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Mol. Hum. Reprod. Advance Access originally published online on June 15, 2009
Molecular Human Reproduction 2009 15(8):507-512; doi:10.1093/molehr/gap041
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© The Author 2009. Published by Oxford University Press on behalf of the European Society of Human Reproduction and Embryology. All rights reserved. For Permissions, please email: journals.permissions@oxfordjournals.org

Regulation of myometrial contractivity during pregnancy in the rat: potential role for DDAH

Emiko Ito1, Satoshi Obayashi2,4, Akiko Nagai3, Masatoshi Imamura1 and Hiroshi Azuma1

1Department of Biosystem Regulation, Institute of Biomaterials and Bioengineering, Graduate School, Tokyo Medical and Dental University, Tokyo, Japan 2 Comprehensive Reproductive Medicine, Graduate School, Tokyo Medical and Dental University, 1-5-45 Yushima, Bunkyo-Ku, Tokyo 113-8519, Japan 3Department of Inorganic Materials, Institute of Biomaterials and Bioengineering, Graduate School, Tokyo Medical and Dental University, Tokyo, Japan

4 Correspondence address. E-mail: s.obayashi.gyne{at}tmd.ac.jp

There has been little information demonstrating the roles of dimethylarginine dimethylaminohydrolase (DDAH), which is the hydrolyzing enzyme of endogenous nitric oxide synthase (NOS) inhibitors and, in turn, modulates the intracellular concentrations of NOS inhibitors, in the myometrium during the course of pregnancy. Therefore, the present experiments were designed to investigate whether or not DDAH activity, protein and mRNA expression levels are altered during gestation of the rat and, if altered, those changes reflect on the levels of endogenous inhibitors and endothelin-1 (ET-1), and NO-dependent cyclic GMP generation in the myometrium. The up-regulated changes in DDAH activity, DDAH-2 protein and DDAH-2 mRNA expression at mid-gestation were accompanied by the reduced monomethylarginine and asymmetric dimethylarginine as NOS inhibitors, and ET-1 levels, and by the enhanced NO-dependent cyclic GMP production. At term gestation, on the other hand, down-regulated changes in DDAH activity, DDAH-2 protein and DDAH-2 mRNA expression were accompanied by the increased NOS inhibitors and ET-1 levels, and decreased NO-dependent cyclic GMP generation. These results suggest that alterations in DDAH/NOS inhibitors/NO-dependent cyclic GMP/ET-1 pathway are possibly involved in maintaining myometrial quiescence during gestation and controlling delivery at term.

Key words: DDAH-1 and DDAH-2/MMA and ADMA/NOS/NO-dependent cyclic GMP/endothelin-1

Submitted on March 5, 2009; resubmitted on May 22, 2009; accepted on May 29, 2009.


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