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

Abstract

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. 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. 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. 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.