3-Monochloro-1,2-propanediol disrupts ovarian germline stem cell maintenance via Golgi stress-induced autophagy in Drosophila.

The ubiquitous food processing contaminant 3-monochloro-1,2-propanediol (3-MCPD) poses a potential threat to female reproductive health, yet the underlying mechanisms remain largely undefined. Here, we demonstrate that 3-MCPD exposure impairs ovarian function by disrupting germline stem cell (GSC) maintenance in Drosophila. 3-MCPD exposure dose-dependently induced ovarian atrophy, reduced fecundity, and GSC loss. Mechanistically, 3-MCPD triggered Golgi stress, leading to Mitf-dependent transcriptional upregulation of Atg9. This, in turn, activated autophagy, which selectively degraded E-cadherin, a critical adhesion molecule for GSC maintenance. Notably, GSC-specific E-cadherin overexpression or Atg9 knockdown effectively rescued 3-MCPD-induced ovarian defects. We further identified a direct physical interaction between Atg9 and E-cadherin, corroborated by immunofluorescence co-localization and AlphaFold3 modeling, which revealed high-affinity binding interfaces that likely mediate this selective autophagic degradation. Both E-cadherin and Atg9 exhibit high evolutionary conservation, underscoring the translational relevance of our findings. This study delineates a novel Golgi stress-Mitf-Atg9 axis through which a prevalent food contaminant compromises female fertility, thereby identifying potential targets for intervention.