OnXinactivation inXOembryos of mammals

Abstract

By analogy with the situation in coccids it is suggested that in mammalian XO embryos the single X turns heterochromatic in some cells, but that such a change does not result in cell death because the X then reverts back to an euchromatic and active state. This testable alternative to the Gartler-Sparkes hypothesis would imply that the anomalies of the XO Turner syndrome are largely due to imbalance of sex-linked genes rather than developmental damage resulting from cell death and that mammalian X inactivation might become reversed in response to special developmental needs.In the vast majority of mammalian females with altered X chromosomes, it is the abnormal X that is late-replicating and forms sex chromatin. This non-randomness in inactivation has been interpreted by Gartler & Sparkes (1963) as being due to cell selection, the cells in which the normal X was inactive being lethal or less able to survive. Similarly, in XO embryos, according to their reasoning, in some cells the single X turns heterochromatic and these cells would not be expected to survive because they would in effect be nullisomic for the X chromosome. The resulting cell death could account for the abnormal features of XO women, including their short stature. This is an appealing idea and has been frequently discussed (e.g. Lyon et al. 1964; Beutler, 1964;Polani & Polani, 1969), most recently by Hecht & Macfarlane (1969). Implicit in the Gartler-Sparkes hypothesis is the idea of the irreversibility of X inactivation. Indeed Lyon (1961) made such irreversibility an important feature of the first statement of her hypothesis. However, since cytological data about these early events in XO (and other chromosomally abnormal) embryos are lacking, it is not known whether this interpretation is the correct one.On the basis of experience with an analogous situation in coccids (a group of homopteran insects), we wish to suggest the possibility that in XO embryos the single X turns heterochromatic, as expected, in some cells, but that such cells do not die because the X then reverts back to an euchromatic and active state. A precedent for such a sequence exists among mealy bug embryos from triploid female x diploid male matings. During a cytological study of over 300 embryos resulting from such crosses, Chandra (1963) observed that in twelve of them there were haploid sectors of varying sizes, apparently originating from supernumerary sperm. Five of these embryos were male and showed heterochromatization of the paternal complement in the diploid, zygotic sector of the embryo. In two of these embryos, which were very young, the haploid complement first turned heterochromatic (as paternal chromosomes normally do in male embryos) and then in a series of gradations reverted back to an euchromatic state. It thus appears that in coccids a heterochromatic set cannot remain as such without at least one or more euchromatic chromosomes in the same nucleus (Chandra, 1963). This change in condensation was referred to as deheterochromatization, but, more recently,...

The Mortality of Human Xo Embryos

“…It is still possible, however, that random inactivation of the single X may cause abortion of XO conceptuses early during the first trimester of gestation, as suggested by Gartler & Sparkes (1963). Even if such an inactivation occurred, however, it might not inevitably lead to the death of the cell because the X chromosome might revert to a euchromatic active state like that observed in coccids (Chandra, 1963(Chandra, , 1970Brown, 1966) and in mice (Cattanach, Pollard & Perez, 1969). So far, no reactivation of the human X chromosome has been observed in vivo or in cell cultures following treatment with different substances (Comings, 1966).…”