title: Influence of relative NK-DC abundance on placentation and its relation to epigenetic programming in the offspring.
abstract: Normal placentation relies on an efficient maternal adaptation to pregnancy. Within the decidua, natural killer (NK) cells and dendritic cells (DC) have a critical role in modulating angiogenesis and decidualization associated with pregnancy. However, the contribution of these immune cells to the placentation process and subsequently fetal development remains largely elusive. Using two different mouse models, we here show that optimal placentation and fetal development is sensitive to disturbances in NK cell relative abundance at the fetal-maternal interface. Depletion of NK cells during early gestation compromises the placentation process by causing alteration in placental function and structure. Embryos derived from NK-depleted dams suffer from intrauterine growth restriction (IUGR), a phenomenon that continued to be evident in the offspring on post-natal day 4. Further, we demonstrate that IUGR was accompanied by an overall reduction of global DNA methylation levels and epigenetic changes in the methylation of specific hepatic gene promoters. Thus, temporary changes within the NK cell pool during early gestation influence placental development and function, subsequently affecting hepatic gene methylation and fetal metabolism.
authors.affiliation: Laboratory of Reproductive Medicine, Medicine University of Berlin, Charité Centre 12 Internal Medicine and Dermatology, Berlin, Germany.
authors.forename: N
authors.initials: N
authors.lastname: Freitag
authors.affiliation: Center for Liver, Department of Pediatrics, University Medical Center Groningen, University of Groningen, Digestive and Metabolic Diseases, Groningen, The Netherlands.
authors.forename: M V
authors.initials: MV
authors.lastname: Zwier
authors.affiliation: Laboratory of Reproductive Medicine, Medicine University of Berlin, Charité Centre 12 Internal Medicine and Dermatology, Berlin, Germany.
authors.forename: G
authors.initials: G
authors.lastname: Barrientos
authors.affiliation: Laboratory of Reproductive Medicine, Medicine University of Berlin, Charité Centre 12 Internal Medicine and Dermatology, Berlin, Germany.
authors.forename: I
authors.initials: I
authors.lastname: Tirado-González
authors.affiliation: Laboratory of Reproductive Medicine, Medicine University of Berlin, Charité Centre 12 Internal Medicine and Dermatology, Berlin, Germany.
authors.forename: M L
authors.initials: ML
authors.lastname: Conrad
authors.affiliation: Laboratory of Reproductive Medicine, Medicine University of Berlin, Charité Centre 12 Internal Medicine and Dermatology, Berlin, Germany.
authors.forename: M
authors.initials: M
authors.lastname: Rose
authors.affiliation: Department of Obstetrics and Gynaecology, University Medical Center Groningen, University of Groningen, Groningen, The Netherlands.
authors.forename: S A
authors.initials: SA
authors.lastname: Scherjon
authors.affiliation: Department of Obstetrics and Gynaecology, University Medical Center Groningen, University of Groningen, Groningen, The Netherlands.
authors.forename: T
authors.initials: T
authors.lastname: Plösch
authors.affiliation: Laboratory of Reproductive Medicine, Medicine University of Berlin, Charité Centre 12 Internal Medicine and Dermatology, Berlin, Germany.
authors.forename: S M
authors.initials: SM
authors.lastname: Blois
mesh_terms: D000818:Animals; D019175:DNA Methylation; D003713:Dendritic Cells / Q000166:cytology* / Q000276:immunology; D044127:Epigenesis, Genetic; D005260:Female; D005317:Fetal Growth Retardation; D066257:Heparin-binding EGF-like Growth Factor / Q000235:genetics / Q000378:metabolism; D007694:Killer Cells, Natural / Q000166:cytology* / Q000276:immunology; D051379:Mice; D008810:Mice, Inbred C57BL; D010920:Placenta / Q000473:pathology; D010929:Placentation; D011247:Pregnancy; D014599:Uterus / Q000473:pathology
chemical_list: D066257:Heparin-binding EGF-like Growth Factor