About

Andrea C. Gore, Ph.D., is a Professor of Pharmacology & Toxicology and holds the Vacek Chair in Pharmacology at the University of Texas at Austin. Her work in the Gore Laboratory focuses on the effects of endocrine-disrupting chemicals (EDCs) on the neuroendocrine control of reproduction and behavior. Her current research involves using a rat model to understand how prenatal exposure to environmental endocrine disruptors alters the developing brain by inducing molecular and cellular changes in neurons within the hypothalamus and other brain regions. Beyond investigating the direct effects of EDCs on developing individuals, her research also explores how EDC exposures can lead to multigenerational behavioral changes through epigenetic actions on the germline and gametes, which are the precursors to ova and sperm, thereby affecting subsequent generations. Her team employs a variety of techniques, including behavioral, physiological, neuroanatomical, immunohistochemical, and molecular approaches such as gene expression, transcriptomics, epigenetic profiling, DNA methylation, RNAscope, and hormone assays.

Research topics

• Endocrinology
• Biology
• Medicine
• Internal medicine
• Neuroscience
• Intensive care medicine
• Psychology
• Bioinformatics
• Genetics

Selected publications

• Transcriptomic analysis of effects of developmental PCB exposure in the hypothalamus of female rats

  Molecular and Cellular Endocrinology · 2025-01-09 · 5 citations

  articleOpen accessSenior authorCorresponding

  This study investigated the consequences of perinatal exposure to Aroclor 1221 (A1221), a weakly estrogenic polychlorinated biphenyl (PCB) mixture and known endocrine-disrupting chemical (EDC), in female rats. Previous work has shown behavioral and physiological effects of A1221, and the current study extended this work to comprehensive transcriptomic profiling of two hypothalamic regions involved in the control of reproduction: the arcuate nucleus (ARC) and anteroventral periventricular nucleus (AVPV). Female Sprague-Dawley rats were fed a cookie treated with a small volume of A1221 (1 mg/kg) or vehicle (3% DMSO in sesame oil) during pregnancy from gestational days 8-18 and after birth from postnatal (P) days 1-21, exposing the offspring via placental and lactational transfer. In female offspring, developmental, physiological, and hormonal effects of A1221 were relatively modest. However, because prior work has implicated this exposure in neurobehavioral disruptions, we sought to determine whether developmental programming of the brain transcriptome could underlie these latter phenotypes. We used 3' targeted RNA sequencing in the hypothalamus (arcuate nucleus, anteroventral periventricular nucleus) of experimental females at P8, 30, and 60 and identified significant alterations in gene expression and gene ontology (GO) terms in an age- and tissue-specific manner. Most notably, terms related to synaptic signaling, neurotransmitter regulation, immune response, and cellular structure were identified. Changes in pathways associated with synaptic functions and cellular metabolism were further identified, indicating that A1221 exposure can impact neurodevelopmental and neuroendocrine processes at a molecular level, even in the absence of overt developmental changes. These findings of molecular reprogramming may explain the behavioral effects of A1221 and highlight novel molecular targets and pathways that warrant further investigation to understand the effects of EDCs on the developing brain.

  PublisherDOI

• Cognitive effects of early life exposure to PCBs in rats: Sex-specific behavioral, hormonal and neuromolecular mechanisms involving the brain dopamine system

