and are human placenta-specific imprinted genes associated with germline-inherited maternal DNA methylation.

Genomic imprinting is the parent-of-origin specific monoallelic expression of genes that result from complex epigenetic interactions. It is often achieved by monoallelic 5-methylcytosine, resulting in the formation of differentially methylated regions (DMRs). These show a bias towards oocyte-derived methylation and survive reprogramming in the pre-implantation embryo. Imprinting is widespread in the human placenta. We have recently performed whole-genome screens for novel imprinted placenta-specific germline DMRs (gDMRs) by comparing methylomes of gametes, blastocysts and various somatic tissues, including placenta. We observe that, unlike conventional imprinting, for which methylation at gDMRs is observed in all tissues, placenta-specific imprinting is associated with transient gDMRs, present only in the pre-implantation embryo and extra-embryonic lineages. To expand the list of imprinted genes subject to placenta-specific imprinting, we reinvestigated our list of candidate loci and characterized two novel imprinted genes, and , both of which display polymorphic imprinting. Interrogation of placenta single-cell RNA-seq datasets, as well as cell-type methylation profiles, revealed complex cell-type specificity. We further interrogated their methylation and expression in placental samples from complicated pregnancies, but failed to identify differences between intrauterine growth restricted or pre-eclamptic samples and controls, suggesting they are not involved in these conditions.