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.
Seaward
A V C
AV
Department of Anatomy and Cell Biology, Queen's University, Room 915, Botterell Hall, Kingston, ON, Canada.
Burke
S D
SD
Croy
B A
BA
D000818:Animals; D001755:Blastocyst / Q000187:drug effects*; D010064:Embryo Implantation / Q000187:drug effects*; D047108:Embryonic Development / Q000502:physiology*; D005260:Female; D007371:Interferon-gamma / Q000502:physiology*; D008297:Male; D051379:Mice; D016688:Mice, Inbred NOD / Q000502:physiology*; D011247:Pregnancy; D014599:Uterus / Q000098:blood supply
D007371:Interferon-gamma
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