Molecular mechanisms of trophoblast survival: From implantation to birth

Abstract

Fetal development depends upon a coordinated series of events in both the embryo and in the supporting placenta. The initial event in placentation is appropriate lineage allocation of stem cells followed by the formation of a spheroidal trophoblastic shell surrounding the embryo, facilitating implantation into the uterine stroma and exclusion of oxygenated maternal blood. In mammals, cellular proliferation, differentiation, and death accompany early placental development. Programmed cell death is a critical driving force behind organ sculpturing and eliminating abnormal, misplaced, nonfunctional, or harmful cells in the embryo proper, although very little is known about its physiological function during placental development. This review summarizes current knowledge of the cell death patterns and molecular pathways governing the survival of cells within the blastocyst, with a focus on the trophoblast lineage prior to and after implantation. Particular emphasis is given to human placental development in the context of normal and pathological conditions. As molecular pathways in humans are poorly elucidated, we have also included an overview of pertinent genetic animal models displaying defects in trophoblast survival.

Vital Role of the Calpain-Calpastatin System for Placental-Integrity-Dependent Embryonic Survival

“…Indeed, preeclampsia, a disease of human pregnancy, seems to be associated with cell death in the placenta (8,19,30). Despite the fact that a substantial number of human pregnancies fail as spontaneous abortions after implantation, the underlying mechanisms remain undetermined.…”

Cell-Cell Fusion Induced by Measles Virus Amplifies the Type I Interferon Response

“…Notable exceptions are the fusion of cellular precursors undergoing a specific maturation process, such as myotubes, osteoclasts, and syncytiotrophoblasts. In the two latter cases, a survival program is turned on (15,31). Whether such a mechanism occurs for the survival of MeV-induced MGC remains to be determined.…”

Diminished survival of human cytotrophoblast cells exposed to hypoxia/reoxygenation injury and associated reduction of heparin-binding epidermal growth factor-like growth factor

“…HTR-8/SVneo cell proliferation increases at 2% O 2 (12,13) as in primary cultured cytotrophoblast and villous explants under similar O 2 conditions (30,31). The inhibition of HBEGF secretion or its binding to HER 1 and HER 4 during exposure to 2% O 2 did not prevent the increase in cell proliferation (12).…”