The LOX-1 receptor, identified on endothelial cells, mediates the uptake of oxLDL (oxidized low-density lipoprotein). The oxLDL dependent LOX-1 activation causes endothelial cell apoptosis. We here investigated the presence of LOX-1 in granulosa cells from patients under in vitro fertilization (IVF) therapy. We were interested in the oxLDL dependent LOX-1 receptor biology, in particular in the induction of apoptosis.

In the human ovary, LOX-1 was localized in regressing antral follicles. In granulosa cell cultures, oxLDL induced mRNA expression of LOX-1 in a time- and dose-dependent manner. The LOX-1 inhibitors (anti-LOX-1 antibody and -carrageenan) abrogated the up-regulation of LOX-1. The oxLDL (100 µg/ml) treatment caused the autophagy form of programed cell death: (1) reorganisation of the actin cytoskeleton at the 6-h-time point, (2) uptake of YO-PRO©, a marker for the early step of programed cell death, before propidium iodide (PI) staining to signify necrosis, (3) absence of apoptotic bodies and of cleaved caspase-3, (4) abundant vacuole formation at the ultrastructural level, (5) decrease of the autophagosome marker protein MAP LC3-I at the 6-h-time point indicative of autophagosome formation. We conclude: Follicular atresia is not under the exclusive control of apoptosis. The LOX-1-dependent autophagy represents an alternate form of programed cell death. Obese women with high blood levels of oxLDL may display an increased rate of autophagic granulosa cell death.