Prenatal and Neonatal Exposure to Perfluorooctane Sulfonic Acid Results in Changes in miRNA Expression Profiles and Synapse Associated Proteins in Developing Rat Brains

Abstract

We previously identified a number of perfluorooctane sulfonic acid (PFOS)-responsive transcripts in developing rat brains using microarray analysis. However, the underlying mechanisms and functional consequences remain unclear. We hypothesized that microRNAs (miRNAs), which have emerged as powerful negative regulators of mRNA and protein levels, might be responsible for PFOS-induced mRNA changes and consequent neural dysfunctions. We used eight miRNA arrays to profile the expression of brain miRNAs in neonatal rats on postnatal days (PND) 1 and 7 with maternal treatment of 0 (Control) and 3.2 mg/kg of PFOS feed from gestational day 1 to PND 7, and subsequently examined six potentially altered synapse-associated proteins to evaluate presumptive PFOS-responsive functions. Twenty-four brain miRNAs on PND 1 and 17 on PND 7 were significantly altered with PFOS exposure (P < 0.05), with miR-466b, -672, and -297, which are critical in neurodevelopment and synapse transmission, showing a more than 5-fold reduction. Levels of three synapse-involved proteins, NGFR, TrkC, and VGLUT2, were significantly decreased with no protein up-regulated on PND 1 or 7. Perfluorooctane sulfonic acid might affect calcium actions during synapse transmission in the nervous system by interfering with SYNJ1, ITPR1, and CALM1 via their targeting miRNAs. Our results indicated that miRNA had little direct regulatory effect on the expression of mRNAs and synapse-associated proteins tested in the developing rat brain exposed to PFOS, and it seems that the PFOS-induced synaptic dysfunctions and changes in transcripts resulted from a combinatory action of biological controllers and processes, rather than directed by one single factor.