Serum opacity factor normalizes dysfunctional high density lipoproteins in SRBI -/- female mice and rescues fertility

Abstract

Background and Aims: Previous views about the role of HDL are shifting from, “HDL is good,” to “Some HDL is dysfunctional.” HDL from SR-B1-/- mice is dysfunctional; these mice are atherosusceptible, have dysfunctional erythrocytes and platelets, and females are infertile. Notably, SR-B1-/- mice have high plasma levels of HDL that is free cholesterol (FC)-rich relative to WT mice producing a state of excess FC bioavailability. Dietary probucol, an HDL-lowering drug, partially reverses infertility in SR-B1-/- mice. The mechanisms underlying ovaritoxicity is not known and interventions that fully reverse this state have not been identified. We hypothesized that a bacterial protein, serum opacity factor (SOF), which acts on HDL and lowers cholesterol in WT mice by ∼43% in 3 hours, would normalize HDL and rescue infertility in SRBI -/- female mice.