Probiotics and Prebiotics

Autophagy is a cellular process that delivers cytoplasmic material to the lysosome for recycling. It is stimulated above the basal or resting rate when nutrients are scarce, cells are under stress, or damaged organelles need to be degraded. High throughput transcriptional profiling suggested that autophagic involvement in early disease resistance and stress management differed between male and female fish. Since, sex steroid and their responsive receptors, especially estrogen and estrogen receptors (ERs), abundances are sexually dimorphic, we deduced that sex-biased autophagy may be regulated by ERs. To prove that, we used ER and ER2 knockout (KO) medaka and analyzed the alterations in the autophagic genes and protein expression in the liver and gonad. We found significantly increased mTOR expression in ER-KO, but not in ER2-KO female fish. This suggested differential involvement of ERs in autophagic regulation, which was further confirmed by ULK and Beclin transcription, and mitochondrial population. Interestingly, the LC3 (the last major autophagy factor) contents/cell and LC3 positive cells were increased significantly in ER-KO fish. In-depth analysis showed that LC3 nuclear-cytoplasmic transports were partially (ER2-KO) or completely (ER-KO) compromised due to SIRT/DOR protein regulation in the nucleus. We also found that autophagy is not only instrumental in germ cell degeneration but also important for oocyte and sperm formation/development in the ER-KO fish. Cumulatively our data highlights the sexbiased autophagy and ER association, stress-influenced apoptosis/autophagy cell fate decision, and the immense significance of autophagy in fish liver and gonad physiology.