HLA-G1/G5 expression throughout human preimplantation development

Successful implantation in the human is dependent on the early
embryo avoiding immune recognition and destruction by the
maternal immune system. Human leukocyte antigen G (HLAG),
a non-classicalHLA class I antigen, is thought to play a key
role in this by modulating cytokine secretion in order to control
trophoblast invasion and to maintain a local immunotolerance.
HLA-G is secreted in culture medium of cleavage stage IVF
embryos but later on in development it is predominantly
expressed in the invasive extravillous trophoblast of the
placenta and in hematopoietic precursors originated from
the extraembryonic yolk sac rather than in the fetus. We
investigated the expression of HLA-G1/G5 in human embryonic
stem cell lines (hESC) and throughout human preimplantation
development by immunocytochemistry with the
monoclonal MEM-G/9 antibody, in order to determine the upand
down-regulation of HLA-G1/G5 in the early embryo.
We detected expression of HLA-G1/G5 in nearly all oocytes,
zygotes, cleavage stage and compacting embryos. At the
blastocyst stage, the first stage at which differentiation into
trophectoderm (TE) and inner cell mass (ICM) is detectable,
HLA-G1/G5 protein was observed in the TE as well as in all the
cells of the ICM. When the blastocyst started to hatch, the TE
and the outer cells of the ICM remained positive whereas the
staining in the inner cells of the ICM disappeared. Because
hESC are undifferentiated pluripotent cells derived from the
ICM of blastocysts, we examined six hESC lines. They all
stained positive for HLA-G1/G5. We can conclude that HLAG1/
G5 is expressed in unfertilized oocytes and throughout
preimplantation development. Since HLA-G1/G5 is expressed
by hESC but not by epiblast cells (inner cells of the differentiated
ICM), we hypothesize that hESC are derived from
earlier undifferentiated ICM cells co-expressing stemness
factors and HLA-G1/G5.