Associations of Perfluoroalkyl Substances with Adipocytokines in Umbilical Cord Serum: A Mixtures Approach

Abstract

BackgroundPer- and polyfluoroalkyl substances (PFAS), a kind of emerging environmental endocrine disruptors, may interfere with the secretion of adipokines and affect fetal metabolic function and intrauterine development. However, the epidemiological evidence is limited and inconsistent. We examined the associations of single and multiple PFAS exposures in utero with adipocytokine concentrations in umbilical cord serum.MethodsA total of 1111 mother-infant pairs from Sheyang Mini Birth Cohort Study (SMBCS) were included in this study. We quantified 12 PFAS and two adipokine, namely leptin and adiponectin, in umbilical cord serum. Generalized linear models and Bayesian Kernel Machine Regression (BKMR) models were applied to estimate the associations of single- and mixed- PFAS exposure with adipokines, respectively. Interaction terms between PFAS exposure and infant gender were included in each model to assess the sexually dimorphic effects of PFAS.Results10 PFAS in cord serum were detected with a median concentration (μg/L) ranging from 0.04 to 3.97, [expect for PFOSA (detection rates 2.7%) and PFDS (detection rate 1.7%), which were not evaluated in this study]. In generalized linear models, significant negative associations with leptin [regression coefficient, (β): -0.429 ~ -0.221, P <0.05] and positive associations with adiponectin (β: 0.059 ~ 0.168, P <0.05) were observed for most single PFAS concentrations in cord serum. Similar associations of PFAS mixtures with adipokines were found in the BKMR model. Meanwhile, PFHpA, PFOS, PFNA, PFHpS, and PFBS were identified as important contributors. Gender differences of associations between PFAS and adiponectin were observed in both generalized linear models and BKMR models.ConclusionsPFAS levels were significantly associated with adipokines in cord serum, suggesting that intrauterine mixture of PFAS exposure may be related to decreased fetal leptin level but increased fetal adiponectin level, and the associations appeared to be sex-specific.

Keywords: PFAS, adipokine, mixtures, BKMR models, cord serum