Sexually dimorphic transcriptomic responses in the teleostean hypothalamus: A case study with the organochlorine pesticide dieldrin

Abstract

Organochlorine pesticides (OCPs) such as dieldrin are a persistent class of aquatic pollutants that cause adverse neurological and reproductive effects in vertebrates. In this study, female and male largemouth bass (Micropterus salmoides) (LMB) were exposed to 3 mg dieldrin/kg feed in a 2 month feeding exposure (August–October) to (1) determine if the hypothalamic transcript responses to dieldrin were conserved between the sexes; (2) characterize cell signaling cascades underlying dieldrin neurotoxicity; and (3) determine whether or not co-feeding with 17β-estradiol (E2), a hormone with neuroprotective roles, mitigates responses in males to dieldrin. Despite also being a weak estrogen, dieldrin treatments did not elicit changes in reproductive endpoints (e.g. gonadosomatic index, vitellogenin, or plasma E2). Sub-network (SNEA) and gene set enrichment analysis (GSEA) revealed that neuro-hormone networks, neurotransmitter and nuclear receptor signaling, and the activin signaling network were altered by dieldrin exposure. Most striking was that the majority of cell pathways identified by the gene set enrichment were significantly increased in females while the majority of cell pathways were significantly decreased in males fed dieldrin. These data suggest that (1) there are sexually dimorphic responses in the teleost hypothalamus; (2) neurotransmitter systems are a target of dieldrin at the transcriptomics level; and (3) males co-fed dieldrin and E2 had the fewest numbers of genes and cell pathways altered in the hypothalamus, suggesting that E2 may mitigate the effects of dieldrin in the central nervous system.

Current concepts in neuroendocrine disruption

“…Organochlorine pesticides are considered legacy pesticides, having been restricted or banned in use in the past three to four decades (e.g., methoxychlor, dieldrin); however there remain significant environmental exposure risks because OCPs are highly persistent in the environment and bioaccumulate in tissues (Gallagher et al, 2001; Martyniuk et al, 2013). One criterion to be considered for a chemical being classified as a direct-acting neuroendocrine disruptor is that the parent compound must cross the blood-brain barrier in order to exert central neuroendocrine effects.…”

“…Male and female bass were fed 3 mg dieldrin/kg food over 2 months (Martyniuk et al, 2013). This concentration was selected to mirror environmental exposures that occur in contaminated sites, specifically the Superfund site of Lake Apopka in Central Florida.…”

“…Transcriptomic analysis revealed that neuroendocrine and neurotransmitter signaling were differentially affected in a sex-specific manner in the hypothalamus. Gene network analysis revealed that transcripts associated with activin signaling pathways were significantly reduced 20–30% by dieldrin in males (Martyniuk et al, 2013). Moreover, based upon the bioinformatics approach used, activin signaling was also associated with GnRH, growth hormone 1, and insulin-like growth factor 1 receptor signaling (Martyniuk et al, 2013), suggesting that dieldrin affects multiple neurohormonal systems at the transcript level.…”

Transcriptomic profiling in Silurana tropicalis testes exposed to finasteride

“…SNEA uses known relationships (i.e., based on expression, binding, and common pathways) between genes to build networks focused around gene hubs. This approach has been applied in biomarker discovery in mammals (Kotelnikova et al, 2012) and for gene and protein networks in teleost fishes (Martyniuk et al, 2012;Martyniuk et al, 2013a). Additional details can be found in the technical bulletin page 717 from Pathway Studios 7.0 as well as in Chishti et al (2013).…”

Brain quantitative proteomic responses reveal new insight of benzotriazole neurotoxicity in female Chinese rare minnow (Gobiocypris rarus)

“…Previous studies have shown that pollutants are capable of disrupting the neuroendocrine system of teleost fish, and many chemicals found in the environment can include neurotoxic mode of action (Martyniuk et al, 2013;Richter et al, 2014). These adverse responses in fish can include the modulation of the brain proteome.…”