TY - JOUR
T1 - Acyl-CoA synthetase 6 regulates long-chain polyunsaturated fatty acid composition of membrane phospholipids in spermatids and supports normal spermatogenic processes in mice
AU - Shishikura, Kyosuke
AU - Kuroha, Sayoko
AU - Matsueda, Shinnosuke
AU - Iseki, Hachiro
AU - Matsui, Takeshi
AU - Inoue, Azusa
AU - Arita, Makoto
N1 - Funding Information:
This study was supported by the Japan Society for the Promotion of Science (JSPS) Grants-in-Aid for Scientific Research (KAKENHI; JP15H05897, 15H05898, and 15H04648 to M.A.), and Riken Junior Research Associate Program (to K.S.). The authors thank T. Ogawa (Yokohama City University Association of Medical Science) for constructive comments on the research, and K. Toyooka (Science Technology Platform Division, Center for Sustainable Resource, Riken) for technical support for the FE-SEM analyses, and all the members of the M.A. laboratory and the Laboratory for Developmental Genetics (Riken Center for Integrative Medical Sciences) for technical support for the histological analysis. The authors also thank the staff at BioMed Proofreading, LLC (Cleveland, OH, USA) for help with the English translation of the manuscript. The authors declare no conflicts of interest.
Publisher Copyright:
© FASEB.
PY - 2019/12
Y1 - 2019/12
N2 - Long-chain polyunsaturated fatty acids (LCPUFAs), such as docosahexaenoic acid (DHA, 22:6) and docosapentaenoic acid (DPA, 22:5), have versatile physiologic functions. Studies have suggested that DHA and DPA are beneficial for maintaining sperm quality. However, their mechanisms of action are still unclear because of the poor understanding of DHA/DPA metabolism in the testis. DHA and DPA are mainly stored as LCPUFA-containing phospholipids and support normal spermatogenesis. Long-chain acyl-conenzyme A (CoA) synthetase (ACSL) 6 is an enzyme that preferentially converts LCPUFA into LCPUFA-CoA. Here, we report that ACSL6 knockout (KO) mice display severe male infertility due to attenuated sperm numbers and function. ACSL6 is highly expressed in differentiating spermatids, and ACSL6 KO mice have reduced LCPUFA-containing phospholipids in their spermatids. Delayed sperm release and apoptosis of differentiated spermatids were observed in these mice. The results of this study indicate that ACSL6 contributes to the local accumulation of DHA- and DPA-containing phospholipids in spermatids to support normal spermatogenesis.—Shishikura, K., Kuroha, S., Matsueda, S., Iseki, H., Matsui, T., Inoue, A., Arita, M. Acyl-CoA synthetase 6 regulates long-chain polyunsaturated fatty acid composition of membrane phospholipids in spermatids and supports normal spermatogenic processes in mice. FASEB J. 33, 14194-14203 (2019). www.fasebj.org.
AB - Long-chain polyunsaturated fatty acids (LCPUFAs), such as docosahexaenoic acid (DHA, 22:6) and docosapentaenoic acid (DPA, 22:5), have versatile physiologic functions. Studies have suggested that DHA and DPA are beneficial for maintaining sperm quality. However, their mechanisms of action are still unclear because of the poor understanding of DHA/DPA metabolism in the testis. DHA and DPA are mainly stored as LCPUFA-containing phospholipids and support normal spermatogenesis. Long-chain acyl-conenzyme A (CoA) synthetase (ACSL) 6 is an enzyme that preferentially converts LCPUFA into LCPUFA-CoA. Here, we report that ACSL6 knockout (KO) mice display severe male infertility due to attenuated sperm numbers and function. ACSL6 is highly expressed in differentiating spermatids, and ACSL6 KO mice have reduced LCPUFA-containing phospholipids in their spermatids. Delayed sperm release and apoptosis of differentiated spermatids were observed in these mice. The results of this study indicate that ACSL6 contributes to the local accumulation of DHA- and DPA-containing phospholipids in spermatids to support normal spermatogenesis.—Shishikura, K., Kuroha, S., Matsueda, S., Iseki, H., Matsui, T., Inoue, A., Arita, M. Acyl-CoA synthetase 6 regulates long-chain polyunsaturated fatty acid composition of membrane phospholipids in spermatids and supports normal spermatogenic processes in mice. FASEB J. 33, 14194-14203 (2019). www.fasebj.org.
KW - ACSL6
KW - docosahexaenoic acid
KW - docosapentaenoic acid
KW - testis
UR - http://www.scopus.com/inward/record.url?scp=85075958050&partnerID=8YFLogxK
UR - http://www.scopus.com/inward/citedby.url?scp=85075958050&partnerID=8YFLogxK
U2 - 10.1096/fj.201901074R
DO - 10.1096/fj.201901074R
M3 - Article
C2 - 31648559
AN - SCOPUS:85075958050
SN - 0892-6638
VL - 33
SP - 14194
EP - 14203
JO - FASEB Journal
JF - FASEB Journal
IS - 12
ER -