Meiotic abnormalities in hybrid mice of the C57BL/6J × Mus spretus cross suggest a cytogenetic basis for Haldane’s rule of hybrid sterility

Abstract

Light- and electron-microscopic analyses of chromosomal pairing and recombination in F₁ and first-backcross generation mice of the C57BL/6J × Mus spretus cross revealed a variety of meiotic irregularities that could contribute to meiocyte loss and infertility. Pachytene anomalies included univalency, partially paired bivalents, homolog-length inequalities, nonhomologous pairing, and associations of asynapsed autosomal segments with the X chromosome. These phenomena were most prevalent in Fi males, which are invariably sterile. Although F[ females were qualitatively fertile, breeding data indicated significant reproductive impairment. Molecular analyses of X-linked and pseudoautosomal loci in sterile and fertile backcross males revealed that the failure of X-Y pairing and recombination is correlated with heterozygosity within the pseudoautosomal regions of the X and Y chromosomes. In addition to impairing fertility, the synaptic disturbances (such as localized asynapsis and nonhomologous pairing) observed in F₁ individuals can potentially alter recombinational patterns, thereby contributing to the genetic-map distortion observed with this interspecific cross. Together, the cytogenetic and reproductive data suggest that sex-related differences in the gametogenic process, quantitative differences in the incidence of synaptic irregularities in female and male meiosis, and phenomena associated with the X and Y chromosomes comprise the etiological basis of the sex-biased F₁ sterility. The differential gender-related effects of these cytogenetic phenomena may constitute the underlying basis of Haldane’s rule in mammals.

Reproductive Isolation in Hybrid Mice Due to Spermatogenesis Defects at Three Meiotic Stages

“…Moreover, cell-cycle arrest and apoptosis at metaphase of meiosis I have been observed in mutant mice having meiotic impairments such as lack of chiasmata and dissociation of homologous autosomes and XY chromosomes (Baker et al 1996;Lipkin et al 2002;Mark et al 2008). Previous studies revealed that genetic divergence between the parental species in the pseudoautosomal region of the XY chromosomes causes dissociation of these chromosomes in (B6 3 M. spretus) F 1 spermatocytes (Matsuda et al 1991(Matsuda et al , 1992Hale et al 1993). This dissociation is caused by asynapsis between sex chromosomes during pachytene (although X and Y chromosomes are still close to each other) and continues through metaphase I (Matsuda et al 1991(Matsuda et al , 1992Hale Figure 6.-Meiotic phenotypes of intersubspecific and interspecific F 1 hybrid males.…”

“…These animals include Drosophila (Joly et al 1997), stickleback fish Pungitius (Takahashi et al 2005), caviomorph rodent Thrichomys (Borodin et al 2006), house musk shrew Suncus (Borodin et al 1998), wallaby Petrogale (Close et al 1996), and genus Mus (Forejt and Iványi 1974;Matsuda et al 1992;Hale et al 1993;Yoshiki et al 1993;Kaku et al 1995;Gregorová and Forejt 2000;Elliott et al 2001Elliott et al , 2004Good et al 2008). Although reproductive isolation by spermatogenic impairment is a well-known phenomenon, its underlying genetic mechanism and molecular basis have remained elusive.…”

Male Hybrid Sterility in the Mule Duck is Associated with Meiotic Arrest in Primary Spermatocytes

“…Reproductive isolation mechanisms that restrict gene flow between different species can be categorized into two main types: one is the prezygotic (before the formation of zygotes/before fertilization) isolation mechanism, which prevents the eggs from being fertilized by the sperm of different species by gamete isolation due to gametic incompatibility and the environmental/ spatial and behavioral isolation of two populations; and the other is the postzygotic (after gamete fusion) isolation mechanism, which prevents the formation of fertile offspring after fertilization (Wu and Palopoli, 1994). When animals of genetically diverged populations hybridize, the resulting hybrids exhibit various abnormalities in development and/or reproduction, being lethal or sterile depending on the combination of parental species (Forejt and Iványi, 1974;Iwamatsu et al, 1984Iwamatsu et al, , 1986Iwamatsu et al, , 2003Matsuda et al, 1991;Hale et al, 1993;Sakaizumi et al, 1993;Yoshiki et al, 1993;Shimizu et al, 1997;Safronova et al, 1999;Elliot et al, 2001Elliot et al, , 2004Takahashi et al, 2005;Borodin et al, 2006;Sakai et al, 2007;Oka et al, 2010). Postzygotic barriers such as hybrid inviability, sterility, and/or breakdown (F 1 hybrids are viable and fertile while further hybrid generations such as F 2 and backcrosses are inviable or sterile) ensure reproductive isolation for fixing and maintaining species by preventing hybrids from passing their genes to the other population.…”

“…Postzygotic barriers such as hybrid inviability, sterility, and/or breakdown (F 1 hybrids are viable and fertile while further hybrid generations such as F 2 and backcrosses are inviable or sterile) ensure reproductive isolation for fixing and maintaining species by preventing hybrids from passing their genes to the other population. In vertebrates, the most common case of postzygotic reproductive isolation is spermatogenic disruption in F 1 hybrids between different species (Laurie 1997), which is often characterized by a small testis size, few or no spermatozoa, and a reduced number of germ cells, as is found in the medaka (Iwamatsu et al, 1984;Hamaguchi and Sakaizumi, 1992;Shimizu et al, 1997), wallaby (Close et al, 1996), mule and hinny (Chandley et al, 1974), and mouse (Matsuda et al, 1991;Hale et al, 1993). Incompatibility in the reproduction of these interspecific hybrids is believed to be mainly caused by a difference in the karyotypes and/or chromosome structures of parental species.…”

Mouse models for identifying genes modulating fertility parameters

“…In this case, generally, the female offspring is fertile whereas the male is sterile, showing a strong disruption of steroidogenic functions (Chubb and Nolan, 1987). The origin of this hybrid breakdown has been traced back to meiotic defects (Matsuda and Chapman, 1991;Matsuda et al, 1992;Hale et al, 1993). To date, nine loci inducing male hybrid sterility have been mapped on chromosomes X (Hstx1, Mhstq2 and Hst3) and 17 (Mhstq1, Hst1, Hst4, Hst5, Hst6 and Hst7).…”