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Increased Production of Bioactive Lysophosphatidic Acid by Serum Lysophospholipase D in Human Pregnancy¹

^a Laboratory of Health Chemistry, Faculty of Pharmaceutical Sciences, The University of Tokushima, Shomachi, Tokushima 770-8505, Japan ^b Department of Obstetrics and Gynecology, School of Medicine, The University of Tokushima, Kuramoto-cho, Tokushima 770-8503, Japan

Lysophosphatidic acid (LPA) is a prototype of the lysophospholipid mediator family and has multiple effects in the female reproductive system. Although several metabolic routes have been reported for intracellular formation of LPA, a unique route involving lysophospholipase D, an extracellular enzyme that produces LPA in blood and body fluids, is particularly intriguing for its agonistic role. In this study, using an assay with radioactive palmitoyl-lysophosphatidylcholine, we found that lysophospholipase D activity producing palmitoyl-LPA in human serum gradually increased during pregnancy. Elevated activity of lysophospholipase D was not caused by changes in levels of their precursors, lysophosphatidylcholines, in nonpregnant women or in pregnant women at different gestational periods. With increasing length of gestation, the elevated activity in pregnant women was found to produce increasing proportions of LPA with a palmitoyl group versus other LPAs. These results suggest that LPA formed by increased activity of lysophospholipase D in blood might participate in maintenance of pregnancy.

¹ Supported in part by a Grant-in-Aid for scientific research (C) from the Ministry of Education, Culture, Sports and Technology of the Japanese government.

² Correspondence: Akira Tokumura, Faculty of Pharmaceutical Sciences, The University of Tokushima, 1-78-1 Shomachi, Tokushima 770-8505, Japan. FAX: 81 88 633 9572; tokumura{at}ph.tokushima-u.ac.jp

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