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It has been observed previously that there is an association between sex chromosome pairing failure during meiosis and spermatocyte death. An hypothesis is advanced suggesting a similar association between a disruption of sex chromosome pairing (specifically, a failure of Y chromosome pairing) and spermatocyte loss in XYY mice and men.

A quantitative histological analysis of ovaries from 3- and 5-day-old female mice heterozygous for the male-sterile reciprocal autosomal translocation, T(11;19)42H, revealed a marked reduction (by 65%) in the number of oocytes as compared to controls. These findings call into question the widely held view that chromosomal anomalies causing spermatogenic failure have no effect on oogenesis. It is suggested that during meiosis in males and females there is a mechanism operating which tends to eliminate cells which had incomplete chromosome pairing at the pachytene stage.

A cytogenetic and histological study of nine XO/XY or XO/XY/XYY mosaic mice revealed that XO germ cells were selectively eliminated from the spermatogenic epithelium. Although the XO contribution to the bone marrow in seven mice exceeded 50%, in only two cases were significant numbers of dividing XO spermatogonia present. These XO germ cells only occasionally progressed to meiosis and then degenerated prior to first meiotic metaphase. It was concluded that the mouse Y chromosome carries a "spermatogenesis gene" (or genes) which acts autonomously in the germ cells.

Sex-reversed XX male mice that carry the variant form of the testis-determining Sxr region, Sxr', do not express male-specific H-Y antigen. In a stock of mice segregating for Sxr', we detected an exceptional XX male that proved positive for H-Y antigen. DNA fingerprinting revealed that the banding pattern characteristic of Sxr' had been replaced by the pattern associated with the native testis-determining region of the normal Y chromosome of that stock, presumably by pairing and crossing-over between the two testis-determining regions of the father's Y Sxr' chromosome. Pairing between the two ends of such a chromosome in a loop-like configuration has been observed by electron microscopy. However, an anomalous crossing-over event of this kind would only give rise to the observed result if the native homologue of the Sxr region were situated on the very minute short arm of the Y chromosome. We therefore conclude that the two linked genes Tdy and Hya, controlling testis determination and H-Y antigen expression, respectively, are located on the short arm of the mouse Y chromosome.

The distribution of XX and XY cells in XX----XY chimaeric mouse testes was analysed by enzyme marker analysis of separated testicular tissues and by in situ DNA marker analysis of air-dried testicular cells and testis sections. XX cells contributed to the Leydig cells, the peritubular cells and the vascularized connective tissue of the tunica albuginea. The Sertoli cells, on the other hand, appeared to be exclusively XY. These results indicate that during the development of the testis, Sertoli cell differentiation is triggered by cell-autonomous activity of the Y chromosomal testis-determining gene Tdy. Subsequent steps in testis differentiation may be a consequence of Sertoli cell activity.

H-Y antigen negative XOSxrb mice, like their H-Y positive XOSxra counterparts, have testes; but, in contrast to XOSxra males, XOSxrb testes almost totally lack meiotic and postmeiotic stages of spermatogenesis. The quantitative analysis of the testes of XOSxrb males and their XY +/- Sxrb sibs, described in the present study, identified two distinct steps in this spermatogenic failure. First, there was a reduction in mitotic activity among T1 prospermatogonia, so that approximately half the normal number of T2 prospermatogonia were produced. Second, there was a dramatic decrease in the number of A3 and A4 spermatogonia and no Intermediate or B spermatogonia. These reductions were also largely due to decreased mitotic activity, there being a shortage of A1 and A2 spermatogonial divisions and no divisions among A3 or A4 spermatogonia. Mitotic activity among the T2 prospermatogonia and the undifferentiated A spermatogonia was normal. This means that the spermatogonial stem cells, which are a subset of the undifferentiated A spermatogonia, are unaffected in XOSxrb mice. Sxrb is now known to have arisen by deletion of DNA from Sxra. It is clear from the present findings that a gene (or genes) present in the deleted DNA plays a major role in the survival and proliferation of the differentiating A spermatogonia.

Oocytes with adhering follicle cells were sampled from ovaries obtained from 11 GPI-1A----GPI-1B chimaeras, comprising 10 females and 1 hermaphrodite. GPI analysis of individual oocytes revealed a marked bias towards the GPI-1B component in the germ line of this chimaeric combination. GPI-1B XY oocytes were identified in the ovary from the hermaphrodite, the bias towards the GPI-1B germ line perhaps helping to counterbalance the normally severe selection against XY oocytes. GPI analysis of follicle cells revealed a much more balanced contribution of the two components to this ovarian cell type. Importantly, GPI-1A follicle cells were identified in more than half the follicles from an XX----XY female in which the GPI-1A component was XY, supporting an earlier conclusion of Ford et al. (1974) that XY cells can contribute to the follicles of XX----XY female mice. It is suggested that XY cells can be recruited to form follicle cells in XX----XY chimaeras when there is a developmental mismatch between the two components, such that an ovary-determining signal produced by the XX component pre-empts the testis-determining action of the Y.

