Human reproduction depends on the fusion of a mature oocyte with a sperm cell to form a fertilized egg. The genetic events that lead to the arrest of human oocyte maturation are unknown. We identified seven mutations in the primate-specific gene TUBB8that were responsible for oocyte meiosis I arrest in 7 of the 24 families. TUBB8 expression is unique to oocytes and the early embryo, in which this gene accounts for almost all the expressed β-tubulin. The mutations affect chaperone-dependent folding and assembly of the α/β-tubulin heterodimer, disrupt microtubule behavior on expression in cultured cells, alter microtubule dynamics in vivo, and cause catastrophic spindle-assembly defects and maturation arrest on expression in mouse and human oocytes. TUBB8 mutations have dominant-negative effects that disrupt microtubule behavior and oocyte meiotic spindle assembly and maturation, causing female infertility. 

Title: Mutations in TUBB8 and Human Oocyte Meiotic Arrest

Links: http://www.nejm.org/doi/full/10.1056/NEJMoa1510791

Editorial comment by Prof. Jurrien Dean:

Title: Exacting Requirements for Development of the Egg

Links: http://www.nejm.org/doi/full/10.1056/NEJMe1515512