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Journal of Biomedicine and Biotechnology
Volume 2011, Article ID 286947, 12 pages
Review Article

Placental Leucine Aminopeptidase- and Aminopeptidase A- Deficient Mice Offer Insight concerning the Mechanisms Underlying Preterm Labor and Preeclampsia

1Daiya Building Lady's Clinic, Meieki 3-15-1, Nakamura, Nagoya 450-0002, Japan
2Department of Psychology, Veterinary and Comparative Anatomy, Pharmacology and Physiology, and Programs in Neuroscience and Biotechnology, Washington State University, Pullman, WA 99164-4820, USA
3Department of Obstetrics-Gynecology, Nara Medical University, 840 Shijo-cho, Kashihara, Nara 634-8522, Japan

Received 6 August 2010; Accepted 8 October 2010

Academic Editor: Monica Fedele

Copyright © 2011 Shigehiko Mizutani et al. This is an open access article distributed under the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.


Preeclampsia and preterm delivery are important potential complications in pregnancy and represent the leading causes for maternal and perinatal morbidity and mortality. The mechanisms underlying both diseases remain unknown, thus available treatments (beta2-stimulants and magnesium sulfate) are essentially symptomatic. Both molecules have molecular weights less than 5–8 kDa, cross the placental barrier, and thus exert their effects on the fetus. The fetus produces peptides that are highly vasoactive and uterotonic and increase in response to maternal stress and with continued development. Fetal peptides are also small molecules that inevitably leak across into the maternal circulation. Aminopeptidases such as placental leucine aminopeptidase (P-LAP) and aminopeptidase A (APA) are large molecules that do not cross the placental barrier. We have shown that APA acts as an antihypertensive agent in the pregnant spontaneously hypertensive rat by degrading vasoactive peptides and as a result returns the animal to a normotensive state. P-LAP also acts as an antiuterotonic agent by degrading uterotonic peptides and thus prolongs gestation in the pregnant mouse. Given the ever increasing worldwide incidences of preeclampsia and preterm labor, it is imperative that new agents be developed to safely prolong gestation. We believe that the use of aminopeptidases hold promise in this regard.