concanavalin-a and Abortion--Spontaneous

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.

Topics: Abortion, Spontaneous; Animals; Concanavalin A; Diabetes Mellitus, Type 1; Embryo Implantation; Endometrium; Female; Interferon-gamma; Mice; Mice, Inbred BALB C; Mice, Inbred NOD; Mucin-1; Pregnancy; Protein Inhibitors of Activated STAT; Receptors, Progesterone; STAT3 Transcription Factor; Transcription Factor RelA

Avidin-biotin-peroxidase labeling technique was used to localize the binding sites of concanavalin A, peanut agglutinin, and Ulex europaeus in 30 formalin-fixed paraffin-embedded samples of gestational endometrium in intrauterine and ectopic pregnancy, in comparison with 23 samples of normal endometrium at different stages of the menstrual cycle. Concanavalin A shows strong affinity to decidual cells; in normal endometrium its affinity to stroma is weak to moderate. Ulex europaeus, which is weakly positive in normal endometrium, demonstrates focal strong reaction with epithelium and intraluminal secretions in some of the gestational glands. Peanut agglutinin is the most remarkable marker of pregnancy-related changes in endometrium, being strongly positive in the apical portions and intraluminal secretions of the glands; in nonpregnant endometrium its binding capacity is weak.

Topics: Abortion, Spontaneous; Concanavalin A; Endometrium; Female; Humans; Lectins; Menstrual Cycle; Peanut Agglutinin; Plant Lectins; Pregnancy; Pregnancy, Ectopic