Autophagy Protects Murine Preputial Glands Against Premature Aging and Controls Their Sebum Phospholipid and Pheromone Profile

The study investigated the role of autophagy in murine preputial glands, which are large lipid and hormone secreting sebaceous organs in mice. The researchers found that suppression of ATG7-dependent macroautophagy/autophagy in these glands significantly delayed the onset of age-related ductal ectasia, influenced lipid droplet morphology, and contributed to the complete dissolution of mature sebocytes during holocrine secretion. Single cell RNA sequencing revealed downregulation of many genes involved in lipid metabolism and oxidative stress response in ATG7-deficient glands. The lipid composition of these glands showed decreased levels of all phospholipid classes, except choline plasmalogen, and an accumulation of diacyl glycerides. Mass spectrometric imaging demonstrated a decrease in phosphatidylcholine (PC 34:1) in immature and mature sebocytes. The study also found a strong reduction in the amounts of the pheromone, palmityl acetate. The findings suggest that autophagy in the preputial gland is crucial for gland homeostasis, cell breakdown during holocrine secretion, and regulation of phospholipid and fatty acid metabolism, as well as pheromone production.