The first trimester human trophoblast cell line ACH-3P: a novel tool to study autocrine/paracrine regulatory loops of human trophoblast subpopulations--TNF-alpha stimulates MMP15 expression.

BACKGROUND: The 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). RESULTS: Expression 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. CONCLUSION: We 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-alpha on matrix metalloproteinase 15 in HLA-G positive ACH-3P and explants was found.

Timing of referral for prenatal genetic counselling.

OBJECTIVE: To evaluate the timing of referrals for prenatal genetic counselling. METHOD: The data of 406 consecutive patients referred because of a family history of genetic disease or a suspected risk factor for genetic disease other than an unfavourable first trimester screening outcome were retrospectively analysed. RESULTS: In 37.2% (151/406) of included patients, a pregnancy was already ongoing. The mean gestational age at first contact was 13.6 weeks (SD 5.5 weeks). The main counselling issues were previous pregnancy with abortive outcome (ICD O00-O08) 23.9% (97/406), chromosomal abnormalities (ICD Q90-Q99) 16.7% (68/406) and metabolic disorders (ICD E70-E90) 9.9% (40/406). As a result of prenatal genetic counselling, invasive prenatal diagnostic procedures were performed in 11.3% (46/406) of all patients. CONCLUSION: Patients are often referred to prenatal genetic counselling when prenatal diagnosis of a familial genetic condition is no longer feasible, preventive measures are limited and alternative reproductive options have become impossible. Healthcare providers are challenged to improve services so prenatal genetic counselling can take place before conception.