Discussion and Conclusion
The results of this study clearly demonstrate that two types of interstitial trophoblast cell populations are present in the first trimester human decidua with distinct phenotypes. They have been designated as type I electron-lucent agranular and type II electron-dense granular interstitial trophoblast cells.
The type I electron-lucent cells represent the majority of the interstitial trophoblast cells, comprising approximately 80% of this decidual cell population. They show marked pleomorphism, the predominant morphological phenotype being spindle-shaped as previously described (Loke & King, 1995). The invaginations on the cell membrane of the interstitial trophoblast suggests that they may be involved in pinocytic and/or endocytic function. Similar findings have been reported in first trimester human uteri (Lawn et al., 1971) and in rats (Tachi et al., 1970). However, it is difficult to determine from static images whether a given flask-like vesicle is exocytotic or endocytotic.
The dark appearance of the trophoblast may be due to the high content of rough endoplasmic reticulum and ribosomes which also suggests they are in a highly active state (Tekelioglu-Uysal et al., 1975). There appears to be a gradual depletion in the glycogen content as the cells move down the cell columns into the decidual stroma. This observation indicates they are highly metabolic cells, utilising glycogen during their invasion in the maternal stroma.
The type II electron-dense interstitial trophoblast, on the other hand, possess a lobate nucleus and cytoplasm rich in electron-dense granules. Although morphologically different from the type I electron-lucent interstitial trophoblast they share a few features such as marked pleomorphism, numerous cytoplasmic processes in their outer membrane, and a dark nuclear chromatin pattern. The electron dense granules and well developed rough endoplasmic reticulum suggests the cells are very active (Wynn, 1972). Immunohistochemical studies have reported that only a proportion of interstitial trophoblast in early pregnancy are reactive with antibodies to hPL (Kurman et al., 1984a) and for leucine amino-peptidase (Butterworth, 1985). Our results here show the cytoplasmic granules of the type I and II cells are reactive for hPL with the type II cells showing the strongest reactivity. In vitro studies have reported the production of both hPL and hCG when interstitial trophoblasts are stimulated by epidermal growth fac tor (Maruo et al., 1995). This suggests that cytokines may possibly be involved in stimulating the production of placental hormones. HPL and hCG as immunosuppressive agents has been reported (Adcock et al., 1973) to play a significant role in allowing implantation of the fetus without rejection. Interstitial trophoblasts have also been shown to express cytokines such as tumour necrosis factor-alpha, transforming growth factor-Beta, interleukin-1Beta, -2, and –6, interferon-alpha and -Beta, granulocyte-macrophage colony stimulating factor and colony stimulating factor-1 (Jokhi, 1994; Aboagye-Methiesen et al., 1994; Paulesu et al., 1994; Yamaguchi et al., 1994; Loke & King., 1995; King et al., 1995 and Bennett et al., 1996). Cytokines may form an important communication network between the mother and fetus and may play a role in regulating critical reproductive events. The extent of trophoblast migration must be finely regulated by the decidua if pregnancy is to be maintained. It is possible that the interstiti al trophoblast may be involved in maintaining the balance between invasion and decidual protection. The considerable numbers of interstitial trophoblasts in the decidua basalis and their absence in the parietal decidua suggest they play a role in placentation.
The immunocytochemical results here show the two cell populations to be reactive for cytokeratin which indicate their trophoblastic nature and confirm their epithelial origin (Loke et al., 1986).
We suggest that the type II cells are trophoblastic for many reasons. Firstly, they share many ultrastructural characteristics with the type I electron-lucent interstitial trophoblast. Secondly, the cytokeratin staining is not blocked by prior treatment with a neat rabbit serum to eliminate non-specific Fc-receptor binding. Thirdly, these cells are not reactive with the monoclonal antibody directed to leucocyte common antigen or neutrophil elastase or CD56 or HAM-56. In addition, the type II electron-dense cells are not present in sections from the parietal decidua and areas of necrosis were selectively avoided before viewing with the electron microscope. It would seem that the interstitial trophoblast migrates into the decidual stroma as two morphologically distinct cell types. This observation confirms the heterogeneity of trophoblast at the feto-maternal interface (Loke et al., 1986).
The similarities between type I and II interstitial trophoblast cells such as positive immunoreaction for cytokeratin and hPL suggest their common origin. The type I electron-lucent interstitial trophoblasts may be precursors of the type II electron-dense cells and as the former migrate into the maternal decidua in early pregnancy, they differentiate into two pathways. Alternatively, the type II cells possibly represent an effete population which have lost its invasive abilities and do not form giant cells as characteristic of type I cells. They could, therefore, represent the end-stage of interstitial trophoblast cell differentiation and may be programmed to die. A proportion of the type II cells show fine morphology reminiscent of apoptosis. This could be a hormone process of differentiation during trophoblast cell invasion in the maternal decidua. Whatever their role, it is intriguing that they are able to co-exist with various maternal cells in an allogeneic environment without any deleterious e ffect.
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|Al-Lamki, R.S; Skepper, J.N; Wooding, P.B.P; Burton, G.J; (1998). The Interstitial Trophoblast of the First Trimester Human Decidua Basalis Is Composed of Two Distinct Cell Types: an Ultrastructural and Immunocytochemical Study. Presented at INABIS '98 - 5th Internet World Congress on Biomedical Sciences at McMaster University, Canada, Dec 7-16th. Available at URL http://www.mcmaster.ca/inabis98/cellbio/al-lamki0114/index.html|
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