Lipid-altering compositions for the treatment of infertility

Abstract

SR-BI is present at relatively high levels on the membranes of hepatocytes and steroidogenic tissues, including the adrenal gland, testes, and ovaries, where it mediates the uptake and transport of cholesteryl ester from high density lipoproteins. It has been demonstrated that transgenic animals which do not produce SR-BI are healthy, with the exception that the females are infertile. SR-BI KO females have abnormal HDLs, ovulate dysfunctional oocytes and are infertile. Surgical, genetic and pharmacologic methods were used to show that the fertility of SR-BI KO females (or their transplanted oocytes) can be restored in the absence of ovarian and/or extraovarian SR-BI expression by manipulations that modify the structure, composition and/or abundance of their abnormal plasma lipoproteins. These manipulations included inactivation of the apolipoprotein A-I gene and administration of the cholesterol-lowering drug PROBUCOL™. In the absence of treatment, female animals which do not express SR-BI have dramatically reduced levels of offspring, even though they are otherwise healthy and the males normal. Studies demonstrate that they do not produce viable eggs and have a defect involving implantation of normal eggs.