Abstract
BackgroundThe trophoblast compartment of the placenta comprises various subpopulations with distinct functions. They interact among each other by secreted signals thus forming autocrine or paracrine regulatory loops. We established a first trimester trophoblast cell line (ACH-3P) by fusion of primary human first trimester trophoblasts (week 12 of gestation) with a human choriocarcinoma cell line (AC1-1).ResultsExpression of trophoblast markers (cytokeratin-7, integrins, matrix metalloproteinases), invasion abilities and transcriptome of ACH-3P closely resembled primary trophoblasts. Morphology, cytogenetics and doubling time was similar to the parental AC1-1 cells. The different subpopulations of trophoblasts e.g., villous and extravillous trophoblasts also exist in ACH-3P cells and can be immuno-separated by HLA-G surface expression. HLA-G positive ACH-3P display pseudopodia and a stronger expression of extravillous trophoblast markers. Higher expression of insulin-like growth factor II receptor and human chorionic gonadotropin represents the basis for the known autocrine stimulation of extravillous trophoblasts.ConclusionWe conclude that ACH-3P represent a tool to investigate interaction of syngeneic trophoblast subpopulations. These cells are particularly suited for studies into autocrine and paracrine regulation of various aspects of trophoblast function. As an example a novel effect of TNF-α on matrix metalloproteinase 15 in HLA-G positive ACH-3P and explants was found.
Highlights
The trophoblast compartment of the placenta comprises various subpopulations with distinct functions
In a series of differentiation steps the trophoblast subpopulations originate from cytotrophoblast stem cells [1], and acquire specific functions associated with their distinct tasks
The mean diameter and the volume of the cells were greater in both cell lines AC1-1 and ACH-3P than in primary trophoblasts (Table 1)
Summary
The trophoblast compartment of the placenta comprises various subpopulations with distinct functions. In the first trimester of pregnancy the placental trophoblast has to fulfil a wide range of key functions in order to establish and maintain a successful pregnancy. These are not covered by one trophoblast phenotype, but rather associated with various trophoblast subpopulations each with unique features. Two main differentiation pathways of cytotrophoblasts are known: 1) in the villous pathway they differentiate and fuse to form the syncytiotrophoblast. This differentiation is paralleled by the onset of secretion of β-human chorionic gonadotropin (β-hCG). A small subgroup of these cells maintains their proliferative capacity, while most of the cells further differentiate into highly invasive extravillous trophoblasts that invade the maternal uterine wall thereby opening the uterine spiral arteries
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