Abstract
Lack of crossing-over in meiosis can trigger an apoptotic response at metaphase I by the spindle assembly checkpoint (SAC). In contrast to females, segregation of sex chromosomes in males poses a particular challenge as recombination and chiasma formation is restricted to the pseudoautosomal region, the small region of homology between X and Y chromosomes. Existing data indicate that low levels of crossover failure in male meiosis can be tolerated without compromising fertility, while high levels of X-Y dissociation (in ≥70 % of cells) result in widespread apoptosis and subsequent infertility, demonstrated earlier, e.g., in Spo11β-only mice. Here, we explore the threshold of X-Y recombination failure frequency that is compatible with fertility. We show that in Spo11β-onlymb mice with a mixed genetic background, in contrast to Spo11β-only mice with a C57BL/6 background, X-Y pairing fails in ~50 % of cells but this still allows for sperm production without any overt impact on fertility. We also review data on apoptosis and fertility from other achiasmate mouse models and propose that the incidence of homolog dissociation that can be tolerated in vivo without compromising male fertility lies between 50 and 70 %.
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Acknowledgments
We are grateful to Scott Keeney, Maria Jasin, and Robert Benezra (Memorial Sloan-Kettering Cancer Center, New York) for providing mice and to Elina Hakonen from Timo Otonkoski’s Laboratory (University of Helsinki), Noora Kotaja (University of Turku), and Rocio Sotillo (EMBL, Italy) for their advice on experimental procedures. Assistance was provided by the following core facilities at the University of Helsinki: the Tissue Preparation and Histochemistry Unit, the Laboratory Animal Center, and the Biomedicum Imaging Unit.
Funding
L.K. is an Academy Research Fellow of the Academy of Finland and the recipient of a Marie Curie Career Integration Grant (European Commission Framework Programme 7). This work was supported by the Academy of Finland (funding decision number 263870), Biocentrum Helsinki, and the Sigrid Juselius Foundation.
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Imrul Faisal declares that he has no conflict of interest. Liisa Kauppi declares that she has no conflict of interest.
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All applicable national and institutional guidelines for the care and use of animals were followed.
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This article is part of a special issue on “Recent advances in meiotic chromosome structure, recombination, and segregation” edited by Marco Barchi, Paula Cohen, and Scott Keeney
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Faisal, I., Kauppi, L. Sex chromosome recombination failure, apoptosis, and fertility in male mice. Chromosoma 125, 227–235 (2016). https://doi.org/10.1007/s00412-015-0542-9
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DOI: https://doi.org/10.1007/s00412-015-0542-9