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Review
. 2008 Apr;34(2):129-36.
doi: 10.1111/j.1447-0756.2008.00776.x.

An integrated view of L-selectin and trophinin function in human embryo implantation

Michiko N Fukuda  1 , Kazuhiro Sugihara
Affiliations
Review

An integrated view of L-selectin and trophinin function in human embryo implantation

Michiko N Fukuda et al. J Obstet Gynaecol Res. 2008 Apr.

Abstract

Determining molecular mechanisms of human embryo implantation is an extremely challenging task due to the limitation of materials and significant differences underlying this process among mammalian species. Recently, L-selectin and its ligand carbohydrate have been proposed as a system that mediates initial adhesion of human blastocysts to the uterine epithelia. We have also identified trophinin as a unique apical cell adhesion molecule potentially involved in the initial adhesion of trophectoderm of the human blastocyst to endometrial surface epithelia. In the mouse, the binding between ErbB4 on the blastocyst and heparin-binding epidermal growth factor-like growth factor on the endometrial surface enables the initial step of the blastocyst implantation. The evidence suggests that L-selectin and trophinin are included in human embryo implantation. This review summarizes findings relevant to the functions of L-selectin and trophinin in human embryo implantation, and proposes a model that reconciles these cell adhesion mechanisms.

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Figures

Figure 1
Figure 1. Trophinin in ectopic pregnancy
(a) Hematoxylin-eosin stained specimen of ectopic pregnancy in the fallopian tube. The implantation site is marked by arrowheads. Chorionic villi are marked as CV. Scale bar = 2 mm. (b) High magnification of inset area ‘J’ in (a), stained for trophinin. (c) High magnification of inset area ‘K’ in (a), stained for trophinin. (b) and (c) are shown at the same magnification. Scale bar = 100 μm. Note that trophinin is expressed in the maternal tubal epithelia located close to the implantation site (b). By contrast, trophinin is not found in the maternal epithelia distant from the implantation site (c).
Figure 2
Figure 2. Proposed role of L-selectin and trophinin in human embryo implantation
(a) A human blastocyst entering the uterine cavity is prevented from adhering to endometrial surface epithelia by heavily glycosylated MUC1, except for epithelia that express L-selectin ligand (T). The human blastocyst expresses L-selectin (L), and ‘rolls’ on the endometrial surface covered by glycocalyx (cell surface layer shown by grey color). (b) The blastocyst weakly interacts on the glycocalyx. During this interaction, human chorionic gonadotropin (hCG) secreted from the blastocyst acts locally on endometrial surface epithelia to induce trophinin expression in the endometrial epithelial cells. (c) Trophinin expressed by endometrial epithelia is enriched in the pinopodes, the structure extended above the glycocalyx. MUC1, which is the major component of endometrial glycocalyx and carries L-selectin ligand, is down-regulated from the endometrial surface epithelia underneath the blastocyst, allowing direct contact of blastocyst trophectoderm cells and pinopodes. Trophectoderm cells and pinopodes then bind strongly together by trophinin-trophinin binding.
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