The first is due to the fact that placental DNA is released into the maternal circulation in all pregnancies as a consequence of placentation. This cell-free DNA can be obtained easily from maternal plasma including the first trimester, originates predominantly from the villus trophoblast, represents the complete fetal genome and permits accurate diagnosis of fetal aneuploidies (trisomy 21, 18 and 13, monosomy X) by maternal plasma DNA sequencing using next-gen sequencing technology. This blood test is safe, can be performed from 10 weeks’ gestation onwards, and has a sensitivity and specificity each above 99% as demonstrated independently by multiple international studies.
The next challenges will be: a. maternal plasma RNA sequencing for presymptomatic transcriptome profiling of the placenta as an early indicator of pregnancies at risk (pre-eclampsia, the HELLP syndrome and intra-uterine growth restriction), b. maternal plasma methyl-C sequencing to determine the placental epigenotype
The second is due to the fact that the placental (epi)genotype determines the maternal phenotype when the fetal susceptibility allele by being expressed by the extravillus trophoblast leads to failure of the process of spiral artery vessel wall modification. This etiological defect in trophoblast dysfunction triggers a cascade of placental dysfunction, and maternal (de)compensation that ultimately -by a maternal defect in vasomotor control-leads to clinical symptoms, i.e. new onset hypertension and proteinuria. In early onset pre-eclampsia associated with IUGR and a grandmaternal origin, the epigenotype of the STOX1 gene coding for a transcription factor related to the Forkhead multigene family plays an essential role in the inverse relation between cell cycle exit and invasion of the extravillus trophoblast. Additional data indicate the involvement of paralogous genes, i.e. STOX2, in pre-eclampsia and a novel large non coding RNA in the HELLP syndrome.