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

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 lysophosph...

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Autores principales: Shibata, Takeaki, Kawana, Hiroki, Nishino, Yuri, Ito, Yoshiko, Sato, Hiroyasu, Onishi, Hirofumi, Kano, Kuniyuki, Inoue, Asuka, Taketomi, Yoshitaka, Murakami, Makoto, Kofuji, Satoshi, Nishina, Hiroshi, Miyazawa, Atsuo, Kono, Nozomu, Aoki, Junken
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Nature Publishing Group UK 2022
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9068807/
https://www.ncbi.nlm.nih.gov/pubmed/35508627
http://dx.doi.org/10.1038/s41598-022-11002-4
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author Shibata, Takeaki
Kawana, Hiroki
Nishino, Yuri
Ito, Yoshiko
Sato, Hiroyasu
Onishi, Hirofumi
Kano, Kuniyuki
Inoue, Asuka
Taketomi, Yoshitaka
Murakami, Makoto
Kofuji, Satoshi
Nishina, Hiroshi
Miyazawa, Atsuo
Kono, Nozomu
Aoki, Junken
author_facet Shibata, Takeaki
Kawana, Hiroki
Nishino, Yuri
Ito, Yoshiko
Sato, Hiroyasu
Onishi, Hirofumi
Kano, Kuniyuki
Inoue, Asuka
Taketomi, Yoshitaka
Murakami, Makoto
Kofuji, Satoshi
Nishina, Hiroshi
Miyazawa, Atsuo
Kono, Nozomu
Aoki, Junken
author_sort Shibata, Takeaki
collection PubMed
description 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.
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spelling pubmed-90688072022-05-05 Abnormal male reproduction and embryonic development induced by downregulation of a phospholipid fatty acid-introducing enzyme Lpgat1 in zebrafish Shibata, Takeaki Kawana, Hiroki Nishino, Yuri Ito, Yoshiko Sato, Hiroyasu Onishi, Hirofumi Kano, Kuniyuki Inoue, Asuka Taketomi, Yoshitaka Murakami, Makoto Kofuji, Satoshi Nishina, Hiroshi Miyazawa, Atsuo Kono, Nozomu Aoki, Junken Sci Rep Article 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. Nature Publishing Group UK 2022-05-04 /pmc/articles/PMC9068807/ /pubmed/35508627 http://dx.doi.org/10.1038/s41598-022-11002-4 Text en © The Author(s) 2022 https://creativecommons.org/licenses/by/4.0/Open Access This article is licensed under a Creative Commons Attribution 4.0 International License, which permits use, sharing, adaptation, distribution and reproduction in any medium or format, as long as you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons licence, and indicate if changes were made. The images or other third party material in this article are included in the article's Creative Commons licence, unless indicated otherwise in a credit line to the material. If material is not included in the article's Creative Commons licence and your intended use is not permitted by statutory regulation or exceeds the permitted use, you will need to obtain permission directly from the copyright holder. To view a copy of this licence, visit http://creativecommons.org/licenses/by/4.0/ (https://creativecommons.org/licenses/by/4.0/) .
spellingShingle Article
Shibata, Takeaki
Kawana, Hiroki
Nishino, Yuri
Ito, Yoshiko
Sato, Hiroyasu
Onishi, Hirofumi
Kano, Kuniyuki
Inoue, Asuka
Taketomi, Yoshitaka
Murakami, Makoto
Kofuji, Satoshi
Nishina, Hiroshi
Miyazawa, Atsuo
Kono, Nozomu
Aoki, Junken
Abnormal male reproduction and embryonic development induced by downregulation of a phospholipid fatty acid-introducing enzyme Lpgat1 in zebrafish
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
topic Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9068807/
https://www.ncbi.nlm.nih.gov/pubmed/35508627
http://dx.doi.org/10.1038/s41598-022-11002-4
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