Early Cell Lineage Formation in Mammals: Complexity, Species Diversity, and Susceptibility to Disruptions Impacting Embryo Viability

ABSTRACT The emergence of the earliest cell lineages in mammalian embryos is a complex process that utilizes an extensive network of chromatin regulators, transcription factors, cell polarity regulators, and cellular signaling pathways. These factors and pathways operate over a protracted period of time as embryos cleave, undergo compaction, and form blastocysts. The first cell fate specification event separates the pluripotent inner cell mass from the trophectoderm lineage. The second event separates pluripotent epiblast from hypoblast. This review summarizes over 50 years of study of these early lineage forming events, addressing the complexity of the network of interacting molecules, cellular functions and pathways that drive them, interspecies differences, and aspects of these mechanisms that likely underlie their high susceptibility to disruption by numerous environmental factors that can compromise embryo viability, such as maternal health and diet, environmental toxins, and other stressors.