Christians Lab
Evolutionary approaches to understanding pregnancy complications
Preeclampsia is a common complication of pregnancy and a leading cause of maternal mortality throughout the world. It results, in part, from reduced invasion of the placenta into the uterine wall. The deep invasion that characterizes our placenta is shared with the other great apes, whereas other primates show shallower invasion. We hypothesized that the evolution of a more invasive placenta involved positive selection on genes crucial to placental development. We tested for positive selection in 18000 genes in the lineage associated with the evolution of increased invasiveness. Genes under positive selection were more likely to have functions relevant to preeclampsia, as predicted. These analyses identified a new candidate gene expected to be required for placental invasion (Crosley et al 2013). In another study, we examined predictions of the predominant theory for the evolution of genomic imprinting, and found that a broad set of imprinted genes is dysregulated in preeclampsia, including some not previously associated with this condition (Christians et al 2017). Placentas from preeclamptic pregnancies often show placental villous hypermaturation (PVH). We found that PVH is associated with improved neonatal outcomes, suggesting that it may be an adaptive, compensatory response to low oxygen (Christians and Grynspan 2019). These studies demonstrate that an evolutionary perspective can inform our mechanistic understanding of pregnancy complications.Relevant papers
Christians JK, Grynspan D (2019) Placental villous hypermaturation is associated with improved neonatal outcomes. Placenta 76: 1-5.Christians, JK, Leavey, K, Cox, BJ (2017) Associations between imprinted gene expression in the placenta, human fetal growth and preeclampsia. Biology Letters 13: 20170643.
Crosley EJ, Elliot MG, Christians JK, Crespi BJ (2013) Placental invasion, preeclampsia risk and adaptive molecular evolution at the origin of the great apes: Evidence from genome-wide analyses. Placenta 34: 127-132.