MHC-GENOTYPE OF PROGENY INFLUENCED BY PARENTAL INFECTION

In a previous series of in vitro fertilization experiments with mice w e found non-random combination of major histocompatibility complex (MH C) haplotypes in the very early embryos. Our results suggested that tw o selection mechanisms were operating: (i) the eggs selected specific sperm; and (ii) the second meiotic division in the eggs was influenced by the type of sperm that entered the egg. Furthermore, the proportio n of MHC-heterozygous embryos varied over time, suggesting that non-ra ndom fertilization was dependent on an external factor that changed ov er time. As a higher frequency of heterozygous individuals correlated with an uncontrolled epidemic by MHV (mouse hepatitis virus), we sugge sted that MHV-infection might have influenced the outcome of fertiliza tion. Here, we present an experiment that tests this hypothesis. We in fected randomly chosen mice with MHV and sham-infected control mice fi ve days before pairing. We recovered the two-cell embryos from the ovi duct, cultured them until the blastocyst stage, and determined the gen otype of each resulting blastocyst by polymerase chain reaction. We fo und the pattern that we expected from our previous experiments: virus- infected mice produced more MHC-heterozygous embryos than sham-infecte d ones. This suggests that parents are able to promote specific combin ations of MHC-haplotypes during fertilization according to the presenc e or absence of a viral infection.