Background: The pregnancy pathology preeclampsia is still among the leading causes of
maternal and perinatal morbidity and mortality. At the same time, its etiology is far from being identified
and remains obscure in a number of facets.
A number of hypotheses have been developed to explain the altered interplay between placenta and
mother leading to the clinical symptoms of preeclampsia. However, none of them offers the opportunity
to explain the variability of cases with late-onset versus early-onset, mild versus severe and with
or without additional fetal growth restriction.
Conclusion: This paper identifies the weaknesses of the most important current hypothesis and at the
same time offers a set of new elucidations including maternal susceptibility, and villous/extravillous
trophoblast differentiation to explain the development of preeclampsia. Such elucidations allow following
new scientific routes and pathways to untangle the etiology of preeclampsia.