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GEO help: Mouse over screen elements for information. |
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| Status |
Public on Nov 07, 2022 |
| Title |
Epididymal epithelial degeneration and lipid metabolism impairment account for male infertility in occludin knockout mice |
| Organism |
Mus musculus |
| Experiment type |
Expression profiling by high throughput sequencing
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| Summary |
Occludin (OCLN) is a tight junction protein and Ocln deletion mutation causes male infertility in mice. However, the role of OCLN in male reproductive system remains unknown. In this study, we found defective proximal epididymis in Ocln-null mice with impaired sperm motility and fertilization, but no defects in testicular spermatogenesis. Integrative omics analysis revealed the downregulation of gene clusters enriched in acid secretion and fatty acid metabolism in the Ocln-null epididymis, especially the enzymes related to the unsaturated arachidonic acid pathway. The number of proton-pump V-ATPase-expression clear cells, a key player of luminal acidification in the epididymis, declined drastically from prepubertal age before sperm arrival but not in the early postnatal-age. This was accompanied by clear cell apoptosis and increase in pH in the epididymal fluid of OCLN-deficient mice. The lipidomics results showed significantly increased levels of specific DAGs conjugated to unsaturated fatty acids in the Ocln-mutant. Immunofluorescent labeling showed that the arachidonic acid converting enzyme PTGDS and phospholipase PLA2g12a were prominently altered in the principal cells and luminal contents of the Ocln-mutant epididymis. Whereas the carboxylate ester lipase CES1, originally enriched in the WT basal cells, was found upregulated in the Ocln-mutant principal cells. Overall, this study demonstrates that OCLN is essential for maintaining the survival of acid-secreting clear cells and unsaturated fatty acid catabolism in the mouse epididymis, as well as ensuring sperm maturation and male fertility.
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| Overall design |
mRNA profiles of whole epididymis of adult wild type (WT) and Ocln-/- mice were generated by deep sequencing, in triplicate, using Illumina HiSeq X Ten.
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| Contributor(s) |
Shum W, Zhang B, Liu B, Gao D |
| Citation(s) |
36518247 |
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| Submission date |
Feb 04, 2021 |
| Last update date |
Jan 06, 2023 |
| Contact name |
Winnie Shum |
| Organization name |
ShanghaiTech University
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| Street address |
393 Hua Xia Middle Rd. Pudong District
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| City |
Shanghai |
| ZIP/Postal code |
201210 |
| Country |
China |
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| Platforms (1) |
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| Samples (6)
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| Relations |
| BioProject |
PRJNA699449 |
| SRA |
SRP304697 |
| Supplementary file |
Size |
Download |
File type/resource |
| GSE166141_All.counts_wholeEpi.txt.gz |
438.2 Kb |
(ftp)(http) |
TXT |
SRA Run Selector |
| Raw data are available in SRA |
| Processed data are available on Series record |
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