An analysis of meiotic impairment and of sex chromosome associations throughout meiosis in XYY mice

Abstract

The existing XYY meiotic data for mice present a very heterogeneous picture with respect to the relative frequencies of different sex chromosome associations, both at pachytene and diakinesis/metaphase I. Furthermore, where both pachytene and diakinesis/MI data are available for the same males, the frequencies of the different configurations at the two stages are very different. In the present paper we utilise “XYY” and “XY/XYY” mosaic mice with cytologically distinguishable Y chromosomes to investigate the factors responsible for this heterogeneity between different males and between the two meiotic stages. It is concluded (1) that the initial pattern of synapsis is driven by the relatedness of the three pseudoautosomal regions (PARs); (2) that the order and extent of PAR synapsis within radial trivalents are also affected by PAR relatedness and that this leads to chiasmata being preferentially formed between closely related PARs; (3) that trivalents with a single chiasma resolve into a bivalent + univalent by the diakinesis stage; (4) that although many spermatocytes with asynapsed sex chromosomes are eliminated between pachytene and diakinesis, those that survive this phase of elimination progress to the first meiotic metaphase (MI) and accumulate in large numbers, leading to an over-representation of those with univalents as compared to radial trivalents; and (5) that the arrested MI cells are eventually eliminated, so that very few “XYY” cells contribute products to MII.

Evidence that sex chromosome asynapsis, rather than excess Y gene dosage, is responsible for the meiotic impairment of XYY mice

“…The accompanying paper by Mahadevaiah et al (2000) provides evidence that this drop in radial trivalent frequency is due to two main factors. First, only those trivalents in which all three axes are tied together by the presence of two chiasmata retain this association through to MI, while those with a single chiasma separate into a univalent plus a bivalent.…”

“…XYY mice suffer severe spermatogenic impairment (Cattanach and Pollard, 1969;Rathenberg and Müller, 1973;Evans et al, 1978;Das and Kar, 1981;Tease, 1990;Mahadevaiah et al, 2000), although some sperm are produced. Consequently, they are almost always sterile unless there is germinal mosaicism for an XY cell line (our unpublished data).…”

“…The spermatogenic impairment is a consequence of spermatocyte death during pachytene and at MI, the balance between the two phases of loss being affected by the genetic background of the mice (Palmer et al, 1990;Mahadevaiah et al, 2000). Synaptonemal complex analysis has established that a large proportion of pachytene spermatocytes have a sex chromosome configuration consisting of a bivalent plus a univalent, but in some cells the three sex chromosomes associate to form a trivalent, which could represent full PAR synapsis (Palmer et al, 1990;Tease, 1990;Mahadevaiah et al, 2000). Burgoyne and Biddle (1980) have suggested that the trivalent formation allows some cells to complete spermatogenesis.…”

A Model System for Study of Sex Chromosome Effects on Sexually Dimorphic Neural and Behavioral Traits

“…To test the hypothesis that this inconsistency was the result of variability induced by uncontrolled exposure of fetal females to androgens originating from adjacent males in utero (vom Saal and Bronson, 1978), litters of mice were produced containing only females. X Y Ϫ Yqdel RIII males (Mahadevaiah et al, 2000) were mated to M F1 females. The Yq-del chromosome is of RIII strain origin and carries a deletion of Yq (Conway et al, 1994).…”

Function of the Sex Chromosomes in Mammalian Fertility

“…For Double Y syndrome men, the reproductive outlook varies; the extra Y chromosome is often lost during the early spermatogonial stages and this generates XY (euploid) cell lines that can complete spermatogenesis and support fertility (Chandley 1997;Shi and Martin 2000). In XYY men and mice in which XY cell lines do not arise, infertility results, with germ cell losses occurring during pachytene and the meiotic divisions (Speed et al 1991;Solari and Rey Valzacchi 1997;Mahadevaiah et al 2000;Rodriguez et al 2000).…”