CITED2 is a Conserved Regulator of the Uterine-Placental Interface

• Published in: bioRxiv
• Main Authors: Kuna, Marija, Dhakal, Pramod, Iqbal, Khursheed, Dominguez, Esteban M, Kent, Lindsey N, Muto, Masanaga, Moreno-Irusta, Ayelen, Kozai, Keisuke, Varberg, Kaela M, Okae, Hiroaki, Arima, Takahiro, Sucov, Henry M, Soares, Michael J
• Format: Paper
• Language: English; Japanese
• Published: Cold Spring Harbor Cold Spring Harbor Laboratory Press 23.11.2022
• Subjects: Aspartic acid; Cell lineage; CITED2 gene; Fetuses; Gene deletion; Glutamic acid; Placenta; Uterus
• DOI: 10.1101/2022.06.15.496287

Establishment of the hemochorial uterine-placental interface requires exodus of trophoblast cells from the placenta and their transformative actions on the uterus, which represent processes critical for a successful pregnancy, but are poorly understood. We examined the involvement of CBP/p300-interacting transactivator with glutamic acid/aspartic acid-rich carboxyl terminal domain 2 (CITED2) in rat and human trophoblast cell development. The rat and human exhibit deep hemochorial placentation. CITED2 was distinctively expressed in the junctional zone and invasive trophoblast cells of the rat. Homozygous Cited2 gene deletion resulted in placental and fetal growth restriction. Small Cited2 null placentas were characterized by disruptions in the junctional zone, delays in intrauterine trophoblast cell invasion, and compromised plasticity. In the human placentation site, CITED2 was uniquely expressed in the extravillous trophoblast (EVT) cell column and importantly contributed to development of the EVT cell lineage. We conclude that CITED2 is a conserved regulator of deep hemochorial placentation.Competing Interest StatementThe authors have declared no competing interest.Footnotes* Figure 6 has been updated to include new in situ hybridization and invasion assay. Supporting Figure S4 and S9 has been added, and S7 updated.