Abstract
Complex mixtures of persistent organic pollutants (POPs) are regularly detected in the environment and animal tissues. Often these chemicals are associated with latent effects following early-life exposures, following the developmental origin of health and disease paradigm. We investigated the long-term effects of a human relevant mixture of 29 POPs on adult zebrafish following a developmental exposure, in addition to a single PFOS exposure for comparison, as it was the compound with the highest concentration within the mixture. Zebrafish embryos were exposed from 6 to 96h post fertilization to x10 and x70 the level of POP mixture or PFOS (0.55 and 3.83μM) found in human blood before being transferred to clean water. We measured growth, swimming performance, and reproductive output at different life stages. In addition, we assessed anxiety behavior of the adults and their offspring, as well as performing a transcriptomic analysis on the adult zebrafish brain, as the POP mixture and PFOS concentrations used are known to affect larval behavior. Exposure to POP mixture and PFOS reduced swimming performance and increased length and weight, compared to controls. No effect of developmental exposure was observed on reproductive output or anxiety behavior. Additionally, RNA-seq did not reveal pathways related to anxiety although pathways related to synapse biology were affected at the x10 PFOS level. Furthermore, pathway analysis of the brain transcriptome of adults exposed as larvae to the low concentration of PFOS revealed enrichment in pathways such as calcium, MAPK, and GABA signaling, all of which are important for learning and memory. Based on our results we can conclude that some effects on the endpoints measured were apparent, but if these effects lead to adversities at population levels remains elusive.
Highlights
Persistent organic pollutants (POPs) are omnipresent in the envi ronment leading to humans and wildlife experiencing a near continuous exposure to these chemicals (WHO/UNEP 2012)
A single PFOS exposure was chosen for comparison due to it being the most abundant constituent of the POP mixture and we have previously found it is responsible for behavioral effects seen in larvae exposed to our POP mixture (Khezri et al, 2017)
A similar increase in body mass was recorded in 5 mo zebrafish exposed to a mixture of POPs through feeding accompanied with changes in path ways involved in endocrine signaling and weight homeostasis (Nour izadeh-Lillabadi et al, 2009; Lyche et al, 2011)
Summary
Persistent organic pollutants (POPs) are omnipresent in the envi ronment leading to humans and wildlife experiencing a near continuous exposure to these chemicals (WHO/UNEP 2012). Many POPs are endocrine disrupting chemicals (EDCs) defined as “an exogenous substance or mixture that alters function(s) of the endocrine system and causes adverse health effects in an intact or ganism, or its progeny, or (sub) populations” (EC 2019). Since hormone balance is of particular importance during early development, early-life exposure to EDCs are expected to increase the susceptibility to disease in later-life, following the developmental origins of health and disease (DOHaD) hypothesis (Hanson and Gluckman 2014). Early-life exposure to EDCs are associated with later-life effects on cardiovascu lar, metabolic, and reproductive function, as well as being associated with the development of obesity, diabetes, and cancer in humans and experimental models (Zhang and Ho 2011; Barouki et al, 2012). Exposure of pregnant female rats to a PCB mixture led to increased body weight and lineage-specific effects of exposure were found for serum progesterone and estradiol in the F2 and F3 generations that were not observed in the directly exposed F1 offspring (Mennigen et al, 2018)
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