I zyxwvutsrqponm ANDROLOGIA zyxwvutsrqpon 24, 1-1-16 (1992) ACCEPTED: NOVEMBER 10, 1991 zy Chromosome variability and germ cell development z in the house mouse* C. A. Redi and S. Garagna Key words. Germ cell development - chromosome - aneuploidy - mouse Summary. Structural heterozygosities of the karyotype have detrimental effects on the meiotic process, resulting very often in impairment of fertility in the carriers. Both male and female germ cell development are affected by chromoso- mal variability although spermatogenesis seems particularly prone to be affected, probably because of the intrinsic characteristics of the male germ cell cytodifferentiation process (i.e. the his- tological architecture of the seminiferous epi- thelium). However, euploid and aneuploid sperm do not seem to differ in the molecular organiz- ation of the genome they carry, thus explaining the almost regular capacity to accomplish the first zygotic developmental stages by the aneu- ploid sperm (aneuploid both for gametogenic genes and for entire chromosomal arms). A survey of the molecular and morphological data avail- able on germ cell development in conditions of chromosomal rearrangement leads to the con- clusion that the current hypotheses accounting for this phenomenon can only partly explain it. A working hypothesis is proposed which considers the three-dimensional changes (produced by structural heterozygosity) in the spatial order of chromosomes within the nucleus as the primary cause potentially able to trigger distorted func- tioning of the germ cells. Introduction A normally arranged karyotype structure is an essential prerequisite for regular germ cell devel- Dipartimento di Biologia Animale e Centro di Studio per 1’Istochimica del C.N.R., Universita’ di Pavia, Piazza Botta 10, 27100 Pavia, Italia. Correspondence: Prof. Dr C. A. Redi, Dipartimento di Biologia Animale Piazza Botta, 10-27 100 Pavia, Italy. * Dedicated to Professor Dr Werner Hilscher on the occasion of his 65th birthday. opment, as has been clearly shown by the study of several animal models of chromosome varia- bility (Gropp & Winking, 1981; Redi zy et al., 1982; Searle, 1982; Redi zyxw et al., 1984; de Boer et al., 1986; Handel, 1987; Redi & Capanna, 1988; Jaafar et al., 1989; Richler et al., 1989; Garagna et al., 1989; Redi et al., 1990). The vast majority of karyotype structure changes (due either to hybridization phenomena or to mutations) have great potentialities for affecting fertility. Although this causal relationship is unquestionable, it is still true that we understand little about the causes of the detrimental effects of karyotype structural variability on the genetic control of gametogenesis (Redi et al., 1990, 1991). In other words, the life history of a germ cell from the genetic point of view is far from clear. We have a tangled mass of data on germ cell production and differentiation showing that, with hetero- zygous karyotypes, the impairment of this process can vary from nil to sterility. Supporters of Lifsch- ytz & Lindsley (1972, disturbances of the dor- mant pachytene stage of the X-chromosome) and of Miklos (1974, failure to saturate meiotic pair- ing sites) found inconsistencies in chromosomal cases that cannot be explained by their favoured hypothesis (Handel, 1987). Thus, we have an uncertain view of the phenomenon since it can only partly be accounted for by the epigenetic effects exerted on the genetically determined fate of a germ cell by the cytoarchitectural properties of the mammalian gonad which, mainly in males, can either rescue or impair the germ cell develop- ment programme. It would probably be better to consider the explanations of Lifschytz & Lindsley, and of Miklos (of chromosomally derived impairment of fertility) as possibly accounting for some late phenomena of chromo- some behaviour in the presence of structural heterozygosities rather than for the primary trig- gering of distorted developmental processes. As suggested by Handel (1987), if we want to sustain