Effects of an environmentally relevant phthalate mixture on anxiety-like behavior, circadian activity, and neural gene expression

Toxicity studies have shown that exposure to endocrine-disrupting chemicals (EDCs) has adverse effects on the health of humans and animals, affecting reproductive, behavioral, and neural systems. Exposure to phthalates, during development or in adulthood, leads to reproductive, behavioral, and cognitive deficits in animal studies. Phthalates are plasticizers that are known EDCs. Phthalate metabolites have been detected in 96% of 2,685 individuals. However, it's unknown how developmental treatment with an environmentally relevant phthalate mixture impacts anxiety-like behavior, circadian rhythm, and how adult exposure impacts the medial preoptic area (mPOA) of the hypothalamus, a conserved region that is hormone-sensitive and regulates locomotor activity in animals. Phthalates act on steroid receptors such as androgen and estrogen receptors, and nuclear receptors such as peroxisome proliferator-activated receptors. I have three aims for this thesis. First, I examined the effects of prenatal exposure to an environmentally relevant phthalate mixture on anxiety-like behavior in adult male and female mice (Chapter 3). Second, I examined the impact of the mixture on adult male and female mice circadian activity rhythms (Chapter 4). Finally, the hormone-sensitive mPOA is implicated in locomotor rhythms and is speculated to be involved in anxiety. In Chapter 5, I examined the impact of daily adult exposure to the mixture on the transcriptome of the female mPOA. Mechanisms of neurodevelopmental toxicity include altering neurotransmitter systems, intracellular signaling, and oxidative stress, amongst others. Although we did not interrogate these directly, the last chapter provides potential signaling pathways for future investigation. Presented here, developmental exposure to the phthalate mixture affects anxiety-like behavior subtly. I found a significant effect of developmental exposure to the mixture on the number of transitions in the light-dark box test in both male and female mice. Secondly, the phthalate mixture affected the circadian rhythms of male mice. The circadian rhythms of female mice were unaffected. In the last chapter, the transcriptome of the female mPOA was primarily affected through downregulation. These data reveal the effects of exposure to a phthalate mixture on anxiety-like behavior and circadian rhythms. I also propose the glutamatergic signaling pathway as a novel pathway for EDC exposure. Future work should aim to establish EDCs as neuroendocrine disruptors because EDCs have been shown to affect the neuroendocrine system.

Name thesis:degree_name

Ph.D.

Level thesis:degree_level

Dissertation

Discipline thesis:degree_discipline

Neuroscience

Grantor

University of Illinois at Urbana-Champaign

Year dc:date

2022

Author dc:creator

• Soriano, Stephanie

Contributors dc:contributor

• Mahoney, Megan
• Raetzman, Lori
• Flaws, Jodi
• Christian-Hinman, Catherine

• Neuroscience
• Toxicology

Statement dc:rights

• Copyright 2022 Stephanie Soriano

Language dc:language

en, eng

Handle dc:identifier

https://hdl.handle.net/2142/115584

OAI record oai:identifier

https://www.ideals.illinois.edu/oai-pmh?verb=GetRecord&metadataPrefix=etdms&identifier=oai%3Awww.ideals.illinois.edu%3A2142%2F115584