title: 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 therian mammals. In the stem lineage of eutherian mammals, ESF acquired the ability to differentiate into decidual cells in order to allow embryo implantation. We call 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 nondecidualizing neo-ESF). We find evidence for strong stabilizing selection on transcriptome composition suggesting that the expression of approximately 5,600 genes is maintained by natural selection. The evolution of neo-ESF from paleo-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. In the bovine lineage, where invasiveness and decidualization were secondarily lost, we see a re-expression of genes found in 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.
authors.affiliation: Department of Ecology and Evolutionary Biology, Yale University, New Haven, Connecticut Yale Systems Biology Institute, Yale University, West Haven, Connecticut.
authors.forename: Koryu
authors.initials: K
authors.lastname: Kin
authors.affiliation: Yale Systems Biology Institute, Yale University, West Haven, Connecticut.
authors.forename: Jamie
authors.initials: J
authors.lastname: Maziarz
authors.affiliation: Department of Ecology and Evolutionary Biology, Yale University, New Haven, Connecticut Yale Systems Biology Institute, Yale University, West Haven, Connecticut.
authors.forename: Arun R
authors.initials: AR
authors.lastname: Chavan
authors.affiliation: Department of Animal Science, Center for Reproductive Biology and Health, Pennsylvania State University, Stage College, Pennsylvania.
authors.forename: Manasi
authors.initials: M
authors.lastname: Kamat
authors.affiliation: Department of Animal Science, Center for Reproductive Biology and Health, Pennsylvania State University, Stage College, Pennsylvania.
authors.forename: Sreelakshmi
authors.initials: S
authors.lastname: Vasudevan
authors.affiliation: Department of Animal Science, Center for Reproductive Biology and Health, Pennsylvania State University, Stage College, Pennsylvania.
authors.forename: Alyssa
authors.initials: A
authors.lastname: Birt
authors.affiliation: Department of Genetics, Yale School of Medicine, Yale University, New Haven, Connecticut.
authors.forename: Deena
authors.initials: D
authors.lastname: Emera
authors.affiliation: Department of Human Genetics, University of Chicago, Chicago, Illinois.
authors.forename: Vincent J
authors.initials: VJ
authors.lastname: Lynch
authors.affiliation: Department of Animal Science, Center for Reproductive Biology and Health, Pennsylvania State University, Stage College, Pennsylvania.
authors.forename: Troy L
authors.initials: TL
authors.lastname: Ott
authors.affiliation: Department of Pediatrics, Cincinnati Children's Hospital and Medical Center, Cincinnati, Ohio.
authors.forename: Mihaela
authors.initials: M
authors.lastname: Pavlicev
authors.affiliation: Department of Ecology and Evolutionary Biology, Yale University, New Haven, Connecticut Yale Systems Biology Institute, Yale University, West Haven, Connecticut Department of Obstetrics, Gynecology and Reproductive Sciences, Yale Medical School, New Haven, Connecticut Department of Obstetrics and Gynecology, Wayne State University, Detroit, Michigan gunter.wagner@yale.edu.
authors.forename: Günter P
authors.initials: GP
authors.lastname: Wagner
mesh_terms: D000818:Animals; D002417:Cattle; D004717:Endometrium / Q000254:growth & development / Q000378:metabolism*; D004847:Epithelial Cells; D019143:Evolution, Molecular; D005260:Female; D005347:Fibroblasts / Q000378:metabolism; D018507:Gene Expression Regulation, Developmental / Q000235:genetics; D006801:Humans; D008907:Mink / Q000235:genetics; D011247:Pregnancy; D011817:Rabbits; D051381:Rats; D015398:Signal Transduction / Q000235:genetics; D017154:Stromal Cells / Q000378:metabolism*; D059467:Transcriptome / Q000235:genetics*
keywords: Eutheria; Marsupialia; cell type evolution; endometrial stromal cells; transcriptome evolution