  Hormones and Behavior · 2025-02-08 · 6 citations

  articleOpen accessSenior authorCorresponding

  Endocrine-disrupting chemicals (EDCs) are environmental toxicants that disrupt hormonal and neurodevelopmental processes. Among these chemicals, polychlorinated biphenyls (PCBs) are particularly concerning due to their resistance to biodegradation and tendency to bioaccumulate. PCBs affect neurodevelopmental function and disrupt the brain's dopamine (DA) system, which is crucial for attentional, affective, and reward processing. These disruptions may contribute to the rising prevalence of DA-mediated neuropsychiatric disorders such as ADHD, depression, and substance use disorders. Notably, these behaviors are sexually dimorphic in part due to differences in sex hormones and their receptors, which are targets of estrogenic PCBs. Therefore, this study determined effects of early life PCB exposure on behaviors and neurochemistry related to potential disruption of dopaminergic signaling. Male and female Sprague Dawley rats were exposed to the PCB mixture Aroclor 1221 (A1221) or vehicle perinatally and then underwent a series of behavioral tests in adulthood, including the sucrose preference test to measure anhedonia, conditioned orienting to assess incentive-motivational phenotype, and attentional set-shifting to evaluate cognitive flexibility and response latency. Following these tests, rats were euthanized, and serum estradiol (E2), DA cells in the midbrain ventral tegmental area (VTA) and substantia nigra (SN), and gene expression from those combined midbrain nuclei were measured. Female rats exposed perinatally to A1221 exhibited decreased sucrose preference, and both male and female A1221 rats had reduced response latency in the attentional set-shifting task compared to vehicle counterparts. Conditioned orienting and serum estradiol (E2)were not affected in either sex; however, A1221-exposed rats of both sexes displayed higher TH+ cell numbers in the VTA and increased expression of dopamine receptor 1 (Drd1) in the combined midbrain nuclei. Additionally, E2 uniquely predicted behavioral outcomes and VTA DAergic cell numbers in A1221-exposed female rats, whereas DA signaling genes were predictive of behavioral outcomes in males. These data highlight sex-specific effects of A1221 on neuromolecular and behavioral phenotypes.

  PublisherDOI

• Sex- and Lineage-Dependent Transgenerational Effects of Vinclozolin and Flutamide on Rat Development and Behavior

  Journal of the Endocrine Society · 2025-11-05

  articleOpen accessSenior author

  Vinclozolin (VIN) is an agricultural fungicide that acts as an endocrine-disrupting chemical (EDC), primarily through its anti-androgenic actions. Developmental exposure to VIN is linked with reproductive and neurodevelopmental alterations; furthermore, VIN was the first EDC identified as causing heritable epigenetic transmission across generations. The present study provides a more detailed and comprehensive look into the developmental and transgenerational behavioral effects of VIN exposure in rats, with the experiment designed to investigate the influence of sex differences and parental lineage (maternal, paternal). Specifically, dams were exposed to either the vehicle (DMSO; negative control), VIN (100 mg/kg), or flutamide (FLUT; 1 mg/kg), the latter an anti-androgenic compound used as a positive control for the anti-androgenic effects of VIN. Developmental measures, anxiety, and social tests were conducted on males and females from the F1 (direct prenatal exposure) and F3 (ancestral exposure through epigenetic inheritance) generations. Generally, effects were sexually dimorphic, lineage-specific, and differed between FLUT and VIN, pointing to different mechanisms of the chemicals. More behavioral effects of VIN emerged at the F3 generation's paternal lineage compared to the F1 generation. Overall, this study provides more detailed insight into the transgenerational effects of a high dose of VIN exposure and suggests future inquiry into the mechanisms of action of the EDC, specifically as it pertains to its differences from FLUT and its differing effects on lineage, sex, and generation.

  PublisherOA PDFDOI

• Sex differences in microglia morphology and function across the lifespan are mediated by the early hormone environment

  Brain Behavior and Immunity · 2025-11-20 · 3 citations

  articleOpen access
  PublisherOA PDFDOI

• Transcriptomic Changes Across the HPG Axis Following Prenatal Exposure to the EDC Mixture NeuroMix

  Endocrinology · 2025-08-25 · 3 citations

  articleOpen accessSenior author

  Endocrine-disrupting chemicals (EDCs) are exogenous chemicals that are ubiquitous in our environment and found in everyday items. We previously reported that prenatal exposure of rats to a human-relevant mixture of EDCs, NeuroMix (NMX), led to alterations in physiological and behavioral phenotypes. Here, we used hypothalamic-pituitary-gonadal (HPG) tissues from these same male and female rats and conducted 3' Tag-based RNA sequencing (TagSeq) to investigate underlying molecular mechanisms. TagSeq revealed unique tissue- and sex-specific differentially expressed genes (DEGs). In males, among the HPG tissues, NMX had the greatest effects in the hypothalamic arcuate nucleus (ARC), with 613 DEGs. Gene ontology (GO) enrichment analysis revealed that genes upregulated in the ARC of NMX males were involved in synaptic plasticity, while genes downregulated related to responses to estradiol and glucocorticoids. In females, prenatal NMX exposure induced the largest transcriptome change in the ovaries, with 1295 DEGs. GO-enrichment analysis revealed upregulation of genes involved in cilium organization and movement, while genes downregulated in this region were related to immune-related processes. Using Qiagen Ingenuity Pathway Analysis, we identified the β-estradiol pathway to be activated in all NMX female tissues and the NMX male pituitary, and inhibited in NMX male ARC, ventromedial nucleus, and testes. To our knowledge, this is one of the first studies to conduct transcriptomic profiling across HPG tissues, with these results demonstrating that prenatal exposure to NMX affects gene expression across the HPG axis in a sex-dependent manner.

