Paternal contributions to the mammalian zygote: fertilization after sperm-egg fusion

Abstract

Mammalian fertilization has traditionally been regarded as a simple blending of two gametes, during which the haploid genome of the fertilizing spermatozoon constitutes the primary paternal contribution to the resulting embryo. In contrast to this view, new research provides evidence of important cytoplasmic contributions made by the fertilizing spermatozoon to the zygotic makeup, to the organization of preimplantation development, and even reproductive success of new forms of assisted fertilization. The central role of the sperm-contributed centriole in the reconstitution of zygotic centrosome has been established in most mammalian species and is put in contrast with strictly maternal centrosomal inheritance in rodents. The complementary reduction or multiplication of sperm and oocyte organelles during gametogenesis, exemplified by the differences in the biogenesis of centrosome in sperm and oocytes, represents an intriguing mechanism for avoiding their redundancy during early embryogenesis. New studies on perinuclear theca of sperm revealed its importance for both spermatogenesis and fertilization. Remodeling of the sperm chromatin into a male pronucleus is guided by oocyte-produced, reducing peptide glutathione and a number of molecules required for the reconstitution of the functional nuclear envelope and nuclear skeleton. Although some of the sperm structures are transformed into zygotic components, the elimination of others is vital to early stages of embryonic development. Sperm mitochondria, carrying potentially harmful paternal mtDNA, appear to be eliminated by a ubiquitin-dependent mechanism. Other accessory structures of the sperm axoneme, including fibrous sheath, microtubule doublets, outer dense fibers, and the striated columns of connecting piece, are discarded in an orderly fashion. The new methods of assisted fertilization, represented by intracytoplasmic sperm injection and round spermatid injection, bypass multiple steps of natural fertilization by introducing an intact spermatozoon or spermatogenic cell into oocyte cytoplasm. Consequently, the carryover of sperm accessory structures that would normally be eliminated before or during the entry of sperm into oocyte cytoplasm persist therein and may interfere with early embryonic development, thus decreasing the success rate of assisted fertilization and possibly causing severe embryonic anomalies. Similarly, foreign organelles, proteins, messenger RNAs, and mitochondrial DNAs, which may have a profound impact on the embryonic development, are propagated by the nuclear transfer of embryonic blastomeres and somatic cell nuclei. This aspect of assisted fertilization is yet to be explored by a focused effort.