Mus musculus strain:C57B6 Raw sequence reads
PDHA2 is the testis-specific ortholog of PDHA1, a core subunit of pyruvate dehydrogenase. However, its roles are unclear during spermatogenesis. Here, we showed that PDHA2 knockout resulted in male mouse infertility. Detailed analysis revealed that meiotic DSBs occurred normally and were repaired timely in spermatocytes. However, mid/late recombination intermediates were moderately decreased from early pachytene. As a result, the number of crossovers was decreased and many chromosomes failed to get a crossover. Moreover, defective chromosome structure was observed, including decreased histone acetylation and increased methylation and ubiquitination, defective chromosome ends, precocious removal of REC8 from chromosomes during pachytene, and fragmented chromosome axes after pachytene in this mutant. These defects contribute to the failure in the conversion of pyruvate into acetyl-CoA which results in decreased acetyl-CoA and precursors for metabolites and energy as observed in the absence of PDHA2. These findings reveal the important functions of PDHA2 not only in ensuring proper crossover formation but also in modulating chromosome structure during spermatogenesis.