Fetal influence on maternal pregnancy through the Peg3 imprinted domain

Abstract

Genomic imprinting plays critical roles in the reproduction of mammalian species. In this study, potential roles of the Peg3 imprinted domain in mammalian reproduction were analyzed with the mutant mouse model lacking the oocyte-specific alternative promoter U1, which exhibits the abnormal biallelic expression or 2x gene dosage of Peg3. According to the results, the pregnant females displayed several mutant phenotypes related to reproduction, including delayed parturition, and defects in placentophagy and nest-building behaviors, causing subsequent neonatal lethality. These phenotypes were observed from the homozygote females delivering the entire litter with 2x Peg3, but not from the heterozygotes producing a half of litter with 2x Peg3, suggesting the presence of maximal tolerable gene dosage of Peg3 for healthy pregnancy as well as potential fetal influence on maternal pregnancy through the gene dosage of the Peg3 domain. Detailed analyses also revealed partial embryonic lethality among the female with 2x Peg3, suggesting the susceptibility of the female to the elevated gene dosage of Peg3. Overall, this highlights that the gene dosage of the Peg3 domain is critical for the successful mammalian reproduction.