The use of primates as models for assisted reproduction

Abstract

Evidence from donated human oocytes and embryos demonstrates that the spermatozoon contributes the ‘centrosome’, which is critical to fertilization, and that some cases of infertility in couples are related to defects in the pathways that reconstitute the zygotic centrosome. A greater understanding of these microtubule-mediated motility events that ensure normal sperm–oocyte interactions has been made easier by the use of non-human primate gametes. Our studies using rhesus monkey gametes have shown that the cytoskeletal events during fertilization by IVF and intracytoplasmic sperm injection (ICSI) are very similar to those of human fertilization, and that manipulations of non-human primate gametes may help to test the safety and improve current strategies for reproduction, as well as develop new techniques. ICSI results in abnormal nuclear remodelling, in part due to the persistence of VAMP (vesicle-associated membrane protein), the acrosome and the perinuclear theca on the sperm head, all of which are normally removed at, or close to, the oocyte cortex during natural and in-vitro fertilization. Progression through the first cell cycle in ICSI oocytes cannot be completed until these structures have been removed from the forming male pronucleus, demonstrating unique differences between ICSI and IVF. While ICSI is of enormous therapeutic value for the treatment of male infertility, fundamental research using clinically relevant animal models is only now unravelling the cellular and molecular events that permit fertilization by sperm microinjection.