Autophagy core protein ATG5 is required for elongating spermatid development, sperm individualization and normal fertility in male mice.

Autophagy
Qian HuangZhibing Zhang

Abstract

Spermiogenesis is the longest phase of spermatogenesis, with dramatic morphological changes and a final step of spermiation, which involves protein degradation and the removal of excess cytoplasm; therefore, we hypothesized that macroautophagy/autophagy might be involved in the process. To test this hypothesis, we examined the function of ATG5, a core autophagy protein in male germ cell development. Floxed Atg5 and Stra8- iCre mice were crossed to conditionally inactivate Atg5 in male germ cells. In Atg5flox/flox; Stra8- iCre mutant mice, testicular expression of the autophagosome marker LC3A/B-II was significantly reduced, and expression of autophagy receptor SQSTM1/p62 was significantly increased, indicating a decrease in testicular autophagy activity. The fertility of mutant mice was dramatically reduced with about 70% being infertile. Sperm counts and motility were also significantly reduced compared to controls. Histological examination of the mutant testes revealed numerous, large residual bodies in the lumen of stages after their normal resorption within the seminiferous epithelium. The cauda epididymal lumen was filled with sloughed germ cells, large cytoplasmic bodies, and spermatozoa with disorganized heads and tails....Continue Reading

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Citations

Jun 3, 2021·Mammalian Genome : Official Journal of the International Mammalian Genome Society·Basit ShahQinghua Shi
Jun 17, 2021·Biology of Reproduction·Wenfeng XiongZhugang Wang
Aug 13, 2021·Stem Cell Research & Therapy·Qingyin LinYanzhou Yang

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Methods Mentioned

BETA
electron microscopy
confocal microscopy
protein assay
PCRs
neddylation
PCR
scanning electron microscopy
light microscopy
genotyping

Software Mentioned

Pinnacle Studio HD
MTrackJ
ImageJ

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