title: Fematrin-1 is involved in fetomaternal cell-to-cell fusion in Bovinae placenta and has contributed to diversity of ruminant placentation.
abstract: During placentation, mammals employ different strategies for nourishing and supporting fetuses. Members of the Bovidae family, consisting of cloven-hoofed ruminants, utilize multiple maternal attachment points on the placenta, known as cotyledons, and hybrid cells, named trinucleate cells or syncytial plaques, made up of a fusion of fetal trophoblasts and maternal endometrial cells to provide essential hormones and maintain long gestation periods. These hybrid cells are unique to the Bovidae, as fetomaternal borders are clearly separated by syncytiotrophoblasts or epithelial cells in the placenta of other mammals. Recently, it was reported that Syncytin-Rum1 was inserted into ruminant genomes, including cattle and sheep, and was possibly involved in fetomaternal cell-to-cell fusion in both species. However, Syncytin-Rum1 alone is insufficient to explain the morphological diversity of the fetomaternal hybrids between Bovinae and Caprinae (i.e., trinucleate cells in Bovinae and syncytial plaques in Caprinae). Here we report that the bovine endogenous retrovirus K1 (BERV-K1) envelope, which we term Fematrin-1, was specifically expressed in binucleated trophoblasts throughout gestation in cattle and induced fusion with bovine endometrial cells in vitro at a significantly higher level than Syncytin-Rum1 under physiological conditions. Fematrin-1 was found to be integrated into intron 18 of FAT tumor suppressor homolog 2 (FAT2) about 18.3 to 25.4 million years ago and has been subject to purifying selection through the evolution of Bovinae. Phylogenetically, Fematrin-1 is distinct from Syncytin genes found in other mammalian species that form syncytiotrophoblasts. Our results suggest that the newly acquired endogenous retroelement has contributed to generating placentation diversity through ruminant evolution.
authors.affiliation: Laboratory of Signal Transduction, Department of Cell Biology, Institute for Virus Research, Kyoto University, Kyoto, Japan.
authors.forename: Yuki
authors.initials: Y
authors.lastname: Nakaya
authors.forename: Katsuo
authors.initials: K
authors.lastname: Koshi
authors.forename: So
authors.initials: S
authors.lastname: Nakagawa
authors.forename: Kazuyoshi
authors.initials: K
authors.lastname: Hashizume
authors.forename: Takayuki
authors.initials: T
authors.lastname: Miyazawa
mesh_terms: D000818:Animals; D005075:Biological Evolution; D015153:Blotting, Western; D002417:Cattle; D002459:Cell Fusion; D002478:Cells, Cultured; D020077:Endogenous Retroviruses / Q000502:physiology*; D004717:Endometrium / Q000378:metabolism; D005260:Female; D015686:Gene Products, env / Q000235:genetics / Q000378:metabolism; D015151:Immunoblotting; D007124:Immunoenzyme Techniques; D017403:In Situ Hybridization; D008431:Maternal-Fetal Exchange; D010802:Phylogeny; D010920:Placenta / Q000166:cytology / Q000378:metabolism*; D010929:Placentation / Q000502:physiology*; D011247:Pregnancy; D011257:Pregnancy Proteins / Q000235:genetics / Q000378:metabolism; D012333:RNA, Messenger / Q000235:genetics; D060888:Real-Time Polymerase Chain Reaction; D012192:Retroviridae Infections / Q000378:metabolism / Q000821:virology; D020133:Reverse Transcriptase Polymerase Chain Reaction; D012418:Ruminants / Q000502:physiology*; D014327:Trophoblasts / Q000166:cytology / Q000378:metabolism / Q000821:virology; D014412:Tumor Virus Infections / Q000378:metabolism / Q000821:virology; D014759:Viral Envelope Proteins / Q000235:genetics*
chemical_list: D015686:Gene Products, env; D011257:Pregnancy Proteins; D012333:RNA, Messenger; D014759:Viral Envelope Proteins; C405335:syncytin