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The Cytotrophoblast Layer of Human Chorionic Villi Becomes Thinner but Maintains Its Structural Integrity During Gestation¹

Departments of Molecular Anatomy³ and Obstetrics and Gynecology,⁴ Nippon Medical School, Tokyo 113-8602, Japan Department of Physiology and Cell Biology,⁵ Ohio State University, Columbus, Ohio 43210 Department of Obstetrics and Gynecology,⁶ Jichi Medical University, Tochigi 329-0498, Japan Second Department of Pathology,⁷ Faculty of Medicine, Miyazaki University, Miyazaki 889-1692, Japan

ABSTRACT

Chorionic villi in the human placenta serve as essential structures in fetomaternal exchanges. According to the embryology and placentology literature, during the first trimester, the cytotrophoblast (CTB) layer that is subjacent to the syncytiotrophoblast (STB) and supported by a basal lamina is nearly complete, but later, it becomes discontinuous. In the present study, we investigated the structural integrity of the CTB layer in the normal villous tree by advanced microscopy techniques using an antibody to hepatocyte growth factor (HGF) activator inhibitor type 1 (SPINT1), a potent inhibitor of HGF activators expressed exclusively on villous CTB. In full-term placenta, the cell surface of the CTB layer was spread over the basal lamina but was not interrupted. Morphometric analysis showed that throughout the villous tree, 80% of the continuity of the CTB layer of full-term placenta and 90% of that of first-trimester placenta were preserved. Gestation was accompanied by unique structural change in the basal domain of the trophoblast layer. The initially cuboidal-shaped CTB cells were transformed to flat cells with many cellular processes that, together with those of the adjacent STB, eventually covered the trophoblast basal lamina in a complex network of interdigitations. In addition, the expression levels of SPINT1, ST14, HGF, and MET mRNAs in the villous tree increased over the course of gestation. These results suggest that the structural integrity of the SPINT1-positive CTB layer may play an important role in villous differentiation and in maintenance of the villous tree via the HGF signaling system during gestation.

placenta, trophoblast

¹Supported in part by grants-in-aid (nos. 16390479 and 16659457 to T.T. and no. 17791140 to M.M.) from the Ministry of Education, Culture, Sports, Science, and Technology of Japan.

Correspondence: ² Toshihiro Takizawa, Department of Molecular Anatomy, Nippon Medical School, 1-1-5 Sendagi, Tokyo 113-8602, Japan. FAX: 81 3 5685 3052; e-mail: t-takizawa{at}nms.ac.jp