276 POSSIBLE MECHANISM FOR NON-REJECTION OF THE DEVELOP-2/6 ING MAMMALIAN EMBRYO: THE ROLES OF UTEROGLOBULIN AND TRANSGLUTAMINASE

Abstract

The suppression of embryonic immunogenicity by the interaction of rabbit blastocysts with uteroglobin (UG) (a pregnancy specific protein) and transglutaminase (TG) (Factor XIIIa) has been investigated in vitro. When incubated with maternal lymphocytes, washed, mitomycin-C inactivated blastomeres stimulated lymphocyte 3H-thymidine incorporation (1.23 × 105 cpm/2 × 106 lymphocytes), suggesting recognition of embryonic antigens. When these blastomeres are pretreated with pregnant uterine flushings (PUF), 3H-thymidine incorporation was dramatically reduced (1.0 × 104 cpm/2 × 106 lymphocytes). Pretreatment of blastomeres with UG alone, isolated to homogeneity from PUF, or in combination with TG caused significant dose dependent suppression of thymidine incorporation by the lymphocytes. Suppression to <100 cpm/2 × 106 cells was achieved by 250 ug/ml of UG alone; with added TG (3 u/ml) only 1.0 ug/ml of UG caused total suppression. Suppression was blocked by incubation of UG with its antiserum, or with TG plus anti-TG, prior to blastomere pretreatment. Inhibition of exogenous transglutaminase by neopentyl chloroethyl nitrosourea also greatly reduced the inhibition of thymidine incorporation by UG. The data clearly indicate that UG and TG suppress blastomere immunogenicity, perhaps by a cross-linking mechanism between UG and blastomere antigens. We suggest that uteroglobin in conjunction with transglutaminase may inhibit immunorejection of embryos at about the time of implantation.