Trophoblast differentiation in the bovine placenta

Cattle have a synepitheliochorial type of placenta characterized as semi-invasive with distinctive placentomes that develop from interdigitation and growth of placental cotyledons and endometrial caruncles that are crucial for fetal growth and development. As the elongated bovine conceptus begins implantation, trophoblast giant cells (TGC), also referred to as binucleate trophoblast cells, begin to differentiate from progenitor uninucleate cells (UNC). Based primarily on histological studies, the TGC developmental program is theorized to involve endoreplication of progenitor UNC to produce polyploid TGC. TGC are highly specialized cells with unique gene regulatory networks that enable production of pregnancy-specific proteins, such as chorionic somatomammotropin hormone 2 (CSH2; also known as placental lactogen), pregnancy-associated glycoproteins (PAGs), and prolactin-related proteins (PRPs). Secreted factors from the TGC impact uterine gland development and secretory function, fetal growth and development, and maternal adaptations to pregnancy. Importantly, TGC are part of the foundation of cotyledons required for placentome formation. Single cell atlases of the developing and mature bovine placenta and derivation of trophoblast stem cells (TSC) and their differentiation into UNC and TGC are new developments in the field. This review will discuss how those advances impact our fundamental knowledge of trophoblast differentiation and placenta development in cattle.