Quo vadis, trophoblast? Exploring the new ways of an old cell lineage

Abstract Trophoblast cells are the first embryonic lineage to differentiate during human development, and are needed to sustain fetal life through their role in constructing a placenta. As the fetus grows, the trophoblast rapidly expands and further differentiates to produce an extravillous subtype that invades the maternal tissues. Some of the extravillous trophoblast cells find their way into the reproductive tract, and can be safely captured by noninvasive collection from the endocervical canal, similarly to a Pap smear. We are developing a new technology for investigating trophoblast cells residing in the cervix to better understand their development, and to glean information from them about pregnancy status. Trophoblast retrieval and isolation from the cervix (TRIC) efficiently isolates hundreds of trophoblast cells without limitations due to early gestational age, maternal obesity, or uteroplacental insufficiency disorders. Cells that appear to be extravillous trophoblast, based on their molecular phenotype, can be purified from Pap smears obtained between 5 and 20 weeks of gestation, using magnetic nanoparticles coupled to an antibody recognizing HLA-G that they specifically produce. Information about fetal genotype and adverse pregnancy outcomes has been obtained using TRIC, and could one day provide assessment of maternal and fetal risk of disease. As perinatal interventions for placental disorders and inherited congenital disorders emerge, TRIC could provide a key diagnostic tool for personalize precision pregnancy management.