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Sex-specific associations between placental leptin promoter DNA methylation and infant neurobehavior.

ABSTRACT: Leptin (LEP) is a hormone central for energy homeostasis and has been implicated in neurodevelopment. This adipokine is produced by the placenta and is epigenetically regulated by promoter DNA methylation. Recent evidence has suggested a role for LEP in behavioral development. In this study, we investigated associations between profiles of human newborn neurobehavior and placental LEP DNA methylation.We determined LEP promoter methylation in 444 placental samples from healthy term infants and measured LEP gene expression in a random subset of these samples. Infant neurobehavior was assessed with the NICU Network Neurobehavioral Scales (NNNS) and we examined the relationship between LEP promoter methylation and profiles of infant neurobehavior derived from these scores generated using a hierarchical model-based clustering method.LEP methylation is negatively correlated with gene expression only in placentas from male infants (r=-0.6, P=0.006). A 10% increase in LEP DNA methylation was associated with membership in a profile of infant neurobehavior marked by increased lethargy and hypotonicity (OR=1.9; 95% CI: 1.07-3.4), and consistently with reduced risk of membership in a profile characterized by decreased lethargy and hypotonicity (OR=0.54; 95% CI: 0.3-0.94) only in male infants (n=223). No statistically significant associations were observed amongst female infants.These results suggest that increased placental LEP DNA methylation, related to reduced expression, may play a role in human newborn neurodevelopment, particularly in reactivity to various stimuli, but that these effects may be sexually dimorphic.

SUBMITTER: Lesseur C

PROVIDER: S-EPMC3912462 | biostudies-literature | 2014 Feb

REPOSITORIES: biostudies-literature

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Sex-specific associations between placental leptin promoter DNA methylation and infant neurobehavior.

Lesseur Corina C Armstrong David A DA Murphy Megan A MA Appleton Allison A AA Koestler Devin C DC Paquette Alison G AG Lester Barry M BM Marsit Carmen J CJ

Psychoneuroendocrinology 20131030

<h4>Background</h4>Leptin (LEP) is a hormone central for energy homeostasis and has been implicated in neurodevelopment. This adipokine is produced by the placenta and is epigenetically regulated by promoter DNA methylation. Recent evidence has suggested a role for LEP in behavioral development. In this study, we investigated associations between profiles of human newborn neurobehavior and placental LEP DNA methylation.<h4>Methods</h4>We determined LEP promoter methylation in 444 placental sampl ...[more]

PMID: 24485470

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Project description:Background: Placental malaria (PM) has been associated with a higher risk of malaria during infancy. However, it is unclear whether this association is causal, and is modified by infant sex, and whether intermittent preventive treatment in pregnancy (IPTp) can reduce infant malaria by preventing PM.Methods: Data from a birth cohort of 656 infants born to HIV-uninfected mothers randomised to IPTp with dihydroartemisinin-piperaquine (DP) or Sulfadoxine-pyrimethamine (SP) was analysed. PM was categorized as no PM, active PM (presence of parasites), mild-moderate past PM (>?0-20% high powered fields [HPFs] with pigment), or severe past PM (>?20% HPFs with pigment). The association between PM and incidence of malaria in infants stratified by infant sex was examined. Causal mediation analysis was used to test whether IPTp can impact infant malaria incidence via preventing PM.Results: There were 1088 malaria episodes diagnosed among infants during 596.6 person years of follow-up. Compared to infants born to mothers with no PM, the incidence of malaria was higher among infants born to mothers with active PM (adjusted incidence rate ratio [aIRR] 1.30, 95% CI 1.00-1.71, p?=?0.05) and those born to mothers with severe past PM (aIRR 1.28, 95% CI 0.89-1.83, p?=?0.18), but the differences were not statistically significant. However, when stratifying by infant sex, compared to no PM, severe past PM was associated a higher malaria incidence in male (aIRR 2.17, 95% CI 1.45-3.25, p?<?0.001), but not female infants (aIRR 0.74, 95% CI 0.46-1.20, p?=?0.22). There were no significant associations between active PM or mild-moderate past PM and malaria incidence in male or female infants. Male infants born to mothers given IPTp with DP had significantly less malaria in infancy than males born to mothers given SP, and 89.7% of this effect was mediated through prevention of PM.Conclusion: PM may have more severe consequences for male infants, and interventions which reduce PM could mitigate these sex-specific adverse outcomes. More research is needed to better understand this sex-bias between PM and infant malaria risk. Trial registration ClinicalTrials.gov, NCT02793622. Registered 8 June 2016, https://clinicaltrials.gov/ct2/show/NCT02793622.

Dataset Information

Sex-specific associations between placental leptin promoter DNA methylation and infant neurobehavior.

Publications

Sex-specific associations between placental leptin promoter DNA methylation and infant neurobehavior.

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