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Journal of Nippon Medical School

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Differential Expression of ADAM (a Disintegrin and Metalloproteinase) Genes between Human First Trimester Villous and Extravillous Trophoblast Cells

Hironori Takahashi1,2, Kazuya Yuge2, Shigeki Matsubara1, Akihide Ohkuchi1, Tomoyuki Kuwata1, Rie Usui1, Mitsuaki Suzuki1 and Toshihiro Takizawa2

1Department of Obstetrics and Gynecology, Jichi Medical University
2Department of Molecular Medicine and Anatomy, Nippon Medical School


A disintegrin and metalloproteinases (ADAMs) are members of the metzincin family of zinc-dependent metalloproteinases that play pivotal roles in the proteolytic degradation of the extracellular matrix for cell invasion. Few studies have investigated the ADAM subtypes that are expressed in first trimester trophoblast cells. The purpose of this study was to elucidate the differential expression profiles of ADAMs between first trimester villous trophoblast cells (VTs) and extravillous trophoblast cells (EVTs). We isolated EVTs from explanted human first trimester chorionic villi and investigated the mRNA expression levels of five members of the ADAM family (ADAMTS1, ADAMTS2, ADAM10, ADAM12, and ADAM17) using real-time PCR. Chorionic villous tips were defined as first trimester VTs. Of the differentially expressed ADAM genes between first trimester VTs and EVTs, ADAMTS1 was expressed at a significantly higher level in EVTs than in VTs. In contrast, both ADAM10 and ADAM12 were expressed at significantly higher levels in VTs than in EVTs. No differences were found in the mRNA levels of ADAMTS2 and ADAM17 between the two cell types. Moreover, we demonstrated that in VTs, the expression level of ADAM12 was significantly downregulated in the late first trimester (10-13 gestational weeks) compared to the middle first trimester (7-8 weeks). These results suggest that first trimester trophoblast cells express ADAM genes in cell type- and gestational age-dependent manners. Our data provide additional insight into the functions of ADAMs in the human placenta.

J Nippon Med Sch 2014; 81: 122-129

Keywords
a disintegrin and metalloproteinase, extravillous trophoblast cell, cell invasion, villous trophoblast cell, human first trimester placenta

Correspondence to
Toshihiro Takizawa, MD, PhD, Department of Molecular Medicine and Anatomy, Nippon Medical School, 1-1-5 Sendagi, Bunkyo-ku, Tokyo 113-8602, Japan
t-takizawa@nms.ac.jp

Received, November 12, 2013
Accepted, December 9, 2013