Golub Mari S, Hogrefe Casey E
Department of Environmental Toxicology and
California National Primate Research Center, University of California, Davis, Davis, CA.
J Nutr. 2015 Mar;145(3):647-53. doi: 10.3945/jn.114.201798. Epub 2014 Dec 24.
Anemia during the third trimester of fetal development affects one-third of the pregnancies in the United States and has been associated with postnatal behavioral outcomes. This study examines how fetal iron deficiency (ID) interacts with the fetal monoamine oxidase A (MAOA) genotype. MAOA metabolizes monoamine neurotransmitters. MAOA polymorphisms in humans affect temperament and modify the influence of early adverse environments on later behavior.
The aim of the study was to advance translation of developmental ID research in animal models by taking into account genetic factors that influence outcomes in human populations.
Male infant rhesus monkeys 3-4 mo old born to mothers fed an ID (10 ppm iron) diet were compared with controls (100 ppm iron). Infant monkeys with high- or low-transcription rate MAOA polymorphisms were equally distributed between diet groups. Behavioral responses to a series of structured experiences were recorded during a 25-h separation of the infants from their mothers.
Infant monkeys with low-transcription MAOA polymorphisms more clearly demonstrated the following ID effects suggested in earlier studies: a 4% smaller head circumference, a 39% lower cortisol response to social separation, a 129% longer engagement with novel visual stimuli, and 33% lesser withdrawal in response to a human intruder. The high MAOA genotype ID monkeys demonstrated other ID effects: less withdrawal and emotionality after social separation and lower "fearful" ratings.
MAOA × ID interactions support the role of monoamine neurotransmitters in prenatal ID effects in rhesus monkeys and the potential involvement of common human polymorphisms in determining the pattern of neurobehavioral effects produced by inadequate prenatal nutrition.
在美国，胎儿发育晚期的贫血影响三分之一的妊娠，并且与产后行为结果相关。本研究探讨胎儿缺铁（ID）如何与胎儿单胺氧化酶A（MAOA）基因型相互作用。MAOA代谢单胺类神经递质。人类中的MAOA多态性影响气质，并改变早期不良环境对后期行为的影响。
本研究的目的是通过考虑影响人类群体结果的遗传因素，推动动物模型中发育性ID研究的转化。
将喂食ID（10 ppm铁）饮食的母亲所生的3 - 4月龄雄性恒河猴婴儿与对照组（100 ppm铁）进行比较。具有高转录率或低转录率MAOA多态性的婴儿猴子在饮食组之间平均分配。在婴儿与母亲分离25小时期间，记录对一系列结构化经历的行为反应。
具有低转录MAOA多态性的婴儿猴子更清楚地表现出早期研究中提示的以下ID效应：头围小4%，对社会分离的皮质醇反应低39%，对新视觉刺激的接触时间长129%，对人类入侵者的退缩反应少33%。高MAOA基因型的ID猴子表现出其他ID效应：社会分离后退缩和情绪反应较少，“恐惧”评分较低。
MAOA×ID相互作用支持单胺类神经递质在恒河猴产前ID效应中的作用，以及常见人类多态性在确定产前营养不足所产生的神经行为效应模式中的潜在作用。
