Transcriptomic alterations in the brain of painted turtles (Chrysemys picta) developmentally exposed to bisphenol A or ethinyl estradiol

Abstract

Developmental exposure of turtles and other reptiles to endocrine-disrupting chemicals (EDCs), including bisphenol A (BPA) and ethinyl estradiol (EE), can stimulate partial to full gonadal sex-reversal in males. We have also recently shown that in ovo exposure to either EDC can induce similar sex-dependent behavioral changes typified by improved spatial learning and memory or possibly feminized brain responses. Observed behavioral changes are presumed to be due to BPA- and EE-induced brain transcriptomic alterations during development. To test this hypothesis, we treated painted turtles () at developmental , incubated at 26°C (male-inducing temperature), with) BPA (1 ng/µl), ) EE (4 ng/µl), or) vehicle ethanol (control group). Ten months after hatching and completion of the behavioral tests, juvenile turtles were euthanized, brains were collected and frozen in liquid nitrogen, and RNA was isolated for RNA-Seq analysis. Turtles exposed to BPA clustered separately from EE-exposed and control individuals. More transcripts and gene pathways were altered in BPA vs. EE individuals. The one transcript upregulated in both BPA- and EE-exposed individuals was the mitochondrial-associated gene, ND5, which is involved in oxidative phosphorylation. Early exposure of turtles to BPA increases transcripts linked with ribosomal and mitochondrial functions, especially bioenergetics, which has been previously linked with improved cognitive performance. In summary, even though both BPA and EE resulted in similar behavioral alterations, they diverge in the pattern of neural transcript alterations with early BPA significantly upregulating several genes involved in oxidative phosphorylation, mitochondrial activity, and ribosomal function, which could enhance cognitive performance.

Impacts of bisphenol A analogues on zebrafish post‐embryonic brain

“…The detailed analysis of the hypothalamic regions in post‐embryonic developmental stages did not provide evidence for disruption in the numbers of mitotically active progenitors and neurones and it is likely that other brain regions might be affected at cellular levels in the bisphenol‐treated larval zebrafish. Indeed, other studies have shown BPA effects on brain regions others than hypothalamus 128,129 . Thus, further analysis should be performed in multiple brain regions to assess how bisphenols affect the neurobehavioural system.…”

Gene expression and DNA methylation changes in the hypothalamus and hippocampus of adult rats developmentally exposed to bisphenol A or ethinyl estradiol: a CLARITY-BPA consortium study

“…This finding may suggest that exposure to one of these EDCs disrupts the normal neural pathways that regulate select behaviors. We previously determined that developmental exposure to BPA or EE in painted turtles resulted in significant gene expression changes, especially those associated with mitochondrial and ribosomal protein functions, that correlated with prior performance when tested in an aquatic spatial maze [72]. While such analyses cannot establish causation, they suggested a list of candidate genes that may be vulnerable to early life exposure to BPA or EE and contribute to behavioral changes later-inlife.…”

The Growth Behavior of Chlorella vulgaris in Bisphenol a under different Cultural Conditions

“…Bisphenol A (BPA), which is made by Phenol and acetone [2], is an industrially important chemical that is used as a raw material in the manufacture of many products such as engineering plastics (e.g., epoxy resins/ polycarbonate plastics), food cans (i.e., lacquer coatings), and dental composites/sealants [3]. Extensive evidence indicates that BPA induces feminization during gonadal ontogeny of fishes [4], reptiles [5], birds [6], and human [7,8], and it is identified as an endocrine disruptor and leads to carcinogenesis [9]. Biology is exposed to ubiquitous BPA Though its hazardous effects, more than 5 million metric tons of BPA was produced in 2011 and was mainly used in East Asia (Korea, China and Japan), and kept increasing year by year [10,11].…”