Testis-Specific PDHA2 Is Required for Proper Meiotic Recombination and Chromosome Organisation During Spermatogenesis.

Abstract

Proper segregation of homologous chromosomes during meiosis requires crossovers that are tightly regulated by the chromosome structure. PDHA2 is the testis-specific paralog of PDHA1, a core subunit of pyruvate dehydrogenase. However, its role during spermatogenesis is unclear. We show that PDHA2 knockout results in male infertility in mice, but meiotic DSBs in spermatocytes occur normally and are efficiently repaired. Detailed analysis reveals that mid/late recombination intermediates are moderately reduced, resulting in fewer crossovers and many chromosomes without a crossover. Furthermore, defective chromosome structure is observed, including aberrant histone modifications, defective chromosome ends, precocious release of REC8 from chromosomes and fragmented chromosome axes after pachytene. These defects contribute to the failure of pyruvate conversion to acetyl-CoA, resulting in decreased acetyl-CoA and precursors for metabolites and energy in the absence of PDHA2. These findings reveal the important functions of PDHA2 in ensuring proper crossover formation and in modulating chromosome structure during spermatogenesis.