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Reproductive Sciences
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Modulation of Matrix Metalloproteinase Secretion by Adenosine A3 Receptor in Preeclamptic Villous Explants

Young-Han Kim, MD, PhD

Department of Obstetrics and Gynecology, Yonsei University Health System, Seoul, Korea

Han-Sung Hwang, MD

Department of Obstetrics and Gynecology, Yonsei University Health System, Seoul, Korea

Young-Tae Kim, MD, PhD

Department of Obstetrics and Gynecology, Yonsei University Health System, Seoul, Korea

Haeng-Soo Kim, MD, PhD

Department of Obstetrics and Gynecology, Ajou University College of Medicine, Suwon, South Korea

Yong-Won Park, MD, PhD

Department of Obstetrics and Gynecology, Yonsei University Health System, Seoul, Korea, ywparkob{at}yumc.yonsei.ac.kr

The impairment of trophoblast invasion associated with preeclampsia may involve matrix metalloproteinase (MMP). Adenosine A3 receptors expression in trophoblast is upregulated in preeclampsia. This study was designed to determine if A3 receptors modulate MMP secretion in villous explants from preeclamptic pregnancies. Villous explants from normal and preeclamptic pregnancies were cultured at 20% and 3% oxygen. There were significantly increased A3 receptor and reduced MMP-2/-9 expression at low oxygen level in normal and preeclamptic explants. Interestingly, in preeclamptic explants, after high oxygen culture, the expression of MMP-2/-9 were recovered to almost same level of those in normal explants. Treatment of preeclamptic explants with A3 receptor agonist in low oxygen level resulted in an enhanced expression of MMP-2/-9 in a time- and dose-dependent manner. In summary, this study indicates that trophoblastic adenosine A3 receptors are 1) modulated by oxygen tension, and 2) regulate MMP-2/-9 expression.

Key Words: adenosine A3 receptor • matrix metalloproteinase • preeclampsia • villous explants.

Reproductive Sciences, Vol. 15, No. 9, 939-949 (2008)
DOI: 10.1177/1933719108322431
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