Meiotic aneuploidy in the XXY mouse: evidence that a compromised testicular environment increases the incidence of meiotic errors.

Male mammals with two X chromosomes are sterile due to the loss of virtually all germ cells in the differentiating testis. The survival of rare germ cells, however, can give rise to patches of normal-appearing spermatogenesis in the adult testis. Intracytoplasmic sperm injection (ICSI) makes possible the establishment of a pregnancy using spermatozoa from severely oligozoospermic men and, indeed, has been successful using spermatozoa from human 47,XXY (Klinefelter syndrome) males. The risk of an abnormal pregnancy, however, may be significantly increased since several studies have demonstrated elevated levels of aneuploidy in spermatozoa from Klinefelter syndrome men. This has been suggested to reflect the consequences of meiotic segregation in XXY germ cells; however, it is also possible that it is a consequence of abnormalities in meiotic regulation in the XXY testis. We have addressed this question experimentally in the XXY male mouse. Analysis of testicular spermatozoa from XXY and control males demonstrates a significant increase in meiotic aneuploidy in the XXY mouse. Since previous studies have demonstrated that germ cells in the adult XXY testis are exclusively XY, the meiotic abnormalities observed must be attributable to segregation errors in XY germ cells. These findings have potential significance for ICSI pregnancies using spermatozoa from other types of male factor infertility patients, since they raise the possibility that increased meiotic errors are a generalized feature of the severely oligozoospermic testis.