Fundamental and unique roles of PLAC1 in the regulation of rat and human trophoblast cell development.

Placenta enriched 1 (PLAC1) is a conserved X chromosome-linked gene expressed in the mammalian placenta. We investigated the biology of PLAC1 in the rat and human placenta. Plac1 transcripts were expressed in the junctional zone of the rat placenta and in intrauterine invasive trophoblast cells. Genome-edited Plac1 mutant animals exhibited placentomegaly. Enlarged placentas were characterized by an expanded junctional zone, an irregular junctional zone-labyrinth zone boundary, a deficiency of intrauterine invasive trophoblast cells, and a late-gestation-stage uterine-placental interface infiltrated with natural killer cells. PLAC1 facilitated rat trophoblast cell differentiation. In contrast, PLAC1 showed minimal contributions to the regulation of the human invasive/extravillous trophoblast cell lineage, but instead PLAC1 expression and actions were linked to syncytiotrophoblast differentiation. Furthermore, the impact of PLAC1 on cellular function is linked to furin (paired basic amino acid cleaving enzyme) in rat and human trophoblast cells. Thus, PLAC1 plays an important role in hemochorial placentation; however, the responsive trophoblast cell lineages and its contributions to placentation are fundamentally distinct in the rat versus human.