INVESTIGADORES
BARRIENTOS Gabriela Laura
artículos
Título:
Influence of relative NK-DC abundance on placentation and its relation to epigenetic programming in the offspring
Autor/es:
FREITAG, N*; ZWIER, MV*; BARRIENTOS, G; TIRADO-GONZÁLEZ, I; CONRAD, ML; ROSE, M; SCHERJON, SA; PLÖSCH, T; BLOIS, SM
Revista:
Cell Death and Disease
Editorial:
Nature Publishing Group
Referencias:
Lugar: London; Año: 2014 vol. 5
Resumen:
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.(*NF and MVZ contribute equally to this work)