Autotaxin as a novel, tissue-remodeling-related factor in regressing corpora lutea of cycling rats

Autotaxin (ATX) generates lysophosphatidic acid (LPA) from glycerophospholipid via lysophospholipase D (lysoPLD) activity in cooperation with phospholipase A. We studied its expression and possible functional roles in the ovary of nonfertile cycling rats. Immunohistochemistry revealed that ATX was located predominantly in luteal steroidogenic cells of corpora lutea (CL), but not in any follicles. ATX expression was modest in the newest generation of CL and augmented in older generations undergoing structural regression. ATX expression in the whole ovary and lysoPLD activity in circulating blood did not alter during the estrous cycle. Among the LPA receptors examined (LPA1-4 ), LPA4 was densely present on migratory cells, probably phagocytes, at degenerative foci within regressing CL. Bolus administration of anti-ATX IgG or LPA into ovarian bursa in vivo had little effect on the apoptotic cell death of luteal cells, as evaluated by cleaved caspase 3 expression, but led to altered numbers of neutrophils and macrophages in regressing CL, as evaluated by immunological detection of each cell marker. These treatments, together with bromodeoxy uridine, revealed a stimulatory effect of the ATX/LPA pathway on fibroblast proliferation in regressing CL. The results indicate that ATX is increasingly expressed by structurally regressing CL and has definite local action on phagocyte recruitment and fibroblast proliferation which are responsible for tissue remodeling.