 controls. Genotypes were determined by high-resolution melting analysis. We then used a logistic regression model to analyze the different alleles and genotypes for those polymorphisms as a function of case/control status. We found no association between NR1H3 SNPs and the disease, but the NR1H2 polymorphism rs2695121 was found to be strongly associated with preeclampsia (genotype C/C: adjusted odds ratio, 2.05; 95% CI, 1.04-4.05; p = 0.039 and genotype T/C: adjusted odds ratio, 1.85; 95% CI, 1.01-3.42; p = 0.049). This study provides the first evidence of an association between the NR1H2 gene and preeclampsia, adding to our understanding of the links between cholesterol metabolism and this disease. Show less