Unitat Biologia Cel·lular, Facultat de Ciències, Universitat Autònoma de Barcelona, 08193 Bellaterra, Barcelona Spain)
Dear Sir,
We have read with much interest the paper by Yamamoto et al. in which the authors analyse the spermatids and eventually the sperm and seminiferous tubules of 24 men with non-mosaic Klinefelters syndrome using fluorescence in-situ hybridization (FISH), and come to the conclusion that few 47,XXY spermatogonia undergo meiosis with an XX pairing and a Y univalent and, as a result, also conclude that hyperploid round spermatids (24,XY and 24,XX) may be produced by meiosis of 47,XXY spermatogonia (Yamamoto et al., 2002).
Although the authors refer to the work of Mroz et al. (1998), they only take into consideration the Introduction to the paper, where the authors make an historical review of cases in which XXY primary spermatocytes seemed to have been detected in the pre-FISH era (Mroz et al., 1998
), and do so rather carelessly. As an example, the reference (Vidal et al., 1984
) includes only three authors because it was probably taken from the References of the paper by Mroz et al. (1998)
, published when Human Reproduction only requested the name of the first three authors followed by et al.
On the other hand, Yamamoto et al. (2002) do not mention the very important scientific contribution of the paper by Mroz et al. (1998)
where the authors clearly demonstrate that in the mouse XXY cells are meiotically incompetent, and suggest that any sperm produced must have originated from a normal XY cell line, no matter how residual.
Further, they have not discussed the work of Blanco et al. (2001) where using sequential centromere probes and chromosome painting on meiotic figures, the authors demonstrated that in humans XXY cells are also meiotically incompetent, as shown by the presence of only XY pachytenes both in mosaic and in so-called non-mosaic Klinefelters, and where by analysing sperm, they confirmed the hypothesis of Mroz et al. (1998)
in the sense that sperm disomic for the sex chromosomes had originated from an XY cell line by non-disjunction (Blanco et al., 2001
).
In addition, the authors own data provide information (Yamamoto et al., 2002). Of 24 non-mosaic Klinefelters studied, only those (12 of them) with XY spermatogonia (i.e., the mosaic patients) produced spermatids and, eventually, sperm, while in the other 12 patients with only XXY spermatogonia in their tubules, showed a complete absence of meiotic cells (although, based on morphometry alone, the authors sometimes use the denomination spermatogonia/primary spermatocytes). If XXY cells were able to enter meiosis, even if only few of them, then at least some spermatids should have been found in all patients. The absence of spermatids in patients without an XY cell line again suggest that only XY cells can enter meiosis.
Finally, if as Yamamoto et al. (2002) suggest, only spermatocytes with an XX bivalent and a Y univalent were capable of entering meiosis, the expected segregation would be X:XY, and no increase in hyperhaploid 24,XX spermatids should be expected. However, Yamamoto et al. (2002)
found a significant increase of 24,XX spermatids. Of course, it is possible to think that the Y-chromosome be lost during meiosis I, but then the authors should not have found any XY spermatids.
All in all, the results are more in line with those of Mroz et al. (1998) and Blanco et al. (2001)
than with the recurrent idea (by now mostly abandoned) that XXY cells may be meiotically competent.
Notes
1 To whom correspondence should be addressed. E-mail: josep.egozcue{at}uab.es
References
Blanco, J., Egozcue, J. and Vidal, F. (2001) Meiotic behaviour of the sex chromosomes in three patients with sex chromosome anomalies (47,XXY, mosaic, 46,XY/47,XXY and, 47,XYY) assessed by FISH. Hum. Reprod., 16, 887892
Mroz, K., Hassold, T. and Hunt, P. (1998) Meiotic aneuploidy in the XXY mouse: evidence that a compromised testicular environment increases the incidence of meiotic errors. Hum. Reprod., 14, 11511156
Vidal, F., Navarro, J., Templado, C., Brusadin, S. and Egozcue J. (1984). Synaptonemal complex studies in a mosaic, 46, XY/47, XXY male. Hum. Genet., 66, 306308[ISI][Medline]
Yamamoto, Y., Sofikitis, N., Mio, Y., Loutradis, D., Kaponis, A. and Miyagawa, I. (2002) Morphometric and cytogenetic characteristics of testicular germ cells and Sertoli cell secretory function in men with non-mosaic Klinefelters syndrome. Hum. Reprod., 17, 886896.