Prenatal HgCl(2) Exposure Alters Fetal Cell Phenotypes

Here we sought to determine whether prenatal exposure to subtoxic levels of inorganic mercury induced modulations in the fetal immune repertoire. After overnight breeding of female BALB/c and male DBA/1 mice, pregnant females were exposed to 10 mg/l mercuric chloride in drinking water. DBF(1) pups were examined at day 16 of gestation for immunophenotypic changes in the fetal thymus and liver. While total thymocyte counts remained comparable to unexposed controls, intrauterine mercury exposure was found to modulate several immune phenotypes in the fetal thymus. Specifically, we saw an increase in the percentages of double negative (DN, CD4(-)CD8(-)) cells as well as a reduction in the numbers of cells representing activation phenotypes (CD4(+)CD25(+)). In the liver, we observed modulations that suggested skewing of the development of B220(+)-expressing cells with mercury exposure. Further, we saw increased populations of thymic and splenic lymphocytes reactive with a pathogenic idiotypic determinant Id(LN)F(1,) which is associated with spontaneous autoimmune nephritis in (NZB x SWR)F(1) (SNF(1)) mice. Previous studies from our laboratory have shown that dysregulation of the Id(LN)F(1) idiotypic network, particularly the expansion of idiotype-reactive T- and B-lymphocytes, is key in the development of lupus nephritis in the autoimmune SNF(1) mouse. These studies show that acute exposure to relatively low levels of inorganic mercury in utero may alter the fetal immune repertoire which could potentially modulate post-natal immune responses.