Gonadal atrophy is the most typical and dramatic manifestation of intraspecific hybrid dysgenesis syndrome leading to sterility in Drosophila melanogaster dysgenic progeny. The P-M system of hybrid dysgenesis is primarily associated with germ cell degeneration during the early stages of Drosophila embryonic development at elevated temperatures. In the present study, we have defined the phase of germ cell death as beginning at the end of embryogenesis immediately following gonad formation. However, the temperature-dependent screening of germ cell developmental patterns in the dysgenic background showed that early germ cells are susceptible to the hybrid dysgenesis at any Drosophila life-cycle stage, including in the imago. Electron microscopy of germ cells after dysgenesis induction revealed significant changes in subcellular structure, especially mitochondria, prior to cellular breakdown. The mitochondrial pathology can promote the activation of cell death pathways in dysgenic germ cells, which leads to gonadal atrophy.