Does genome organization matter in spermatozoa? A refined hypothesis to awaken the silent vessel

The spermatozoon is considered by many to be a silent vessel whose only function is to safely deliver the paternal genome to the maternal oocyte. As a result, the paternal contribution to fertilization and embryogenesis is frequently overlooked. However, the spermatozoon is a highly elaborate and specialized cell that is formed through the process of spermatogenesis. Spermatogenesis is a complex cellular program of differentiation that produces mature spermatozoa, which are essential for reproduction, fertilization, and normal embryonic development. The sperm cell is unique in morphology, chromatin structure, and function. Increasing evidence demonstrates that perturbations in chromatin integrity and organization could have a significant clinical impact on fertilization and embryogenesis. In this article we will review the evidence that demonstrates the paternal genome to be highly packaged and uniquely organized. We will postulate how the integrity and organization of the paternal genome likely has functional consequences that are critical for the establishment and maintenance of a viable pregnancy. In doing so, we hope to dispel the common myth that the sperm cell is a silent vessel; instead we will demonstrate the sperm cell to be a highly segmentally organized, epigenetically primed cell. Abbreviations: 2D: two-dimension; 3C: chromosome conformation capture; 3D: three-dimension; 4D: four-dimension; CTs: chromosome territories; FISH: fluorescence in situ hybridization; IMSI: intra cytoplasmic morphologically selected sperm injection; ICSI: intracytoplasmic sperm injection; IVF: in-vitro fertilization; mESCs: mouse embryonic stem cells; NORs: nuclear organizing regions; TADs: topologically associated domain.