Circulating CD56+ cells of diabetic women show deviated homing potential for specific tissues during and following pregnancy.

BACKGROUND: Human uterine natural killer (uNK) cells, the dominant lymphocytes in early pregnancy decidua, are important for spiral arterial remodelling. uNK cells are thought to arise from circulating CD56(bright) NK cells that egress into decidualizing endometrium. Both incomplete spiral arterial modification and aberrant NK cell function have been linked with pre-eclampsia, a syndrome that is more prevalent in diabetic women. Since previous in vitro studies have shown that changes in decidual endothelium induced by type 1 diabetes (T1D) reduce its interactions with circulating leucocytes, we hypothesized that diabetes additionally has direct effects on circulating CD56(+) NK cells that impair their decidual homing potential. METHODS: Serial blood samples were collected from control, T1D and T2D pregnant women throughout and after pregnancy. In vitro adhesion under shear forces was used to assay the functional capacity of circulating leucocytes and of CD56(+) cells to adhere to endothelium in cryostat sections of gestation day (gd) 7 normal mouse decidua, pancreas and lymph node. RESULTS: Fewer CD56(+) cells from diabetic compared with control women adhered to normal decidual endothelium. The CD56(+) cell/total cell adhesion ratio was also lower in diabetics. More diabetic CD56(+) cells adhered to pancreatic endothelium and their proportion was greater than for controls. Neither absolute nor proportional adhesion of CD56(+) cells to lymph node endothelium differed between diabetics and controls. CONCLUSIONS: The CD56(+) cell adhesion patterns of T1D and T2D women differ from those of non-diabetic women and support the hypothesis that diabetes impairs mechanisms that could be used by CD56(+) cells for egress into decidua.

Interferon gamma contributes to preimplantation embryonic development and to implantation site structure in NOD mice.

BACKGROUND: Pre-eclampsia, a syndrome usually accompanied by incomplete spiral arterial modification, occurs at an increased frequency in diabetic women. Hyperglycemia in non-obese type 1 diabetic (NOD) mice impairs gestational spiral arterial remodeling despite high local levels of interferon gamma (Ifng), the triggering cytokine in mice. Pregnancies in NOD.Ifng(-/-) mice were assessed to investigate this issue. METHODS: Fecundity was assessed using the breeding history, flushing of preimplantation embryos and histological and morphometric studies of implantation sites in normoglycemic (n-) and hyperglycemic (d-) females of NOD.Ifng(-/-) and NOD genotypes. RESULTS: NOD.Ifng(-/-) but not NOD mice are mostly infertile. In NOD.Ifng(-/-), copulation often does not result in a post-implantation pregnancy. Defective fertilization and delayed preimplantation development limit n-NOD.Ifng(-/-) fertility, and both mechanisms are exacerbated by hyperglycemia. At mid-gestation, implantation sites in n-NOD.Ifng(-/-) and n-NOD mice are histologically similar. However, in d-NOD.Ifng(-/-), there is minimal development of spiral arteries, hypertrophy of the myometrial region containing uterine Natural Killer (uNK) cells and a deficit in cytoplasmic granule formation in the uNK cells. CONCLUSIONS: Ifng contributes to the success of fertilization and to the rate of preimplantation mouse embryo development in normogylcemic and hyperglycemic pregnancies. A physiological role for this cytokine in human preimplantation development merits investigation.