Endocrine Abstracts

Klinefelter syndrome (47XXY male) (KS) is the most common sex chromosome disorder in men. The phenotype is diverse including: infertility, hypogonadism, impaired cognition, behavior disorders, increased autoimmunity and osteopenia. We have studied osteopenia, learning dysfunction, germ cell loss, and testosterone deficiency in 41 XXY mice bred by two separate methods. We have characterized the germ cell loss by apoptosis and germ cell migration as the mice progress from day 1 to 10 days of age and subsequently into adulthood. These studies confirm the phenotypic similarities of XXY mice to human KS. Mice have low testicular venous and peripheral blood levels of testosterone (with elevated LH and FSH levels) yet have normal to elevated intratesticular testosterone levels. This suggests a testosterone sequestration effect within the testes. The ability of the testes to synthesize testosterone is present and augmented by response to LH in Leydig cells and in whole testis in culture. Germ cell transplants from XY mice to XXY mice shows seeding of the GFP labeled XY donor germ cells into 41XXY immature and adult recipients with progression to spermatocyte or spermatid germ cells. While overexpression of non-X inactivated genes is believed to be a likely molecular basis for the disorder, the reasons for phenotypic heterogeneity are only partially understood.

Declaration of interest: The authors declare that there is no conflict of interest that could be perceived as prejudicing the impartiality of the research project.

Funding: This work was supported, however funding details are unavailable.