Trophoblast dysfunction is a major factor in defect placentation, which is thought to be an important etiology of abortions. Homeobox genes are transcription factors that regulate the transcription of other genes. They encode highly conserved DNA-binding domains (homeodomains) that regulate proliferation, differentiation and migration, important for pattern formation and organogenesis during embryogenesis in the development ofmulticellular organisms. Homeobox genes have also been shown to control normal development of the placenta. They are thought to play an important role in trophoblast proliferation and differentiation. Chloride channels are important in many cellular processes like electrolyte transport, pH regulation, water balance, cell potensials and apoptosis. Little is known about their involvement in trophoblasts and placentation.
Our thesis consists of a literature review related to placenta, placentation, trophoblasts, homeobox genes, ion channel proteins and abortion. It also comprises a pilot study testing our hypothesis: that spontaneous/missed abortions and hydatiform mole are consequences of defect trophoblast function and signalling of homeobox genes in trophoblasts in the placental bed. We also studied the expression of an intracellular ion channel gene called CLIC3.The pilot study was performed on a diagnostic material from first trimester abortions, partly in Oslo and partly at the Pregnancy Research Centre at the University of Melbourne.
Material: Tissue micro arrays (TMAs) from the placental bed in normal (therapeutic abortions) and abnormal (spontaneous and missed abortions and moles) first trimester pregnancies.
Methods: Immunohistochemical study of expression of the homeobox genes TGIF and HEX and the intracellular ion channel CLIC3.
Results: There was a reduction in the expression of Homeobox genes TGIF and HEX and of the ion channel protein CLIC3 in the extravillous trophoblasts in the placental bed in the clinical abortions as compared to the normal controls (therapeutic abortions). The reduced expression was most markedly for HEX in missed abortions. The findings might indicate a defect trophoblast function in clinical first trimester abortions. The staining pattern in the positive cells varied, especially in the homeobox immunostainings. Further studies are needed.