Dataset Information

Fetal iron deficiency and genotype influence emotionality in infant rhesus monkeys.

ABSTRACT:

Background

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.

Objective

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.

Methods

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.

Results

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.

Conclusion

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.

SUBMITTER: Golub MS

PROVIDER: S-EPMC4336538 | biostudies-literature | 2015 Mar

REPOSITORIES: biostudies-literature

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Publications

Fetal iron deficiency and genotype influence emotionality in infant rhesus monkeys.

Golub Mari S MS Hogrefe Casey E CE

The Journal of nutrition 20141224 3

<h4>Background</h4>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.<h4>Objective</h4>The aim of ...[more]

PMID: 25733484

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Project description:BackgroundIron deficiency is the most common nutrient deficiency in human infants aged 6 to 24 mo, and negatively affects many cellular metabolic processes, including energy production, electron transport, and oxidative degradation of toxins. There can be persistent influences on long-term metabolic health beyond its acute effects.ObjectivesThe objective was to determine how iron deficiency in infancy alters the serum metabolomic profile and to test whether these effects persist after the resolution of iron deficiency in a nonhuman primate model of spontaneous iron deficiency.MethodsBlood was collected from naturally iron-sufficient (IS; n = 10) and iron-deficient (ID; n = 10) male and female infant rhesus monkeys (Macaca mulatta) at 6 mo of age. Iron deficiency resolved without intervention upon feeding of solid foods, and iron status was re-evaluated at 12 mo of age from the IS and formerly ID monkeys using hematological and other indices; sera were metabolically profiled using HPLC/MS and GC/MS with isobaric standards for identification and quantification at both time points.ResultsA total of 413 metabolites were measured, with differences in 40 metabolites identified between IS and ID monkeys at 6 mo (P$\le $ 0.05). At 12 mo, iron-related hematological parameters had returned to normal, but the formerly ID infants remained metabolically distinct from the age-matched IS infants, with 48 metabolites differentially expressed between the groups. Metabolomic profiling indicated altered liver metabolites, differential fatty acid production, increased serum uridine release, and atypical bile acid production in the ID monkeys.ConclusionsPathway analyses of serum metabolites provided evidence of a hypometabolic state, altered liver function, differential essential fatty acid production, irregular uracil metabolism, and atypical bile acid production in ID infants. Many metabolites remained altered after the resolution of ID, suggesting long-term effects on metabolic health.

Project description:Temperament is a construct whose manifestations are quantifiable from an early age, and whose origins have been proposed as "biological." Our goal was to determine whether maternal rank and infant genotype are associated with five measures of temperament in 3- to 4-month old rhesus monkeys (Macaca mulatta), all of whom were born and reared by their mothers in large, outdoor, half-acre cages. Maternal rank was defined as the proportion of animals outranked by each female, and the two genes of interest to us were monoamine oxidase and serotonin transporter, both of which are polymorphic in their promoter regions (MAOA-LPR and 5-HTTLPR, respectively), with one allele of each gene considered a "plasticity" allele, conferring increased sensitivity to environmental events. Our large sample size (n = 2014-3140) enabled us to examine the effects of individual genotypes rather than combining genotypes as is often done. Rank was positively associated with Confident temperament, but only for animals with the 5-repeat allele for MAOA-LPR. Rank had no other effect on temperament. In contrast, genotype had many different effects, with 5-HTTLPR associated with behavioral inhibition, and MAOA-LPR associated with ratings-based measures of temperament. We also examined the joint effect of the two genotypes and found some evidence for a dose-response: animals with the plasticity alleles for both genes were more likely to be behaviorally inhibited. Our results suggest phenotypic differences between animals possessing alleles for MAOA-LPR that show functional equivalence based on in vitro tests, and our data for 5-HTTLPR revealed differences between short/short homozygotes and long/short heterozygotes, strongly suggesting that combining genotypes for statistical analysis should be avoided if possible. Our analysis also provides evidence of sex differences in temperament, and, to our knowledge, the only evidence of differences in temperament based on specific pathogen-free status. We suggest several directions for future research.

Project description:Dual-focus lenses that impose simultaneous competing myopic defocus over the entire visual field produce axial hyperopic shifts in refractive error. The purpose of this study was to characterize the effects of eccentricity on the ability of myopic defocus signals to influence central refractive development in infant monkeys. From 24 to 152 days of age, rhesus monkeys were reared with binocular, dual-focus lenses that had central, zero-powered zones surrounded by alternating concentric annular power zones of +3D and zero power. Between subject groups the diameter of the central, zero-powered zone was varied from 2 mm to 8 mm in 2 mm steps (+3D/pl 2 mm, n = 6; +3D/pl 4 mm, n = 6; +3D/pl 6 mm, n = 8, or + 3D/pl 8 mm, n = 6). For the treatment lens with 2, 4, 6 and 8 mm central zones, objects at eccentricities beyond 11°, 16°, 19° and 23°, respectively, were imaged exclusively through the dual-power peripheral zones. Refractive status (retinoscopy), corneal power (keratometry) and axial dimensions (ultrasonography) were measured at two-week intervals. Comparison data were obtained from monkeys reared with binocular, single-vision +3D full-field lenses (+3D FF, n = 6) and 41 normal control monkeys reared with unrestricted vision. At the end of the rearing period, with the exception of the +3D/pl 8 mm group (median = +3.64 D), the ametropias for the other lens-reared groups (medians: FF = +4.39 D, 2 mm = +5.19 D, 4 mm = +5.59 D, 6 mm = +3.50 D) were significantly more hyperopic than that for the normal monkeys (+2.50 D). These hyperopic errors were associated with shallower vitreous chambers. The key finding was that the extent and consistency of these hyperopic ametropias varied with the eccentricity of the dual-focus zones. The results confirm that myopic defocus in the near periphery can slow axial growth, but that imposed defocus beyond about 20° from the fovea does not consistently alter central refractive development.

Dataset Information

Fetal iron deficiency and genotype influence emotionality in infant rhesus monkeys.

Background

Objective

Methods

Results

Conclusion

Publications

Fetal iron deficiency and genotype influence emotionality in infant rhesus monkeys.

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