PUBLICATION

Abnormal male reproduction and embryonic development induced by downregulation of a phospholipid fatty acid-introducing enzyme Lpgat1 in zebrafish

Authors
Shibata, T., Kawana, H., Nishino, Y., Ito, Y., Sato, H., Onishi, H., Kano, K., Inoue, A., Taketomi, Y., Murakami, M., Kofuji, S., Nishina, H., Miyazawa, A., Kono, N., Aoki, J.
ID
ZDB-PUB-220506-13
Date
2022
Source
Scientific Reports   12: 7312 (Journal)
Registered Authors
Nishina, Hiroshi
Keywords
none
MeSH Terms
  • 1-Acylglycerophosphocholine O-Acyltransferase/genetics
  • 1-Acylglycerophosphocholine O-Acyltransferase/metabolism
  • Acyltransferases/metabolism
  • Animals
  • Down-Regulation
  • Embryonic Development/genetics
  • Fatty Acids*/metabolism
  • Female
  • Male
  • Reproduction/genetics
  • Zebrafish*/genetics
  • Zebrafish*/metabolism
PubMed
35508627 Full text @ Sci. Rep.
Abstract
Phospholipids in the membrane consist of diverse pairs of fatty acids bound to a glycerol backbone. The biological significance of the diversity, however, remains mostly unclear. Part of this diversity is due to lysophospholipid acyltransferases (LPLATs), which introduce a fatty acid into lysophospholipids. The human genome has 14 LPLATs and most of them are highly conserved in vertebrates. Here, we analyzed the function of one of these enzymes, lysophosphatidylglycerol acyltransferase 1 (Lpgat1), in zebrafish. We found that the reproduction of heterozygous (lpgat1+/-) male mutants was abnormal. Crosses between heterozygous males and wild-type females produced many eggs with no obvious cleavage, whereas eggs produced by crosses between heterozygous females and wild-type males cleaved normally. Consistent with this, spermatozoa from heterozygous males had reduced motility and abnormal morphology. We also found that the occurrence of lpgat1 homozygous (lpgat1-/-) mutants was far lower than expected. In addition, downregulation of lpgat1 by morpholino antisense oligonucleotides resulted in severe developmental defects. Lipidomic analysis revealed that selective phospholipid species with stearic acid and docosahexaenoic acid were reduced in homozygous larvae and spermatozoa from heterozygotes. These results suggest that the specific phospholipid molecular species produced by Lpgat1 have an essential role in sperm fertilization and in embryonic development.
Genes / Markers
Figures
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Expression
Phenotype
Mutations / Transgenics
Human Disease / Model
Sequence Targeting Reagents
Fish
Antibodies
Orthology
Engineered Foreign Genes
Mapping