title: Endometrial receptivity defects and impaired implantation in diabetic NOD mice.
abstract: Implantation failure is a major hurdle to a successful pregnancy. The high rate of postimplantation fetal loss in nonobese diabetic (NOD) mice is believed to be related to an abnormal decidual production of interferon (IFN)gamma. To address whether diabetes alters the natural events associated with successful implantation, certain morphological and molecular features of uterine receptivity in diabetic NOD (dNOD) mice were examined in normally mated pregnancy and in concanavalin A (ConA)-induced pseudopregnancy. As opposed to normoglycemic NOD (cNOD) mice, dNOD mice expressed retarded maturation of their uterine pinopodes and overexpressed MUC1 mucin at implantation sites (P < 0.001). Uterine production of leukemia inhibitory factor (LIF) and phosphorylation of uterine NFkappaBp65 and STAT3-Ty705 were found to be low (P < 0.01) during Day 4.5 postcoitum, whereas IFNgamma was aberrantly overexpressed. Loss of temporal regulation of progesterone receptor A (PR A) and PR B, together with aberrantly increased expression of the protein inhibitor of activated STAT-y (PIASy) (P < 0.01) and reduced recruitment (P < 0.01) of the latter to nuclear progesterone receptor sites were prominent features of decidualization failure occurring at peri-implantation in dNOD mice. In conclusion, the aberrant expression of endometrial IFNgamma in dNOD mice is associated with a nonreceptive endometrial milieu contributing to peri-implantation embryo loss in type 1 diabetes.
authors.affiliation: Department of Biomedical and Molecular Sciences, Queen's University, Kingston, Ontario, Canada.
authors.forename: Ahmad J H
authors.initials: AJ
authors.lastname: Albaghdadi
authors.forename: Frederick W K
authors.initials: FW
authors.lastname: Kan
mesh_terms: D000022:Abortion, Spontaneous / Q000209:etiology* / Q000378:metabolism; D000818:Animals; D003208:Concanavalin A; D003922:Diabetes Mellitus, Type 1 / Q000150:complications* / Q000378:metabolism; D010064:Embryo Implantation; D004717:Endometrium / Q000378:metabolism* / Q000648:ultrastructure; D005260:Female; D007371:Interferon-gamma / Q000378:metabolism; D051379:Mice; D008807:Mice, Inbred BALB C; D016688:Mice, Inbred NOD; D018396:Mucin-1 / Q000378:metabolism*; D011247:Pregnancy; D050828:Protein Inhibitors of Activated STAT / Q000378:metabolism; D011980:Receptors, Progesterone / Q000378:metabolism; D050796:STAT3 Transcription Factor / Q000378:metabolism; D051996:Transcription Factor RelA / Q000378:metabolism
chemical_list: D018396:Mucin-1; C414349:Piasy protein, mouse; D050828:Protein Inhibitors of Activated STAT; D011980:Receptors, Progesterone; C498144:Rela protein, mouse; D050796:STAT3 Transcription Factor; C494087:Stat3 protein, mouse; D051996:Transcription Factor RelA; D003208:Concanavalin A; D007371:Interferon-gamma