title: Polyunsaturated fatty acids are incorporated into maturating male mouse germ cells by lysophosphatidic acid acyltransferase 3.
abstract: Long-chain polyunsaturated fatty acids (PUFAs) accumulate in mammalian testis during puberty and are essential for fertility. To investigate whether lysophospholipid acyltransferases determine the PUFA composition of testicular phospholipids during pubertal development, we compared their mRNA expression, in vitro activity, and specificity with the lipidomic profile of major phospholipids. The accumulation of PUFAs in phosphatidylcholine, phosphatidylethanolamine, and phosphatidylserine correlated with an induced lysophosphatidic acid acyltransferase (LPAAT)3 mRNA expression, increased microsomal LPAAT3 activity, and shift of LPAAT specificity to PUFA-coenzyme A. LPAAT3 was induced during germ cell maturation, as shown by immunofluorescence microscopy. Accordingly, differentiation of mouse GC-2spd(ts) spermatocytes into spermatides up-regulated LPAAT3 mRNA, increased the amount of polyunsaturated phospholipids, and shifted the specificity for the incorporation of deuterium-labeled docosahexaenoic acid toward phosphatidylcholine and phosphatidylethanolamine. Stable knockdown of LPAAT3 in GC-2spd(ts) cells significantly decreased microsomal LPAAT3 activity, reduced levels of polyunsaturated phosphatidylethanolamine species, and impaired cell proliferation/survival during geneticin selection. We conclude that the induction of LPAAT3 during germ cell development critically contributes to the accumulation of PUFAs in testicular phospholipids, thereby possibly affecting sperm cell production.
authors.affiliation: Department of Biochemistry and Molecular Biology, University of Tokyo, Bunkyo-ku, Tokyo, Japan.
authors.forename: Andreas
authors.initials: A
authors.lastname: Koeberle
authors.forename: Hideo
authors.initials: H
authors.lastname: Shindou
authors.forename: Takeshi
authors.initials: T
authors.lastname: Harayama
authors.forename: Koichi
authors.initials: K
authors.lastname: Yuki
authors.forename: Takao
authors.initials: T
authors.lastname: Shimizu
mesh_terms: D000217:Acyltransferases / Q000235:genetics / Q000378:metabolism*; D000367:Age Factors; D000818:Animals; D005231:Fatty Acids, Unsaturated / Q000378:metabolism*; D008297:Male; D008560:Membrane Fluidity / Q000502:physiology; D051379:Mice; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D008861:Microsomes / Q000201:enzymology; D010713:Phosphatidylcholines / Q000378:metabolism; D010714:Phosphatidylethanolamines / Q000378:metabolism; D010718:Phosphatidylserines / Q000378:metabolism; D012333:RNA, Messenger / Q000378:metabolism; D013087:Spermatids / Q000166:cytology / Q000201:enzymology; D013090:Spermatocytes / Q000166:cytology / Q000201:enzymology; D013093:Spermatogonia / Q000166:cytology / Q000201:enzymology; D013094:Spermatozoa / Q000166:cytology / Q000201:enzymology*; D013737:Testis / Q000166:cytology / Q000378:metabolism
chemical_list: D005231:Fatty Acids, Unsaturated; D010713:Phosphatidylcholines; D010714:Phosphatidylethanolamines; D010718:Phosphatidylserines; D012333:RNA, Messenger; D000217:Acyltransferases; C018764:2-acylglycerophosphate acyltransferase