(W1134) Health Conferred By Epithelial Cells and Their Role In Paraphagy Promoted Cholesterol Clearance and Lipid Metabolism During Epididymal Sperm Maturation
Principal Investigator University of Saint Joseph - Macau, Macao, Macau
Abstract: Mammalian sperm undergo functional maturation in the epididymis, preparing themselves for the long and challenging journey to begin a new life by successfully fertilizing an oocyte. Defects in epididymal sperm maturation are closely related to male infertility and paternal health and even the health of offspring. In the epididymis, the halted translational machinery in spermatozoa while maturing in a quiescent state prompts them to immensely dependent on epithelial cells for nutritional supports and information exchange. Thus, epididymal epithelial function and luminal microenviroment play crucial roles during epididymal spermatozoa maturation. We have previously reported that infertile male mice lacking the functional gene for epithelial tight-junction protein occludin resulted in impaired sperm lipid metabolism and defects in epididymal-dependent early embryo development. However, the underlying mechanism remains unclear. Our indepth study discovered that occludin promotes paracellular junctional endocytosis and luminal cholesterol clearance and lipid metabolism. This occludin-dependent junctional endocytosis involves the formation of double-membrane phagosomes from the epithelial apical paracellular membranes, which we called paraphagy. We found that paraphagy involves interactions of surface receptor FCGR2B and apical absorption of APOJ from the lumen. We propose that occludin-promoted paraphagy ensures epididymal function and sperm maturation, and the epididymal-dependent reproductive events including embryo development.
Funding Source: This work is supported by NNSFC (82071704), SMCST (19140903400), ShanghaiTech University, and University of Saint Joseph.
