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.
Maekawa
Motoko
M
Laboratory for Molecular Psychiatry, RIKEN Brain Science Institute, Saitama 351-0198, Japan. mmaekawa@brain.riken.jp
Iwayama
Yoshimi
Y
Watanabe
Akiko
A
Nozaki
Yayoi
Y
Ohnishi
Tetsuo
T
Ohba
Hisako
H
Toyoshima
Manabu
M
Hamazaki
Kei
K
Osumi
Noriko
N
Aruga
Jun
J
Yoshikawa
Takeo
T
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