The growth and development of XO and XX mice were compared from 7 1/4 to 18 1/2 days of gestation. The 7 1/4-day XO egg cylinders were retarded in development (and consequently small) when compared with XX egg cylinders, and this lag in development remained until 10 1/2 days. By 12 1/4 days there was a considerable degree of 'catch-up', but this was not fully maintained. A subgroup of very severely retarded XO fetuses were preferentially located near the cervix. The placentas of XO fetuses were of normal size until 18 1/2 days when they were significantly larger than those of XX controls.

The mammalian Y chromosome carries a factor that initiates male sexual development by directing the fetal gonads to form testes. Wachtel and his colleagues proposed that this testis-determining function of the Y is mediated by the male-specific cell-surface antigen H-Y, originally defined by skin grafting. This attractive hypothesis, which has been widely accepted, was based on the assumption that serological tests using antisera raised against male cells were recognizing H-Y antigen. Although disputed this assumption is supported by some recent studies. However, mice have been described which develop testes but lack the cell-surface H-Y antigen as defined by T-cell-mediated transplantation tests. Thus, although it remains possible that a serologically detected male-specific antigen is responsible for testis determination, it seems that H-Y, as originally defined, is not. We show here that H-Y negative male mice, in losing the genetic information that encodes H-Y, have also lost genetic information required for spermatogenesis. This result identifies a gene on the mouse Y, distinct from the testis-determining gene, which is necessary for spermatogenesis, and raises the intriguing possibility that the product of this 'spermatogenesis gene' is H-Y antigen.

Microdensitometry of Feulgen-stained spermatogenic cell preparations from six XOSxr and four T31H/+ male mice revealed large numbers of spermatids with a diploid amount of DNA. In XOSxr mice, where the diploid spermatids usually constituted the majority of the spermatid population, there were large differences from mouse to mouse in the proportion of diploid spermatids (range, 35%-94%). There were large losses of both haploid and diploid spermatids during spermiogenesis, and the later condensed spermatids of both types were grossly misshapen. It is suggested that the omission of one meiotic division, and the other spermiogenic anomalies may be manifestations of a meiotic "quality control" mechanism that destroys the products of those pachytene spermatocytes which have unsynapsed or incompletely synapsed chromosomes.

In males spermatogenic impairment is associated with a wide range of chromosomal anomalies, including XYY trisomy, XO monosomy with sex reversal and heterozygosity for many structural rearrangements. Common to all these anomalies is the presence of unpaired chromosome segments during pachytene. The stage at which spermatogenic cells are lost varies markedly from one anomaly to the next. The present paper considers the possibility that there may be a common mechanism underlying these various manifestations of spermatogenic failure. An analysis of meiotic data from XYY mice had previously pointed to a causal relationship between the presence of unpaired elements at pachytene, and a failure to reach metaphase II (MII). In apparent contradiction to this is the observation that sex-reversed XO mice form reasonable numbers of round spermatids (implying progression beyond MII) despite the presence of the unpaired X. However, evidence is presented that the round spermatids of XO Sxr mice are diploid, the second meiotic division having been omitted. Most of these spermatids degenerate during spermiogenesis, but a few very abnormal sperm are produced. The female counterparts of male sterile chromosome anomalies are usually fertile, so the mechanism causing the spermatogenic failure has been presumed to be inoperative in females. However, recent work on female XO mice has revealed that although they are fertile as adults, there is nevertheless extensive oogenic failure (a 60% reduction as compared to controls) during late pachytene. It is proposed that there is a mechanism operating in both males and females which selectively removes gametogenic cells in which there has been meiotic pairing failure. In females the mechanism is not completely efficient, so that sufficient of the 'at risk' oocytes usually survive to allow fertility. In males the severity and stage of spermatogenic loss is presumed to be related to the extent of the pairing failure at pachytene. In male mammals spermatogenesis is disrupted by a wide range of karyotypic anomalies. These include XYY trisomy; XO monosomy with sex reversal; X- or Y-autosome translocations; partial or complete autosomal trisomies; heterozygosity for some autosome-autosome translocations; double heterozygosity for some Robertsonian translocations and heterozygosity for some other structural rearrangements (e.g. rings, insertions, some inversions). Common to all these anomalies is the presence of incompletely paired (synapsed) regions at pachytene. The severity of the spermatogenic impairment and the stage most affected vary widely.(ABSTRACT TRUNCATED AT 400 WORDS)