EFFECT OF ENDOCRINE DISRUPTING MIXTURES AND CHEMICALS ON THE OXYGEN CONSUMPTION RATE OF ZEBRAFISH LARVAE

Abstract

Chemicals affecting the endocrine system, so called endocrine disrupting chemicals (EDC’s), have been steadily increasing in the environment over the last 40 years. EDCs are harmful chemicals since they can act through multiple endocrine pathways, contain a wide spectrum of health effects that can be very persistent and can cause effects already at a low doses. Furthermore, these chemicals enter the environment through several routes and are used in multiple common consumer products. Besides that, we are not exposed to one of them at a time but to various mixtures of EDC’s simultaneously.

The Swedish Environmental Longitudinal Mother and child Asthma and allergy (SELMA) pregnancy cohort study identified a mixture of 20 EDC’s and metabolites in blood and urine samples of women approximately 10 weeks pregnant. Using the ratios of concentration of the EDC’s found in the women, mixtures of EDC’s were designed. Among them is the growth mixture (mix G) that was associated with low birth weight. Mixture G contains chemicals such as phthalates, phenols and perfluorinated chemicals, which are known environmental contaminants.

Previous studies revealed that mix G can influence birth weight through dysregulating the expression of key genes involved in thyroid hormone (TH) signalling and thus by disrupting the thyroid axis. Environmental contaminants causing mutations or dysregulations in these genes can lead to IQ loss and modified brain structure in offspring, slow growth, insulin resistance and lipid accumulation.

Previous studies have focused on the gene networks important for TH signalling and hence neurological effects. The presented study extends on that knowledge focusing on what the impact is of the EDC’s in mix G on energy metabolism and how it is related to the low birth weight. This was achieved by studying the impact of mix G on metabolic rate, which is influenced by TH signalling. The standard metabolic rate can be measured as oxygen consumption in a resting state. Oxygen consumption is influenced by oxidative energy metabolism in the mitochondria, which TH can affect via nuclear pathways or non-nuclear pathways. Oxygen consumption was measured with a respirometry protocol optimized for zebrafish larvae. Zebrafish larvae are exposed to mix G and its individual chemicals (PFOA, PFOS, MEHP and Triclosan) for 48h after which their oxygen consumption was measured using a respirometry microplate system (Loligo® Systems). Even though the results do not show a significant difference with the control, the results suggest that mix G and its individual chemicals can affect the oxygen consumption rate. Pilot experiments were also performed on three week old zebrafish larvae, which show some interesting results.