https://pubmed.ncbi.nlm.nih.gov/42007670/

Placenta enriched 1 (PLAC1) is a highly conserved X chromosome-linked gene prominently expressed in the mammalian placenta. The functions of PLAC1 in placentation have yet to emerge fully. The rat shares hemochorial placentation and deep intrauterine trophoblast cell invasion with the human. Herein, we investigated the expression and biological activities of PLAC1 in the rat and human placenta. Plac1 transcripts were prominently expressed in the junctional zone of the rat placenta, a structure analogous to the extravillous trophoblast cell column of the human placentation site, and in invasive trophoblast cells. A PLAC1 mutant rat model was generated using CRISPR/Cas9 genome editing and used to investigate the role of PLAC1 in rat placentation. Plac1 mutant animals exhibited placentomegaly. Enlarged placentas were characterized by an expanded junctional zone, an irregular junctional zone-labyrinth zone boundary, and a prominent depletion of invasive trophoblast cells within the uterine parenchyma. PLAC1 was required for rat trophoblast stem (TS) cell differentiation. In human TS cell development, PLAC1 does not contribute to the regulation of the human invasive/extravillous trophoblast cell lineage, but instead, PLAC1 expression and actions were linked to syncytiotrophoblast differentiation. Thus, PLAC1 is critically involved in hemochorial placentation; however, the responsive trophoblast cell lineages and its contributions to placentation are fundamentally distinct in the rat versus human.