Sperm nuclear activation during fertilization

The delivery of the paternal genome to the egg is a primary goal of fertilization. In preparation for this step, the nucleus of the developing spermatozoon undergoes extensive morphological and biochemical transformations during spermatogenesis to yield a tightly compacted sperm nucleus. These modifications are essentially reversed during fertilization. As a result, the incorporated sperm nucleus undergoes many steps in the egg cytoplasm as it develops into a male pronucleus. The sperm nucleus (1) loses its nuclear envelope, (2) undergoes nucleoprotein remodeling, (3) decondenses and increases in size, (4) becomes more spherical, (5) acquires a new nuclear envelope, and (6) becomes functionally competent to synthesize DNA and RNA. These changes are coordinate with meiotic processing of the maternal chromatin, and often result in behaviors asynchronous with the maternal chromatin. For example, in eggs fertilized during meiosis, the sperm nucleus decondenses while the maternal chromatin remains condensed. A model is presented that suggests some reasons why this puzzling behavior exists. Defects in any of the processes attending male pronuclear development often result in infertility. New assisted reproductive technologies have been developed that ensure delivery of the sperm nucleus to the egg cytoplasm so that a healthy embryo is produced. An emerging challenge is to further characterize the molecular mechanisms that control sperm nuclear transformations and link these to causes of human infertility. Further understanding of this basic process promises to revolutionize our understanding of the mystery of the beginning of new life.