Who Let the Dogs in: A Canine Trophoblast Invasion Model for Pre-eclampsia

Preeclampsia is a pregnancy-specific syndrome that affects 2-8% of pregnant women worldwide.1 It is the third leading cause of maternal mortality in the United States, accounting for 20% of maternal deaths,2 for which the only known cure is delivery of the placenta.3 Preeclampsia results from abnormal cytotrophoblast invasion of the endometrium and myometrium that morphologically is described as shallow. This superficial trophoblast invasion results in insufficient remodeling of the spiral arteries and hypoperfusion of the human placenta. Despite intensive investigation for more than 50 years;4 the causes of preeclampsia are largely unknown and the effectiveness of current models has been limited. An effective animal model is crucial to understanding the underlying causes of preeclampsia. It is easier and more ethical to obtain placental samples from early gestation in animals. Although preeclampsia can occur in higher apes, it does not occur spontaneously in most non-human primate models studied. Other animal models have struggled to be effective in the study of preeclampsia for a number of reasons. Rodents, such as mice and rats, have been commonly used to study the induction of clinical signs associated with preeclampsia (e.g. high blood pressure, proteinuria) through transgenic and knockout studies, but have proven to be less useful in studying shallow trophoblast invasion.5 To our knowledge, no existing model demonstrates the shallow trophoblast invasion observed in preeclampsia. A larger non-rodent animal model could be more easily manipulated to demonstrate changes in morphology, histochemistry, and gene expression throughout pregnancy. [...]