Sex Chromosome Aneuploidy In The Germline

The effects of both Klinefelter and Turner syndrome's on gonad development and fertility reflect the fact that inactivated X chromosomes of XXY males are reactivated in the germ cells of the testes create, which creates an excess of X-linked genes in the testes. Similarly, in normal XX females the inactivated X is reactivated in the germ cells and oogenesis requires two active Xs. Thus, X0 females will lack the necessary second X in their oocytes. Although one X does inactivate in the germ cell progenitors of early female embryos, it is eventually reactivated in oocytes before meiosis. This reactivation reflects a stringent requirement for two X chromosomes in oogenesis. The absence of the second X chromosome in Turner syndrome females causes rapid death (atresia) of oocytes during fetal development. The result is both sterility and small rudimentary ovaries. Similarly, Klinefelter men also reactivate the second (inactivated) X chromosome in the developing testis. The presence of the extra X in a male germ cell causes death of the male germ cells during early puberty and subsequent atresia of the testes. This testicular atrophy results in a great diminishment in the ability of many of these males to make testosterone. The resulting testosterone deficiency may explain many, if not most, of the characteristics of Klinefelter syndrome.


If the somatic cells only require one X, and all that the Y does is determine sex, why is Turner syndrome so often lethal to early embryos, and why are live-born females affected with any unusual phenotypic characteristics? As noted above, 99.9% of all X0 conceptions are miscarried spontaneously in utero. Thus possessing only one X chromosome, minus a Y as well, is almost always lethal to the zygote, yet males can survive with only one X chromosome; we also know that females inactivate one of their X chromosomes in all of their somatic cells. So why is that second X chromosome so important? One would think that if a normal female has only one X chromosome active anyway, what is the big deal with having only one X? Part of the answer may lie in the problems of gene dosage we talked about in Chapter 20: a small number of essential genes on the X escape inactivation in cells with two or more X chromosomes. The existence of such genes provides a straightforward explanation for Turner Syndrome. X0 females possess only one copy of such genes, whereas both XX females and XY males possess two copies.

The sterility of Turner females, like that of XY males missing the TDF gene, reflects the requirement for two functional X chromosomes in the female germline, but what about the other phenotypes? Where do they come from, and why are they so variable? Given the very high lethality of Turner syndrome, why do such individuals ever make it to birth, much less beyond? Perhaps the answer lies in other genetic variations in the genomes of these individuals that compensate for something missing from the X, or perhaps even differences in the copies of the X chromosome that turn up in X0 individuals that survive.

There also may be another explanation: perhaps the reason for the survival of the rare Turner female and the vast phenotypic variability among such live-born females may be attributed to what scientists call mosaicism. Some liveborn cases of Turner syndrome may be due to the fact that these surviving girls are not composed solely of X0 cells: they are composed of both X0 and XX cells. The loss of a single X chromosome, during mitosis and not meiosis, in one cell out of several cells present very early in zygotic development may produce a combination of both XX and X0 cells. Thus the resulting individual possesses both XX and X0 cells. As long as an XX karyotype is present in those cells that absolutely require two X chromosomes, the individual will survive. Those cells that do not require two X's will be able to survive as either XX or X0 cells. The more X0 cells the individual possesses, the more severely affected the individual will be, whereas the more XX cells the individual possesses, the more normal the individual will be. If different Turner females each have a different fraction of X0 cells in their bodies, it makes sense that the phenotype would be so variable.

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  • Flavio
    Why x is reactivated in germline?
    8 months ago

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