Ultrastructural studies of implantation sites from mice deficient in uterine natural killer cells

Abstract

Implantation sites from three strains of immunodeficient mice [tgepsilon26, IL-2Rbeta nullxp56(lck)null and IL-2Rgamma null, now known as common cytokine chain gamma (gamma(c)) null], which lack uterine natural killer (uNK) cells, are histologically abnormal. The related anomalies (found from day 10 of gestation) include the absence of aggregation of lymphocytes in the mesometrial triangle, acellularity of the mesometrial decidua, decidual arteries with relatively thick walls and reduced lumen diameters, unusual prominence of the endothelium in the major decidual vessels, and an overall reduction in placental size. In this study we have characterized implantation sites in a new mouse strain (gammac(-)/RAG2(-)) that is deficient in all lymphoid lineages. We have compared implantation sites in tgepsilon26 to gammac(-)/RAG2(-)at the ultrastructural level in order to determine the earliest-time point at which implantation sites differed from those in immunocompetent mice, and the cell types affected. Implantation sites from both the uNK cell-deficient mice resemble those from random-bred, immunocompetent mice on days 6 and 7 of gestation. On day 8 of gestation, decidual cells on the mesometrial sides of implantation sites in both tgepsilon26 and gammac(-)/RAG2(-)revealed pleotrophic morphology and degeneration. In some vessels, endothelial cells were distorted or displaced from their supporting cells. Progressive changes, suggestive of loss of function of both the mesometrial decidua and endothelial cells, were seen to day 14 of gestation, the latest time-point analysed. In contrast to tgepsilon26 mice, homozygously-mated gammac(-)/RAG2(-)had normal litter sizes, with birthweights and weaning weights similar to congenic C57Bl/6J controls, and no significant perinatal loss. In both strains, the newly-documented endothelial cell lesions predict detrimental alterations to vasomotor function of the uterine vasculature. These studies add strength to the hypothesis that uNK cells may have specialized physiological, rather than classically immune, functions in the pregnant mammalian uterus.