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MHC-genotype of progeny influenced by parental infection
T Rülicke1, M Chapuisat, F R Homberger
1Biologisches Zentrallabor, Universitätsspital Zürich, Switzerland.
Abstract:
In a previous series of in vitro fertilization experiments with mice we found non-random combination of major histocompatibility complex (MHC) haplotypes in the very early embryos. Our results suggested that two 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 proportion of MHC-heterozygous embryos varied over time, suggesting that non-random fertilization was dependent on an external factor that changed over time. As a higher frequency of heterozygous individuals correlated with an uncontrolled epidemic by MHV (mouse hepatitis virus), we suggested that MHV-infection might have influenced the outcome of fertilization. Here, we present an experiment that tests this hypothesis. We infected randomly chosen mice with MHV and sham-infected control mice five days before pairing. We recovered the two-cell embryos from the oviduct, cultured them until the blastocyst stage, and determined the genotype of each resulting blastocyst by polymerase chain reaction. We found the pattern that we expected from our previous experiments: virus-infected mice produced more MHC-heterozygous embryos than sham-infected ones. This suggests that parents are able to promote specific combinations of MHC-haplotypes during fertilization according to the presence or absence of a viral infection.
Insights
Mouse hepatitis virus (MHV) infection influences major histocompatibility complex (MHC) haplotype selection during fertilization. Infected mice produced more MHC-heterozygous embryos, suggesting parental control over offspring immunity.
Area of Science:
- Immunogenetics
- Reproductive Biology
- Virology
Background:
- Previous in vitro experiments indicated non-random major histocompatibility complex (MHC) haplotype combinations in early mouse embryos.
- Two selection mechanisms were proposed: egg sperm selection and sperm influence on egg meiosis.
- Embryo MHC heterozygosity varied over time, suggesting an external factor, potentially mouse hepatitis virus (MHV), influenced fertilization.
Purpose of the Study:
- To test the hypothesis that MHV infection influences MHC haplotype selection during fertilization.
- To determine if viral infection affects the non-random combination of MHC haplotypes in early embryos.
Main Methods:
- Randomly chosen mice were infected with MHV or sham-infected as controls five days before mating.
- Two-cell embryos were recovered from oviducts and cultured to the blastocyst stage.
- Blastocyst genotypes were determined using polymerase chain reaction (PCR).
Main Results:
- Virus-infected mice produced a significantly higher proportion of MHC-heterozygous embryos compared to sham-infected controls.
- The observed pattern of MHC heterozygosity aligned with previous experimental findings.
- This indicates a correlation between MHV infection status and non-random MHC haplotype combination.
Conclusions:
- Parental MHV infection promotes the selection of specific MHC-haplotype combinations during fertilization.
- This suggests a parental mechanism to enhance offspring heterozygosity and potentially immune response in the presence of viral infection.
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