Differential expression of trophoblast-, endothelial- and embryonic-stem-cell-associated transcription factors in 1st trimester, and 3 rd trimester preeclampsia (PE), intrauterine growth factor (IUGR) and control placentae

Objectives: Stem cells are highly proliferative, undifferentiated cells and stem cell-associated markers (SCM) are involved in maintaining these characteristics. Trophoblast progenitor cells are known to express these markers, and are cells which replenish the outer syncytiotrophoblast layer when necessary. Little data is available characterizing the expression of SCMs beyond the blastocyst stage or during pregnancy pathologies. We aimed to describe the expression of trophoblast and other SCMs in the placenta of 1 st and 3 rd trimester, but also of preeclampsia (PE) and intrauterine growth retardation (IUGR) pregnancies in order to discriminate if these markers might be involved in progenitor cell functions. Methods: We analyzed 8 samples each of placentae derived from 1 st trimester (elective abortions), and 3 rd trimester IUGR, PE and control (normal term pregnancy placentae). We accomplished immunoperoxidase staining to detect the stem cell markers: CDX2 (trophectoderm SCM), SOX2, NANOG and OCT4A (embryonic SCMs) and NOTCH1 (endothelial SCM) Results: We detected all stem cell markers in all samples of 1 st trimester placentae. The expression all SCMs are homogenous in syncytio- and cytotrophoblast in early pregnancy and grow increasingly mosaic-like towards the end of the 1 st trimester. It appears that the syncytiotrophoblast loses these signals first. These signals are lost or starkly diminished in the 3 rd trimester. Here only singular, apparently cytotrophoblast, cells express these markers. NOTCH1, however, remains highly expressed in all trophoblast subtypes of both IUGR and PE pregnancies. Conclusion: Unexpectedly, both embryonic, as well as trophoblast stem cell markers are expressed in the first trimester trophoblast and appears most vivid among the villous trophoblast of very early pregnancy. Loss of stem cell transcription factor expression in term placentae indicates temporal regulation, and probably a specific function which is yet to be elucidated. Association of the endothelial stem cell marker, NOTCH1, expression with pregnancy pathologies related to endothelial dysfunction underscores the function of this protein, also in the trophoblast population.