title: Severe damage to the placental fetal capillary network causes mid- to late fetal lethality and reduction in placental size in Peg11/Rtl1 KO mice.
abstract: Paternally expressed 11/Retrotransposon-like 1 (Peg11/Rtl1) knockout (KO) mice show mid- to late fetal lethality or late fetal growth retardation associated with frequent neonatal lethality. The lethal phenotype is largely dependent on genetic background and becomes more severe with each succeeding generation in the course of backcross experiments to C57BL/6 (B6). We previously suggested that these lethal and growth phenotypes in the fetal stages were due to severe defects in placental fetal capillaries in the labyrinth layer. In this study, we re-examined KO fetuses and placentas and confirmed that the severe clogging of fetal capillaries was associated with KO fetuses showing mid-fetal lethality with internal bleeding. Importantly, the basal region of the fetal capillary network was specifically damaged, also leading to poor expansion of the labyrinth layer and placental size reduction in the later stage. An apparent down-regulation of transmembrane protein 100 (Tmem100), mesenchyme homeobox 2 (Meox2) and lymphatic vessel endothelial hyaluronan receptor 1 (Lyve1) expression were observed in earlier stage placentas even before apparent size reduction became, suggesting that these genes are involved in the maintenance of fetal capillaries associated with Peg11/Rtl1 during development.
authors.affiliation: Department of Epigenetics, Medical Research Institute, Tokyo Medical and Dental University (TMDU), 1-5-45 Yushima, Bunkyo-ku, Tokyo, 113-8510, Japan.
authors.forename: Moe
authors.initials: M
authors.lastname: Kitazawa
authors.affiliation: Technology and Development Team for Mouse Phenotype Analysis, The Japan Mouse Clinic, RIKEN BioResource Center (BRC), 3-1-1 Koyadai, Tsukuba, Ibaraki, 305-0074, Japan.
authors.forename: Masaru
authors.initials: M
authors.lastname: Tamura
authors.affiliation: School of Health Sciences, Tokai University, 143 Shimokasuya, Isehara, Kanagawa, 259-1193, Japan.
authors.forename: Tomoko
authors.initials: T
authors.lastname: Kaneko-Ishino
authors.affiliation: Department of Epigenetics, Medical Research Institute, Tokyo Medical and Dental University (TMDU), 1-5-45 Yushima, Bunkyo-ku, Tokyo, 113-8510, Japan.
authors.forename: Fumitoshi
authors.initials: F
authors.lastname: Ishino
mesh_terms: D000818:Animals; D002196:Capillaries / Q000378:metabolism / Q000473:pathology; D005260:Female; D005313:Fetal Death; D005317:Fetal Growth Retardation / Q000209:etiology; D008297:Male; D051379:Mice; D018345:Mice, Knockout; D010920:Placenta / Q000033:anatomy & histology / Q000098:blood supply* / Q000378:metabolism; D011247:Pregnancy; D011257:Pregnancy Proteins / Q000172:deficiency / Q000235:genetics* / Q000378:metabolism*
chemical_list: D011257:Pregnancy Proteins; C526773:Rtl1 protein, mouse