Serious foetal growth restriction is associated with reduced proportions of natural killer cells in decidua basalis

Abstract

Extravillous trophoblasts are major participants in placental development and remodelling of spiral arteries. Trophoblast invasion is regulated by maternal immune cells, and abnormal leucocyte subpopulation composition has been reported in implantation failure. In pre-eclampsia (PE), with or without foetal growth restriction (FGR), superficial trophoblast invasion and insufficient remodelling of spiral arteries are common findings. In the present study, we have compared spiral artery remodelling and leucocyte composition in decidual tissue from 30 cases (PE=8, FGR=5, PE + FGR=17) and 31 controls. Six histological remodelling criteria were established, and each pregnancy obtained a remodelling score. Numbers of natural killer (NK) cells (CD56+), T cells (CD3+) and activated (CD25+ or CD69+) leucocytes were determined and related to total leucocyte (CD45+) numbers in serial sections. Cases demonstrated significantly impaired spiral artery remodelling, inappropriate placental growth and reduced NK cell proportions, as compared to controls (P=0.02, P<0.001 and P=0.01, respectively). Reduced NK cell proportion was primarily found in pregnancies complicated by FGR, with or without PE, and a significant positive correlation was observed between NK cell proportion, trophoblast infiltration and placental growth. Our in vivo observations support the hypothesized association between NK cells, impaired placental development and pathogenesis of PE/FGR.

The Role of Uterine NK Cells in Normal Reproduction and Reproductive Disorders

“…However, in an immunohistochemical study of placental bed biopsies, we demonstrated reduced CD56 + uNK cells in both pre-eclampsia and FGR (Williams et al 2009b ). These results are similar to another report of reduced decidual CD56 + uNK cells in women with severe FGR with and without pre-eclampsia, although there were no differences in pre-eclampsia not associated with FGR (Eide et al 2006 ). A fl ow cytometry study of decidual curettings reported no difference in the proportion of CD45 + cells that were CD56+ CD16-in pre-eclampsia compared with controls, although the proportion of CD45+ cells that were CD56+ CD16+ was reduced in pre-eclampsia (Rieger et al 2009 ).…”

Immune cells in the placental bed

“…However, work in our laboratory demonstrated a reduction in both CD3+ and CD8+ cells in pre-eclampsia (Scaife, Innes, Searle, Robson, Bulmer; unpublished data). This contrasts with Eide et al (2006) who reported no difference in numbers of decidual CD3+ T lymphocytes in women with fetal growth restriction, pre-eclampsia or pre-eclampsia with fetal growth restriction compared to control samples.…”

“…In contrast, in our laboratory we have demonstrated a reduction in CD56+ uNK cells in pre-eclampsia in placental bed biopsies (Scaife, Innes, Searle, Robson, Bulmer; unpublished data). Eide et al (2006) also reported a decrease in decidual CD56+ uNK cell numbers in women with severe fetal growth restriction in the presence or absence of pre-eclampsia, although there were no differences in numbers of decidual CD56+ uNK cells in women with pre-eclampsia alone.…”

The Placenta in Toxicology. Part II

“…These data suggest that proper dNK cell activation is a prerequisite for adequate trophoblast invasion and spiral artery remodeling, and thus a normal placentation. Numerous studies have also addressed the numbers of dNK cells in complications, although the results are inconsistent, for instance, showing reduced, increased, or unchanged dNK cell numbers in preeclampsia and fetal growth restriction (Bachmayer et al 2006;Eide et al 2006;Rieger et al 2009;Sanchez-Rodriguez et al 2011;Wilczynski et al 2003;). …”