Characterization of invasive trophoblasts generated from human embryonic stem cells.

Background: Abnormal human embryo implantation leads to poor foetal development and miscarriage, or pre-eclampsia. Ethical and practical considerations concerning implantation limit its investigation, and it is often difficult to extrapolate findings in laboratory animals when implantation processes show diverse species differences. Therefore, it is important to develop new in vitro models to study the earliest events of human implantation.

Telomeric NAP1L4 and OSBPL5 of the KCNQ1 cluster, and the DECORIN gene are not imprinted in human trophoblast stem cells.

Background: Genomic imprinting of the largest known cluster, the Kcnq1/KCNQ1 domain on mChr7/hChr11, displays significant differences between mouse and man. Of the fourteen transcripts in this cluster, imprinting of six is ubiquitous in mice and humans, however, imprinted expression of the other eight transcripts is only found in the mouse placenta. The human orthologues of the latter eight transcripts are biallelically expressed, at least from the first trimester onwards.

ELF5-enforced transcriptional networks define an epigenetically regulated trophoblast stem cell compartment in the human placenta.

The first definitive cell fate decision in development occurs at the blastocyst stage with establishment of the trophoblast and embryonic cell lineages. In the mouse, lineage commitment is achieved by epigenetic regulation of a critical gatekeeper gene, the transcription factor Elf5, that reinforces placental cell fate and is necessary for trophoblast stem (TS) cell self-renewal. In humans, however, the epigenetic lineage boundary seems to be less stringent since human embryonic stem (ES) cells, unlike their murine counterparts, harbour some potential to differentiate into trophoblast derivatives.

Stem cells for reproductive medicine.

The generation of various pluripotent stem cell lines provides a new route to investigate developmental process of germ cell and embryo development, which until now was difficult to access in the human. In the future these cells may be used for new therapies in reproductive medicine. This brief review outlines the development of germ cells and their pluripotent capabilities, how embryonic and germline stem cells can mimic developmental processes in vitro and generate gamete and trophoblast phenotypes for research and potential treatments.