Evidence against humoral immune attack as the cause of sheep-goat interspecies and hybrid pregnancy failure in the DOE

Abstract

The failure of interspecies and hybrid pregnancies between the domestic sheep (Ovis aries) and goat (Capra hircus) is not completely understood. The sheep-goat hematopoietic chimera is a unique model for studying the role of the maternal immune response in failure of interspecies and hybrid pregnancies between these species. Hematopoietic chimeras were created by in utero transplantation of sheep fetal liver cells into goat fetuses. The resulting chimeric females were recipients of sheep demi-embryos genetically identical to their sheep cells and/or were bred to a ram to create a hybrid pregnancy. Pregnancy sera were analyzed for the presence of anti-species antibodies (Ab) using a lymphocyte microcytotoxicity assay. None of the concepti survived to term. Gross and histological evaluations of two interspecies sheep concepti revealed abnormal placentome formation. The humoral immune response of several hematopoietic chimeras to the challenging concepti differed from control animals. We observed delayed onset of Ab production, low and absent titers, and persistent Ab titers with delayed fetal death. Ultrasonography typically revealed normal fetal development associated with high volumes of placental fluids and retarded placentome development. We conclude that fetal death was associated with abnormal placental development that was not the result of maternal humoral immune attack.