Fetal sex modulates placental microRNA expression, potential microRNA-mRNA interactions, and levels of amino acid transporter expression and substrates: INFAT study subpopulation analysis of n-3 LCPUFA intervention during pregnancy and associations with offspring body composition.

BACKGROUND: Previously, we revealed sexually dimorphic mRNA expression and responsiveness to maternal dietary supplementation with n-3 long-chain polyunsaturated fatty acids (LCPUFA) in placentas from a defined INFAT study subpopulation. Here, we extended these analyses and explored the respective placental microRNA expression, putative microRNA-mRNA interactions, and downstream target processes as well as their associations with INFAT offspring body composition. RESULTS: We performed explorative placental microRNA profiling, predicted microRNA-mRNA interactions by bioinformatics, validated placental target microRNAs and their putative targets by RT-qPCR and western blotting, and measured amino acid levels in maternal and offspring cord blood plasma and placenta. microRNA, mRNA, protein, and amino acid levels were associated with each other and with offspring body composition from birth to 5 years of age. Forty-six differentially regulated microRNAs were found. Validations identified differential expression for microRNA-99a (miR-99a) and its predicted target genes mTOR, SLC7A5, encoding L-type amino acid transporter 1 (LAT1), and SLC6A6, encoding taurine transporter (TauT), and their prevailing significant sexually dimorphic regulation. Target mRNA levels were mostly higher in placentas from control male than from female offspring, whereas respective n-3 LCPUFA responsive target upregulation was predominantly found in female placentas, explaining the rather balanced expression levels between the sexes present only in the intervention group. LAT1 and TauT substrates tryptophan and taurine, respectively, were significantly altered in both maternal plasma at 32 weeks' gestation and cord plasma following intervention, but not in the placenta. Several significant associations were observed for miR-99a, mTOR mRNA, SLC7A5 mRNA, and taurine and tryptophan in maternal and cord plasma with offspring body composition at birth, 1 year, 3 and 5 years of age. CONCLUSIONS: Our data suggest that the analyzed targets may be part of a sexually dimorphic molecular regulatory network in the placenta, possibly modulating gene expression per se and/or counteracting n-3 LCPUFA responsive changes, and thereby stabilizing respective placental and fetal amino acid levels. Our data propose placental miR-99, SLC7A5 mRNA, and taurine and tryptophan levels in maternal and fetal plasma as potentially predictive biomarkers for offspring body composition.

Cord blood and child plasma adiponectin levels in relation to childhood obesity risk and fat distribution up to 5 y.

BACKGROUND: Few human studies have explored the role of adiponectin in early life on growth and adipose tissue development. METHODS: High molecular weight (HMW) and total adiponectin levels from 141 cord blood samples and plasma blood samples from 40 3-y-old children were analyzed. Associations between adiponectin levels in cord blood and child plasma, and infant/child growth and fat mass measurements up to the age of 5 y were assessed using linear regression models. RESULTS: HMW cord blood adiponectin was positively associated with weight, BMI percentiles, and lean body mass at birth only. At 3 and 4 y, positive associations were found with cord blood adiponectin and sum of four skinfold thickness measures and percentage of body fat following adjustment for maternal and child covariates, but did not persist at 5 y. There was no significant evidence of an association between child plasma HMW adiponectin and growth or body composition characteristics at 3-5 y. CONCLUSION: Our results do not support the hypothesis that HMW cord blood adiponectin is a useful biomarker for the prediction of adiposity at the age of 5 y. Additionally, there is no evidence that plasma HMW adiponectin levels predict body fat distribution between 3-5 y.