Worm Breeder's Gazette 12(3): 109 (June 15, 1992)

These abstracts should not be cited in bibliographies. Material contained herein should be treated as personal communication and should be cited as such only with the consent of the author.

Feminizing Triploid Males

Philip Meneely, Fred Hutchinson

Cancer Research Center, Seattle WA 98104

The analysis of feminizing elements, both by us and by Madl and Herman (1979), has used triploid animals with two X chromosomes (3A;2X). These animals are males but their sexual phenotype is sensitive to both X-chromosome duplications and microinjected X-chromosome DNA. In each case, the additional X-chromosome material causes some 3A;2X animals to develop as intersexes. Our thinking about the chromosomal signal for normal sex determination has been based on these animals with an unusual chromosome constitution, so it seemed worthwhile to re-examine these experiments.

The basic question is this: do the treatments that feminize 3A;2X males also affect diploid (2A;1X) males? The answer is that they do not. I can inject feminizing elements at a concentration that is 107 in excess of what is needed to feminize 3A;2X males with no effect on diploid males. Likewise, putting two duplications, each of which feminizes 3A;2X males, into a diploid male also has no effect on its sexual phenotype. For example, males with both mnDp57 and mnDp1 O(estimated to be more than half of a second X chromosome) are small and scrawny as if dosage compensation is affected but are sexually normal. A simple interpretation of these results is that some X-linked element (a gene, a region, a sequence) must be present in two copies for female development; this postulated element is not present on the duplications used or the injected feminizing element. [Of course, there could also be more than one element which must be simultaneously duplicated and the particular duplications being used don't carry both elements.]

But the story gets more complicated. Both in the original Madl and Herman experiments with X-chromosome duplications and our experiments with injected DNA, diploid males were mated with tetraploid hermaphrodites. The 3A;2X progeny that arise get both X chromosomes from the mother and none from the father. In diploids, the origin of the X chromosome makes no difference in sex determination or viability. But in these 3A;2X animals, the origin of the X chromosome may make a difference. When tetraploid males (4A;2X) are mated to diploid hermaphrodites, the resulting 3A;2X animals are males with one chromosome from each parent. However, introducing X-chromosome duplications or injecting a feminizing element (via the diploid mother) in these crosses results in very few intersexes, about 20-fold less than the same duplication or feminizing element with a tetraploid mother. This suggests that the inheritance of a diploid (2A;2X) oocyte is important in the feminization of 3A;2X males.

From this, there appear to be at least three important components involved in feminizing triploid males. First, since 3A;2X animals are males, there has to be some additional "X-chromosome material", either a duplication or injected X chromosome DNA; this "X-chromosome material" can apparently be introduced either zygotically (like the duplication) or maternally (like the injected DNA). It is not clear what this "X-chromosome material" does, but one hypothesis is that it competes with the normal X chromosome for some protein present in limited amounts in the oocyte or the mother's gonad. Second, feminization occurs much more frequently in animals arising from 2A;2X oocytes. Again, this may be because of the competition for a limited resource in the mother's gonad or the oocyte. Third, since 4A;2X males are not feminized (at least by injected feminizing elements) even when they arise from 2A;2X oocytes, there must also be a zygotic autosomal component that can ensure male development.