The transcriptomic evolution of mammalian pregnancy:gene expression innovations in endometrial stromal fibroblasts

Abstract

The endometrial stromal fibroblast (ESF) is a cell type present in the uterine lining of therianmammals. In the stemlineage of eutherian mammals, ESF acquired the ability to differentiate into decidual cells in order to allow embryo implantation.Wecall the latter cell type "neo-ESF" in contrast to "paleo-ESF"which is homologous to eutherian ESF but is not able to decidualize. In this study, we compare the transcriptomes of ESF from six therian species: Opossum (Monodelphis domestica; paleo-ESF), mink, rat, rabbit, human (all neo- ESF), and cow(secondarily nondecidualizingneo-ESF).Wefindevidence for strong stabilizingselectionontranscriptome composition suggesting that the expression of approximately 5,600 genes ismaintainedby natural selection. The evolution of neo-ESF frompaleo- ESF involved the following gene expression changes: Loss of expression of genes related to inflammation and immune response, lower expression of genes opposing tissue invasion, increased markers for proliferation as well as the recruitment of FOXM1, a key gene transiently expressed during decidualization. Signaling pathways also evolve rapidly and continue to evolve within eutherian lineages. Inthe bovine lineage, where invasiveness anddecidualizationwere secondarily lost,we see a re-expressionofgenes foundin opossum, most prominently WISP2, and a loss of gene expression related to angiogenesis. The data from this and previous studies support a scenario,where the proinflammatory paleo-ESF was reprogrammed to express anti-inflammatory genes in response to the inflammatory stimulus coming from the implanting conceptus and thus paving the way for extended, trans-cyclic gestation.