Mahadevaiah et al. challenge a popular explanation for why would-be sperm cells die during meiosis, revealing that the main cause isn't too much broken DNA.
Meiotic cells fracture their DNA to allow crossing over. Repair of these double-stranded breaks (DSBs) occurs when homologous chromosomes pair up. Some researchers postulate a so-called pachytene checkpoint that triggers apoptosis of spermatocytes during meiosis if chromosomes fail to pair up (known as asynapsis) and too many unfixed DSBs remain. However, Mahadevaiah et al. hypothesized that spermatocyte mortality resulted from the failure to shut down the genes on the X and Y chromosomes, which can also be lethal for the cells. This silencing normally occurs during male meiosis.
To test the idea, the researchers first examined meiotic cells from male mice that lack a DSB instigator called Spo11. Asynapsis is prevalent in the cells but, despite the lack of DSBs, most of the cells perished. The team found that the majority of the spermatocytes didn't shutter the X and Y chromosomes. The researchers then checked three other types of mutant cells with widespread asynapsis, plenty of unrepaired DSBs, and high mortality. All three failed to silence the sex chromosomes.
However, evidence suggested a complication: the large number of DSBs in these cells hampered X and Y shutdown. To determine what happens in cells capable of sex chromosome silencing, Mahadevaiah et al. studied mouse spermatocytes that harbor a copy of the human 21st chromosome in addition to their normal chromosome complement. This loner has no chromosome to pair with and thus carries unrepaired DSBs. These cells managed to shut down their sex chromosomes and keep apoptosis levels low. Overall, the researchers say, the results point to a breakdown of sex chromosome silencing as the main cause of death for meiotic spermatocytes.