ImmunogeJ~eticsI8: 131-135, 1983 Imm/ o_ genetics © Springer-Verlag 1983 H-2 Haplotype and the Embryotoxicity of Serum from Nonpregnant Congenic Mice Michael Melnick, Tina Jaskoll, and Mary Marazita Laboratory for Developmental Biology, AndrusGerontology Center,University of SouthernCalifornia, Los Angeles,California90089 Abstract. Previous studies revealed a significant association between genes at or near the H-2 complex and fetal loss. Reasoning that the maternal serum might contain one or more unknown factors that are harmful to early embryonic or fetal development, or both, we performed an embryotoxicity screen using chick embryos and serum from nonpregnant C57BL/lOSn(H-2 b) and B10.A/SnSg (H-2 ~) congenic mice. Serum from the strain with the higher frequency of fetal loss (C57BL/10 Sn) yielded a significantly greater frequency of chick abnor- mality, specifically neural tube malformation and death, than the serum from the strain with the lower frequency of fetal loss (B 10.A/SnSg). Further, the C57BL/10 Sn serum demonstrated a highly significant dose-response. These results suggest that analogous studies may be profitable with women who have a history of chronic fetal wastage and/or offspring with neural tube defects. Introduction Roberts and Lowe (1975) have estimated that as many as 80% of all human conceptions are aborted prior to term. Certainly, a substantial proportion of these have abnormalities that are clearly associated with mutant genes, chromosome abnormalities, or exogenous environmental factors; however, the remainder is presently unexplained and might presumably be attributed to endogenous maternal factors such as genotype or uterine environment (Heap et al. 1979). Using congenic strains of mice as a model, we (Melnick et al. 1981) investigated the possible association of H-2 haplotype with the frequency of fetal loss. The results of that study revealed a significant association between genes at or near the H-2 complex and fetal loss. For example, C57BL/10Sn (H-2 b) mice had significantly (P < 0.001) greater fetal loss than B 10.A/SnSg (H-2 a) mice. In summary, the data suggested that particular allelic variants at or near the H-2 complex confer some selective advantage as measured by differential fetal survival.