Genomic imprinting in human placentation

Background: Genomic imprinting (GI) is a mammalian-specific epigenetic phenomenon that has been implicated in the evolution of the placenta in mammals. Methods: Embryo transfer procedures and trophoblast stem (TS) cells were used to re-examine mouse placenta-specific GI genes. For the analysis of human GI genes, cytotrophoblast cells isolated from human placental tissues were used. Using human TS cells, the biological roles of human GI genes were examined. Main findings: (1) Many previously identified mouse GI genes were likely to be falsely identified due to contaminating maternal cells. (2) Human placenta-specific GI genes were comprehensively determined, highlighting incomplete erasure of germline DNA methylation in the human placenta. (3) Human TS cells retained normal GI patterns. (4) Complete hydatidiform mole-derived TS cells were characterized by aberrant GI and enhanced trophoblastic proliferation. The maternally expressed imprinted gene p57KIP2 may be responsible for the enhanced proliferation. (5) The primate-specific microRNA cluster on chromosome 19, which is a placenta-specific GI gene, is essential for self-renewal and differentiation of human TS cells. Conclusion: Genomic imprinting plays diverse and important roles in human placentation. Experimental analyses using TS cells suggest that the GI maintenance is necessary for normal placental development in humans.