THE MOLECULAR DISSECTION AND RECONSTITUTION OF THE CENTROSOME DURING HUMAN FERTILIZATION - IMPLICATIONS FOR INFERTILITY

Successful fertilisation is concluded when the parental chromosomes in termix at metaphase of first mitosis and this requires both centrosome restoration and microtubule-mediated motility. Recent discoveries hav e shown that humans inherit their centrosomes from their fathers in a manner consistent with all other mammals except rodents. Microtubule a nd DNA imaging of inseminated human zygotes demonstrates that the intr oduced sperm centrosome nucleates new microtubule assembly required fo r effecting genomic union - steps essential for successful fertilisati on. Defects in the pathways which reconstitute the centrosome followin g fertilisation or in the organisation of the microtubules which unite the egg and sperm nuclei are involved in some cases of human infertil ity and are not resolved by reproductive techniques such as intracytop lasmic sperm injection (ICSI). These observations are reinforced by ex amining the microtubule and DNA patterns in the non-human primate, the rhesus monkey, after normal or ICSI fertilisation. This article revie ws our current knowledge of centrosome inheritance in primates and all udes to defects in centrosomal constituents which may cause novel form s of male infertility. An analysis of the molecular dissection and rec onstitution of the human sperm centrosome in vitro will be presented a nd speculation on molecular medical approaches will be discussed, whic h may have important implications for infertility diagnosis and managi ng reproduction.