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As a consequence of whole genome duplication, resulting polyploids are thought to have enhanced adaptability and novel traits such as resistance to climate-relevant stresses like drought. However, newly formed (neo)polyploids, due to the presence of additional chromosome sets, often show compromised meiotic stability and low fertility which can be reverted in established polyploids through several evolved meiotic adjustments. Deciphering how nature solves the problem of meiotic instability has the potential to inspire engineered solutions to unleash the use neo-polyploids to generate new crops. For this goal, we sought to study Arabidopsis arenosa established tetraploids and phenocopy its stable meiosis, using meiotic mutants, in A. thaliana neo-tetraploids. First, we performed a computational analysis of a large set of Structured Illumination Microscopy (SIM) images by measuring the abundance and distribution of two meiotic proteins (ASY1 and HEI10) and we observed that the co-dynamics of these two proteins is modified in the evolved meiosis of established tetraploids. Encouraged by these results highlighting the importance of HEI10, we combined mutations for its gene and one additional (TAF4B) in A. thaliana to generate a more stable neo-tetraploid meiosis. This stabilization came from a reduction in meiotic crossovers, which prevented multiple copies of chromosomes to engage during meiosis and favoring pair-wise interactions as it happens in diploids and established tetraploids. These results illustrate the validity of manipulation of meiotic genes as a strategy to generate more stable neo-polyploids.