Implantation-dependent expression of trophinin by maternal fallopian tube epithelia during tubal pregnancies: possible role of human chorionic gonadotrophin on ectopic pregnancy

Abstract

Trophinin, tastin, and bystin have been identified as molecules potentially involved in human embryo implantation. Both trophoblasts and endometrial epithelial cells express trophinin, which mediates apical cell adhesion through homophilic trophinin-trophinin binding. We hypothesized that trophinin's function in embryo implantation is unique to humans and investigated the expression of trophinin, tastin, and bystin in ectopic pregnancy, a condition unique to humans. In tubal pregnancies, high levels of all three were found in both trophoblasts and fallopian tubal epithelia. Trophinin expression in maternal cells was particularly high in the area adjacent to the trophoblasts, whereas trophinin was barely detectable in intact fallopian tubes from women with in utero pregnancies or without pregnancies. When explants of intact fallopian tube were incubated with the human chorionic gonadotrophin (hCG), trophinin expression was enhanced in epithelial cells. Since the trophectoderm of the human blastocyst secretes hCG before and after implantation, these results suggest that hCG from the human embryo induces trophinin expression by maternal cells. As both beta-subunit of hCG and trophinin genes have diverged in mammals, the present study suggests a unique role of hCG and trophinin in human embryo implantation, including the pathogenesis of ectopic pregnancy.

Figure 1.

Expression of trophinin, tastin, and bystin proteins and their transcripts in the chorionic villi from tubal pregnancy. Immunohistochemistry for trophinin (A), tastin (B), bystin (C), second antibody alone (D), and in situ hybridization for trophinin (E, antisense; H, sense), tastin (F, antisense; I, sense), and bystin (G, antisense; J, sense) using digoxigenin-labeled RNA probes. All photographs presented are in the same magnification, and the bar in (J) indicates 200 μm. (cv, chorionic villi; t, trophoblasts).

Figure 2.

Expression of trophinin, tastin, and bystin proteins in intact fallopian tube and in fallopian tube with tubal pregnancy. Immunohistochemistry of an intact fallopian tube (A–D) and a fallopian tube with tubal pregnancy (E–K) for trophinin (A, E, J, K), tastin (B, F), and bystin (C, G). Hematoxylin and eosin-stained specimen from a tubal pregnancy (I), and high magnification of insets showing immunohistochemistry for trophinin in the area close to (J) or distant from (K) the chorionic villi. The implantation site in (I) is marked by arrowheads. All photographs except (I) are in the same magnification, and the bar in (K) indicates 100 μm. Bar in (I) indicates 2.0 mm. (cv, chorionic villi; te, tubal epithelia).

Figure 3.

Expression of trophinin, tastin, and bystin transcripts in intact fallopian tube and in that with tubal pregnancy. In situ hybridization of an intact fallopian tube (A–F), and a fallopian tube with tubal pregnancy (G–L) for trophinin (A and G, antisense; D and J, sense), tastin (B and H, antisense; E and K, sense), and bystin (C and I, antisense; F and L, sense) using digoxigenin-labeled RNA probes. All photographs presented are in the same magnification, and the bar in (L) indicates 200 μm. (te, tubal epithelia).

Figure 4.

Comparison of trophinin, tastin, and bystin proteins in explants of intact fallopian tube with or without incubation with hCG. Explants were cultured for 24 hours without hCG (A–D) or with 100 IU/ml hCG (E–H), and were immunostained for trophinin (A, E), tastin (B, F), bystin (C, G), and second antibody alone (D, H). All photographs presented are in the same magnification, and the bar in (H) indicates 50 μm. (te, tubal epithelia).