An investigation into a meiotic checkpoint that monitors sex chromosome pairing.

There is extensive evidence for the existence of a meiotic "quality control" that acts to eliminate those germ cells which fail to achieve full sex chromosome synapsis at the pachytene stage of the first meiotic prophase. A study was undertaken of the role this meiotic checkpoint in a number of cases of sex chromosomally induced spermatogenic arrest in mice. XYY mice are sterile, and sex chromosome pairing anomalies and the double Y gene dosage, have both been implicated as the cause of sterility. Meiosis in mice with three sex chromosomes but only one dose of Y specific DNA (XYY*X) was compared to that of XYY mice. It was determined that failure of sex chromosome synapsis is the major factor in the sterility of XYY mice, but double Y gene dosage couldn't be excluded from playing a role. Mice with four sex chromosomes were also produced (XYYY*X and XYY*XY*X) and it was determined that the presence of extra sex chromosomal material (whether or not it increased Y-specific gene dosage) interferes with spermatogenesis, possibly by causing problems with the inactivation of the sex chromosomes at pachytene. Two other examples of mice with partial spermatogenic impairment, XYSxra and XY*, were also studied and found to have a reduction in sperm counts proportional to the efficiency of sex chromosome pairing. Finally an inherited genetic effect was characterised that could partially overcome the requirement for synapsis of the meiotic "quality control". This effect allowed the usually sterile XYO mice to become fertile. Two factors, one major and another minor were found to be responsible for this inherited genetic effect.