Plac1 (placenta-specific 1) is essential for normal placental and embryonic development

Plac1 is a recently identified, X-linked gene whose expression is restricted primarily to cells of the trophoblast lineage. It localizes to a chromosomal locus previously implicated in placental growth. We therefore sought to determine if Plac1 is necessary for placental and embryonic development by examining a mutant mouse model. Plac1 ablation resulted in placentomegaly and mild intrauterine growth retardation (IUGR). At E16.5, knockout (KO) and heterozygous (Het) placentae of the Plac1-null allele inherited from the mother (X^m-X) weighed approximately 100% more than wildtype (WT) placentae, whereas the corresponding embryos weighed 7-12% less. Histologically, Plac1 mutants exhibited an expanded spongiotrophoblast layer that invaded the labyrinth. By contrast, Het placentae that inherited the null allele from the father (XX^p-) exhibited normal growth and were histologically indistinguishable from WT placentae, consistent with paternal imprinting of Plac1. When examined across gestation, WT and X^m-X placental weights peaked at E16.5 and decreased slightly thereafter. KO placentae (X^m-X^p- and X^m-Y), however, continued to increase in weight after E16.5, consistent with a functional role for the paternal Plac1 allele. Subsequent analysis confirmed that the paternal allele partially escapes complete X-inactivation and thus contributes to placental growth regulation. Additionally, although male Plac1 KO mice can survive, they exhibit decreased viability as a consequence of events occurring late in gestation or shortly after birth. Thus, Plac1 is a paternally imprinted, X-linked gene essential for normal placental and embryonic development.