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-Tocopherol Transfer Protein Is Specifically Localized at the Implantation Site of Pregnant Mouse Uterus

^a Graduate School of Pharmaceutical Sciences, Department of Health Chemistry, University of Tokyo, Bunkyo-ku, 113-0033 Tokyo, Japan ^b Division of Neonatology, Department of Pediatrics, University of Heidelberg, D-69120 Heidelberg, Germany ^c Pharmaceutical Technology Laboratory, Chugai Pharmaceutical Co., Ltd., Gotemba, 412-8513 Shizuoka, Japan ^d Department of Pediatrics, Osaka Medical College, 569-8686 Takatsuki-shi, Japan

-Tocopherol transfer protein (-TTP) was first described to play a major role in maintaining -tocopherol levels in plasma, while -tocopherol was primarily reported to be a factor relevant for reproduction. Expression of -TTP is not only seen in the liver, from where it was first isolated, but also in mouse uterus, depending on its state of pregnancy, stressing the importance of -TTP for embryogenesis and fetal development. The cellular localization of -TTP in mouse uterus is reported here. By immunohistochemistry, -TTP could be localized in the secretory columnar epithelial cells of the pregnant uterus on Days 4.5 and 6.5 postcoitum as well as in the glandular epithelial cells and the inner decidual reaction zone surrounding the implantation site. On Days 8.5 and 10.5 postcoitum (midterm of mouse pregnancy), -TTP could still be detected in the uterine secretory columnar epithelial cells, while in -TTP knockout mice, no immunostaining was visible. It is suggested that -TTP plays a major role in supplying the placenta and consecutively the fetus with -tocopherol throughout pregnancy. We conclude that -tocopherol plays a role in the process of implantation and that -TTP may be necessary for adequate -tocopherol status of the fetus.

First decision: 15 January 2002.

¹ The first author thanks the Novartis Foundation (Japan) for the Promotion of Science for the grant of Japan-Europe Scientists Exchange Program 2001.

² Correspondence: Hiroyuki Arai, University of Tokyo, Graduate School of Pharmaceutical Sciences, Department of Health Chemistry, Hongo 7-3-1, Bunkyo-ku, 113-0033 Tokyo, Japan. FAX: 81 3 3818 3173; harai{at}mol.f.u-tokyo.ac.jp

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