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

Stem cells are highly proliferative, undifferentiated cells and stem cell markers are involved in maintaining these characteristics. In the blastocyst, differential expression between embryonic and trophoblast stem cell transcription factors is thought to discriminate cell fate. Although villous cytotrophoblasts are functionally considered a trophoblast stem cell or at least a progenitor cell, which replenishes the outer syncytiotrophoblast layer when necessary, little data is available characterizing the expression of stem cell transcription factors beyond the blastocyst stage. We aimed to describe the expression of trophoblast and embryonal stem cell factors in the placenta between 1st and 3 rd trimester in order to discriminate if these markers might be involved in progenitor cell functions.

Methods: We analyzed 8 each of samples derived from 1st trimester, normal term pregnancy placentae as well as placentae with IUGR and PE. We accomplished immunoperoxidase staining to detect the stem cell markers: Cdx2, Sox2, Notch1, Nanog and Oct4A.

Results: We detected all stem cell markers in all samples of 1st trimester placentae. The expression pattern is homogenous in syncytio- and cytotrophoblast in early pregnancy and grows increasingly mosaic-like towards the end of the 1st trimester. It appears that the syncytiotrophoblast loses the signal first. The signals are lost or starkly diminished in the 3 rd trimester. Here only singular, apparently cytotrophoblast, cells express these markers.

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 stem cell factor expression with reproductive pathologies should constitute the aim of further projects.