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

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.

Identification and characterization of LPLAT7 as an sn-1-specific lysophospholipid acyltransferase

“…established zebrafish mutants of LPLAT7/LPGAT1 and showed that they had decreased levels of C18:0-containing PC and PE and increased levels of C16:0-containing PC and PE. PG species were not affected in the lplat7 / lpgat1 mutant zebrafish ( 23 ).…”

Overexpression of lysophospholipid acyltransferase, LPLAT10/LPCAT4/LPEAT2, in the mouse liver increases glucose‐stimulated insulin secretion

“…The diversity of phospholipids due to variations in the polar head group and fatty acids, as determined by LPLATs, has been reported 39,[46][47][48] ; however, phospholipid profiles determined by LPLAT10 in vivo have not been elucidated. Our study is the first to reveal PC and LPC profiles determined by LPLAT10 in the mouse liver using an Ad vector-mediated overexpression system.…”

Per- and Polyfluoroalkyl Substances: Impacts on Morphology, Behavior and Lipid Levels in Zebrafish Embryos

“…PS signaling and recognition by receptors are essential for normal zebrafish embryo development [ 90 ] and studies have shown that dysregulation of PS levels can be associated with morphological malformations similar to those seen in this study. Shibata et al [ 91 ] found that downregulation of lysophosphatidylglycerol acyltransferase 1 resulted in decreases in various phospholipids, including PS, that coincided with developmental malformations in zebrafish, including bent embryo axis (spinal curvature). Dysregulation of phosphatidylserine synthase (PSS), which catalyzes the production of PS, has been linked to skeletal malformations in humans and severe angulation of the trunk (spinal curvature) in zebrafish [ 92 ].…”