Defects in Meiotic Recombination Delay Progression Through Pachytene in Mouse Spermatocytes

Abstract

During meiosis, recombination, synapsis, chromosome segregation and gene expression are coordinately regulated to ensure successful execution of this specialised cell division. In many model organisms, checkpoint controls can delay meiotic progression to allow defects or errors in these processes to be repaired or corrected. Mouse spermatocytes possess quality control checkpoints that eliminate cells with persistent irreparable defects in chromosome synapsis or recombination, and here we show that a spermatocyte checkpoint regulates progression through pachytene to accommodate delays in meiotic recombination. We have previously show that the appearance of early recombination foci is delayed in Tex19.1-/- spermatocytes during leptotene/zygotene, but some Tex19.1-/- spermatocytes still successfully synapse their chromosomes. Therefore, we have used autosomally synapsed Tex19.1-/- mouse spermatocytes to assess the consequences of delayed recombination on progression through pachytene. We show that these pachytene spermatocytes are enriched for early recombination foci. This skew is not accompanied by cell death and likely reflects delays in the generation and/or maturation of recombination foci. Moreover, patterns of axis elongation, chromatin modifications, and histone H1t expression are also all skewed towards earlier substages of pachytene suggesting these events are co-ordinately regulated. Importantly, the delay in histone H1t expression in response to loss of Tex19.1 does not occur in a Spo11 mutant background, suggesting that histone H1t expression is being delayed by a recombination-dependent checkpoint. These data indicate that a recombination-dependent checkpoint operates in mouse spermatocytes that can alter progression through pachytene to accommodate spermatocytes with some types of recombination defect.