Excessive ingestion of long-chain polyunsaturated fatty acids during developmental stage causes strain- and sex-dependent eye abnormalities in mice.
The eyes are rich in long-chain polyunsaturated fatty acids (LC-PUFAs) such as arachidonic acid [ARA; 20:4 (n-6)] and docosahexaenoic acid [DHA; 22:6 (n-3)]. Despite their abundance in the eyes, ARA and DHA cannot be sufficiently synthesized de novo in mammals. During gestation, eye development is exceptionally rapid, and substantial amounts of LC-PUFAs are needed to ensure proper eye development. Here, we studied the influences of dietary LC-PUFAs in dams (C57BL/6 and C3H/He) on the eye morphogenesis and organogenesis of their pups. Intriguingly, fetuses and newborn mice from C57BL/6 dams fed an LC-PUFA (particularly ARA)-enriched diet displayed a much higher incidence of eye abnormalities such as microphthalmia (small eye) and corneal opacity than those from dams fed an LC-PUFA-poor diet. The effects of LC-PUFAs on eye anomalies were evident only in the female pups of C57BL/6 inbred mice, not in those of C3H/He mice or male C57BL/6 mice. These results demonstrate a gene-by-environment (GxE) interaction in eye development in mice. Furthermore, our molecular analysis suggested the potential roles of Pitx3 and Pax6 in the above interaction involving ARA.
Laboratory for Molecular Psychiatry, RIKEN Brain Science Institute, Saitama 351-0198, Japan. mmaekawa@brain.riken.jp
Motoko
M
Maekawa
Yoshimi
Y
Iwayama
Akiko
A
Watanabe
Yayoi
Y
Nozaki
Tetsuo
T
Ohnishi
Hisako
H
Ohba
Manabu
M
Toyoshima
Kei
K
Hamazaki
Noriko
N
Osumi
Jun
J
Aruga
Takeo
T
Yoshikawa
D000818:Animals; D016718:Arachidonic Acid / Q000008:administration & dosage / Q000009:adverse effects*; D004032:Diet; D004281:Docosahexaenoic Acids / Q000008:administration & dosage / Q000009:adverse effects*; D004435:Eating; D005123:Eye / Q000187:drug effects* / Q000196:embryology; D005124:Eye Abnormalities / Q000139:chemically induced* / Q000235:genetics; D005136:Eye Proteins / Q000235:genetics; D005260:Female; D018398:Homeodomain Proteins / Q000235:genetics; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D000071841:PAX6 Transcription Factor; D051761:Paired Box Transcription Factors / Q000235:genetics; D012097:Repressor Proteins / Q000235:genetics; D012737:Sex Factors; D014157:Transcription Factors / Q000235:genetics
D005136:Eye Proteins; D018398:Homeodomain Proteins; D000071841:PAX6 Transcription Factor; D051761:Paired Box Transcription Factors; C000605732:Pax6 protein, mouse; D012097:Repressor Proteins; D014157:Transcription Factors; C433629:homeobox protein PITX3; D004281:Docosahexaenoic Acids; D016718:Arachidonic Acid