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 l...
| Main Authors: | , , , , , , , , , , , , , , |
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Nature Portfolio
2022-05-01
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| Series: | Scientific Reports |
| Online Access: | https://doi.org/10.1038/s41598-022-11002-4 |
| _version_ | 1828344430278475776 |
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| author | Takeaki Shibata Hiroki Kawana Yuri Nishino Yoshiko Ito Hiroyasu Sato Hirofumi Onishi Kuniyuki Kano Asuka Inoue Yoshitaka Taketomi Makoto Murakami Satoshi Kofuji Hiroshi Nishina Atsuo Miyazawa Nozomu Kono Junken Aoki |
| author_facet | Takeaki Shibata Hiroki Kawana Yuri Nishino Yoshiko Ito Hiroyasu Sato Hirofumi Onishi Kuniyuki Kano Asuka Inoue Yoshitaka Taketomi Makoto Murakami Satoshi Kofuji Hiroshi Nishina Atsuo Miyazawa Nozomu Kono Junken Aoki |
| author_sort | Takeaki Shibata |
| collection | DOAJ |
| description | 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. |
| first_indexed | 2024-04-13T23:57:10Z |
| format | Article |
| id | doaj.art-121df52d1e1a4756bdb7aee0adf128be |
| institution | Directory Open Access Journal |
| issn | 2045-2322 |
| language | English |
| last_indexed | 2024-04-13T23:57:10Z |
| publishDate | 2022-05-01 |
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| series | Scientific Reports |
| spelling | doaj.art-121df52d1e1a4756bdb7aee0adf128be2022-12-22T02:23:51ZengNature PortfolioScientific Reports2045-23222022-05-0112111210.1038/s41598-022-11002-4Abnormal male reproduction and embryonic development induced by downregulation of a phospholipid fatty acid-introducing enzyme Lpgat1 in zebrafishTakeaki Shibata0Hiroki Kawana1Yuri Nishino2Yoshiko Ito3Hiroyasu Sato4Hirofumi Onishi5Kuniyuki Kano6Asuka Inoue7Yoshitaka Taketomi8Makoto Murakami9Satoshi Kofuji10Hiroshi Nishina11Atsuo Miyazawa12Nozomu Kono13Junken Aoki14Department of Health Chemistry, Graduate School of Pharmaceutical Sciences, The University of TokyoDepartment of Health Chemistry, Graduate School of Pharmaceutical Sciences, The University of TokyoGraduate School of Science, University of HyogoGraduate School of Science, University of HyogoLaboratory of Microenvironmental and Metabolic Health Science, Center for Disease Biology and Integrative Medicine, Graduate School of Medicine, The University of TokyoDepartment of Health Chemistry, Graduate School of Pharmaceutical Sciences, The University of TokyoDepartment of Health Chemistry, Graduate School of Pharmaceutical Sciences, The University of TokyoLaboratory of Molecular & Cellular Biochemistry, Graduate School of Pharmaceutical Sciences, Tohoku UniversityLaboratory of Microenvironmental and Metabolic Health Science, Center for Disease Biology and Integrative Medicine, Graduate School of Medicine, The University of TokyoLaboratory of Microenvironmental and Metabolic Health Science, Center for Disease Biology and Integrative Medicine, Graduate School of Medicine, The University of TokyoDepartment of Developmental and Regenerative Biology, Medical Research Institute, Tokyo Medical and Dental University, Tokyo, JapanDepartment of Developmental and Regenerative Biology, Medical Research Institute, Tokyo Medical and Dental University, Tokyo, JapanGraduate School of Science, University of HyogoDepartment of Health Chemistry, Graduate School of Pharmaceutical Sciences, The University of TokyoDepartment of Health Chemistry, Graduate School of Pharmaceutical Sciences, The University of TokyoAbstract 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.https://doi.org/10.1038/s41598-022-11002-4 |
| spellingShingle | Takeaki Shibata Hiroki Kawana Yuri Nishino Yoshiko Ito Hiroyasu Sato Hirofumi Onishi Kuniyuki Kano Asuka Inoue Yoshitaka Taketomi Makoto Murakami Satoshi Kofuji Hiroshi Nishina Atsuo Miyazawa Nozomu Kono Junken Aoki Abnormal male reproduction and embryonic development induced by downregulation of a phospholipid fatty acid-introducing enzyme Lpgat1 in zebrafish Scientific Reports |
| title | Abnormal male reproduction and embryonic development induced by downregulation of a phospholipid fatty acid-introducing enzyme Lpgat1 in zebrafish |
| title_full | Abnormal male reproduction and embryonic development induced by downregulation of a phospholipid fatty acid-introducing enzyme Lpgat1 in zebrafish |
| title_fullStr | Abnormal male reproduction and embryonic development induced by downregulation of a phospholipid fatty acid-introducing enzyme Lpgat1 in zebrafish |
| title_full_unstemmed | Abnormal male reproduction and embryonic development induced by downregulation of a phospholipid fatty acid-introducing enzyme Lpgat1 in zebrafish |
| title_short | Abnormal male reproduction and embryonic development induced by downregulation of a phospholipid fatty acid-introducing enzyme Lpgat1 in zebrafish |
| title_sort | abnormal male reproduction and embryonic development induced by downregulation of a phospholipid fatty acid introducing enzyme lpgat1 in zebrafish |
| url | https://doi.org/10.1038/s41598-022-11002-4 |
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