Mouse oocytes exposed to excess cholesterol can activate prematurely. New findings hint that abnormal cholesterol metabolism may contribute to some cases of human infertility (1).

Previous experiments had suggested that the infertility of SR-BI-deficient mice was due to defects in oocytes and eggs around the time of ovulation. The researchers looked more closely and found that eggs were prematurely activated—exiting meiosis II and completing meiotic progression, a process that normally occurs only after fertilization. The researchers then asked if excess cholesterol could induce premature activation; they treated normal eggs with a molecular complex containing cholesterol. This cholesterol loading prematurely activated the eggs, possibly because of an excess of the unesterified form of cholesterol. The treatment also induced a single spike in intracellular calcium; induction of multiple calcium spikes is a key early stop in egg activation by sperm. Future studies should unravel the molecular events that prompt egg activation by excess cholesterol and help determine if there is a connection with dietary hypercholesterolemia. It is also possible that this mechanism may contribute to some cases of human infertility of unknown cause.