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Spermatogenic Defects in Sex Reversed Mice

Reporter and Curator: Dr. Sudipta Saha, Ph.D.

“Sex reversed” (Sxr) is an inherited form of sex reversal that causes XX and XO mice to develop as phenotypically normal males. Adult XYSxr^a mice exhibit varying degrees of spermatogenic deficiency but are usually fertile, while XOSxr^a mice have severe spermatogenic failure and are always sterile. The present quantitative spermatogenic analysis reports when these anomalies first appear during puberty. The results demonstrate that in XYSxr^a mice there was increased degeneration of pachytene spermatocytes and, to a lesser extent, meiotic metaphase stages. On average, there were only one-half the number of spermatids compared with the XY controls. The defect in XOSxr^a mice appeared a little later, with an almost complete arrest and degeneration during the meiotic metaphases.

A minority of XYSxr^a mice are sterile, and these may have testes as small as those from XOSxr^a mice. Adult XOSxr^a mice have consistently small testes and are invariably sterile. The reported results document the testicular defects in XYSxr^a and XOSxr^a testes as they first arise during puberty. The only other quantitative data on XYSxr^a and XOSxr^a spermatogenesis are for adult mice. A previous report described XYSxr^a testes as being a “mosaic” of normal and defective spermatogenesis. Recently a more extensive analysis was carried out of adult XYSxr^a and XOSxr^a testes. Once again there is good agreement with the present results in that the spermatogenic failure in XYSxr^a testes was predominantly between pachytene and diplotene, while in XOSxr^a testes the block was predominantly during the meiotic metaphases. To explain the spermatogenic anomalies in XYSxr^a and XOSxr^a testes, Burgoyne and Baker (1984) invoked the “meiotic pairing site” hypothesis of Miklos (1974). The other notable feature of the present study was the demonstration that the testicular deficiency is manifested earlier (with respect to age and spermatogenic stage) in XYSxr^a testes than in XOSxr^a testes. Krzanowska (1989) recently reported increased levels of X-Y univalence in pubertal XY males. So, it is suggested that this reduced efficiency of X-Y pairing at puberty that leads to the increased incidence of diploid spermatids in pubertal XYSxr^a males and to the presence of diploid spermatids in pubertal XY males. The other feature of pubertal XYSxr^a testes that deserves mention is the increase in the number of differentiating spermatogonia.

The conclusion is that most of the spermatogenic deficiencies in XYSxr^a and XOSxr^a testes can be explained in terms of the “meiotic pairing site” hypothesis, which links spermatogenic failure with sex chromosome univalence during meiosis. In XYSxr^a testes a variable proportion of pachytene spermatocytes have the X and Y unpaired, and the elimination of these cells explains the variable reduction in testis size and fertility. In XOSxr^a testes all spermatocytes have a univalent sex chromosome, accounting for the almost total spermatogenic block in these mice. It is suggested that the affected spermatocytes are eliminated earlier in XYSxr^a testes than in XOSxr^a testes, because two univalent sex chromosomes have more unpaired sites than the univalent X alone.

References:

Sutcliffe M. J., Darling S. M., Burgoyne P. S. (1991) Spermatogenesis in XY, XYSxra and XOSxra Mice: A quantitative analysis of spermatogenesis throughout puberty. Molecular Reprod. Dev. 30(2), 81–89.

Burgoyne P. S., Baker T. G. (1984) Meiotic pairing and gametogenic failure. In CW Evans and HG Dickinson (eds): “Controlling Events in Meiosis (38th Symp SOC Exp Biol).” Cambridge Company of Biologists, pp 349-362.

Miklos G. L. G. (1974) Sex-chromosome pairing and male fertility. Cytogen. Cell Genet. 13, 558-577.

Krzanowska H (1989) X-Y chromosome dissociation in mouse strains differing in efficiency of spermatogenesis: Elevated frequency of univalents in pubertal males. Gamete. Res. 23, 357-365.