Lipid mediator profile in vernix caseosa reflects skin barrier development

Abstract

Vernix caseosa (VC) is a protective layer that covers the skin of most human newborns. This study characterized the VC lipid mediator profile, and examined its relationship to gestational period, gender of the newborn and maternal lifestyle. VC collected at birth from 156 newborns within the ALADDIN birth cohort was analyzed and 3 different groups of lipid mediators (eicosanoids and related oxylipin analogs, endocannabinoids and sphingolipids) were screened using LC-MS/MS. A total of 54 compounds were detected in VC. A number of associations between lipid mediators and the gestational period were observed, including increases in the ceramide to sphingomyelin ratio as well as the endocannabinoids anandamide and 2-arachidonoylglycerol. Gender-specific differences in lipid mediator levels were observed for all 3 lipid classes. In addition, levels of the linoleic acid oxidation products 9(10)-epoxy-12Z-octadecenoic and 12(13)-epoxy-9Z-octadecenoic acid (EpOMEs) as well as 12,13-dihydroxy-9Z-octadecenoic acid (DiHOME) were increased in VC of children from mothers with an anthroposophic lifestyle. Accordingly, VC was found to be rich in multiple classes of bioactive lipid mediators, which evidence lifestyle, gender and gestational week dependencies. Levels of lipid mediators in VC may therefore be useful as early stage non-invasive markers of the development of the skin as a protective barrier.

Figure 1. Levels of sphingolipid, oxylipin and endocannabinoid species in vernix caseosa (VC) affected by gestational period, gender of the child or lifestyle of the mother.

See Supplementary Table S1 for compound nomenclature. P-values for the linear regression of one of the factors adjusted for the other two as covariates are displayed. All indicated changes were corrected for multiple hypothesis testing using the Storey q-value.

Figure 2. The ceramide to sphingomyelin ratio increased with gestational period.

(a) General structure for ceramides and sphingomyelins belonging to the non hydroxylated fatty acid/sphingosine backbone (NS) sphingolipid class. (R1 = fatty acid alkyl chain; R2 = (CH₂)₁₂CH₃)). (b–g) levels for specific R1 chain lengths according to the gestational period. Early term = 36–38 weeks, Full term = 39–40 weeks and post term = 41–42 weeks. Bonferroni corrected p-values corresponding to the linear regression of gestational period adjusted for lifestyle of the mother and gender of the baby are presented. Each point represents an individual. The arithmetic mean with 95% confidence intervals is presented.

Figure 3. Structures and phenotypic differences in levels of (a) 12(13)-epoxy-9Z-octadecenoic acid (12[13]-EpOME) and (b) 12,13-dihydroxy-9Z-octadecenoic acid (12,13-DiHOME) according to lifestyle (A = anthroposophic; P = partly anthroposophic; NA = non- anthroposophic).

The 12(13)-EpOME is converted to the 12,13-DiHOME via activity of the enzyme soluble epoxide hydrolase (sEH). Bonferroni corrected p-values corresponding to the linear regression of lifestyle of the mother adjusted for gestational period and gender of the baby are presented. Each point represents an individual. The arithmetic mean with 95% confidence intervals is presented.