Molecular and biochemical regulation of early mammalian development

Fertilization initiates a rapid series of changes that restructures the egg into the zygote and initiates the program of early development. These changes in the cell occur while the genetic complement of the egg and sperm are in a highly condensed state and unable to participate in transcription. The egg cytoplasm, formed by the maternal genome, contains the necessary components that mediate the early restructuring of egg into zygote. These changes are mediated by a series of cytoplasmic signal transduction events initiated by the rise in [Ca²⁺]_i caused when the sperm penetrates the egg. The structural changes that the egg undergoes are rapid and result in the extensive remodeling of this specialized cell. Protein kinase C (PKC) and calcium/calmodulin-dependent protein kinase II (CaM KII) are two pivotal signaling agents that mediate several of these rapid modifications in cell structure. Studies indicate the meiotic spindle serves as an architectural element in the egg that acts to colocalize elements from several of the key signaling pathways and may provide a means for these pathways to interact. In mammals, transcription begins earlier than in zygotes from other classes of organisms, starting several hours after fertilization in the male and female pronuclei and continuing in the embryonic nuclei. Studies indicate that nuclei undergo an initial state that is permissive for transcription, and then in Gap 2 of the two-cell embryo, enter a transcriptionally repressive state. These changes have been linked to the times during the cell cycle when the DNA is replicated, and also have been proposed as a requirement for proper initiation of the program of early development.