Inheritance defects of the sperm centrosome in humans and its possible role in male infertility.

During fertilization in humans, the sperm introduces the centrosome, the oocyte's microtubule organizing centre (MTOC), restoring centrosome function. The newly activated oocyte initiates extrusion of the second polar body and begins pronuclear formation. Apposition of the male and female pronuclei requires microtubule-mediated motility in the form of an aster of microtubules emanating from the sperm centrosome. The centrosome then duplicates and separates, forming the two poles of the mitotic spindle, upon which the parental genomes intermix, completing fertilization. The restoration and function of the centrosome is critical for successful fertilization suggesting that a defective sperm centrosome will lead to fertilization arrest and may be a new cause of male infertility. Several types of fertilization failure, associated with the sperm centrosome, are documented. These include: i) failure of the sperm to nucleate microtubules after sperm incorporation; ii) detachment of the sperm centrosome from the sperm head; and iii) failure in microtubule elongation after successful sperm aster formation. Although some types of severe male infertility can be overcome with the use of intracytoplasmic sperm injection (ICSI), men with defective sperm centrosomes are unlikely to benefit. The rate of sperm aster formation, size and organization during bovine fertilization has been used as a measurement of bovine sperm quality. Sperm from bulls which developed large highly organized sperm asters resulted in a higher rate of fertilization in vitro. The development of an assay using Xenopus laevis oocyte extracts has also been used to test centrosome function and sperm aster formation using sperm from men with questionable fertility. In general, these sperm were incapable of forming sperm asters and when used for in vitro fertilization, resulted typically in fertilization failure. These discoveries on the inheritance and function of the sperm centrosome have revealed a new cause of fertilization failure linked to male infertility which may not be circumvented using ICSI.