Rearing scheme for combined female lethality and multifactorial reproductive sterility systems. A Under regular rearing conditions, tetracycline (TET) is added to the food to repress the female lethality, quinic acid (QA) is not required for rearing. B The adult parents of the release generation will be changed to food without TET, still also without QA. This is necessary to avoid suppression of the early embryonic lethality in the next generation by maternally transferred TET to the oocyte. The female lethality system is still off, since the early embryonic promoter is not driving tTA at adult stages. C The release generation is then reared on food without TET but with added QA. Due to the lack of TET the female lethality system is switched on and the females die during early development. The QA leads to the activation of the Q system that leads to the expression of a site specific recombinase, which in turn mediates the spermatogenesis-specific expression of the Cas9 endonuclease by removing a recombination site-flanked spacer cassette. D The released males (no TET, no further QA) express high levels of the endonuclease Cas9 and multiple guide RNAs during spermatogenesis causing shredded chromosomes that will lead to lethal aneuploidy in the next generation.