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• SAT-244 Effects of endocrine-disrupting chemicals on behavioral and transcriptomic properties during sexual differentiation of the brain in rats

  Journal of the Endocrine Society · 2025-10-01

  articleOpen access

  Abstract Disclosure: S.E. Khoury: None. E. Morales-Grahl: None. L. Thompson: None. A.C. Gore: None. N.Y. Eldiraoui: None. This study aims to evaluate how early life exposure of rats to endocrine-disrupting chemicals (EDCs) affects development and sexual differentiation of the brain through molecular and epigenetic programming. Our lab and others have shown that EDC exposure affects the hypothalamus in a sex, time, and exposure dependent manner. These effects lead to changes in gene expression related to gonadal steroid hormone signaling in the brain, shifts in pubertal timing, and altered DNA methylation patterns in hypothalamic regions. Current work is addressing effects of EDC exposure on mating behaviors in rats and whether epigenetic modification in brain regions involved in these behaviors underlie any observed physiological changes. In our lab we use NeuroMix, an EDC mixture containing 9 common industrial chemicals at environmentally relevant doses. We expose rats orally to NeuroMix in early postnatal life through feeding of rat dams, during hormone sensitive periods of brain development in the offspring. Brain tissues are collected at postnatal day 1, adolescence, and during early adulthood and bed nucleus of the stria terminalis and preoptic area of the hypothalamus are dissected for Tag-Seq to look at mRNA expression and whole genome bisulfite sequence (WGBS) to assess changes to gene expression and DNA methylation associated with sex differences at these time points. In adulthood, a subset of early adult males are observed in a natural mating environment and number of and latency to mounts, intromission, and ejaculation are counted. A subset of early adult females are tested and recorded in a paced mating paradigm to uncover differences in female typical sexual behaviors due to NeuroMix treatment. The results of these experiments will provide novel insights into the effects of NeuroMix treatment on sexually dimorphic behaviors and brain epigenetics. Supported by NIH R35 ES035024 Presentation: Saturday, July 12, 2025

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• SAT-027 Transcriptomic Profiles of the HPG Axis in Males and Females After Prenatal Exposure to the EDC Mixture NeuroMix

  Journal of the Endocrine Society · 2025-10-01

  articleOpen accessSenior author

  Abstract Disclosure: T.M. Milewski: None. M. Streifer: None. L. Thompson: None. D. Sheinhaus: None. A. Hayes: None. A.C. Gore: None. Endocrine-disrupting chemicals (EDCs) are exogenous chemicals ubiquitous in our environment and found in everyday items. Most mammals, including humans, are exposed to changing mixtures of EDCs throughout their lives depending upon environmental factors, including geography, diet, lifestyle, and socioeconomic status. Previous work has revealed that several EDCs alter reproductive physiology and behavior and change gene expression to control reproduction. This study used a rat model to investigate transcriptome changes via 3’ tag-based RNA sequencing (Tagseq) in response to prenatal exposure to a low-dose mixture of environmentally relevant EDCs named NeuroMix (NMX) across the hypothalamic-pituitary-gonadal (HPG) axis. RNA was extracted from the hypothalamic arcuate nucleus (ARC) and ventromedial nucleus (VMN), the anterior pituitary, and the gonads of male and female rats that had been exposed to NMX or control treatments to identify potential gene and pathway targets affected by EDC exposure. Among tissues most affected by treatment were the ARC of males, with 613 differentially expressed genes (DEGs). GO-enrichment analysis revealed genes up-regulated in the ARC of NMX males were involved in synaptic plasticity, while genes down-regulated related to responses to estradiol and glucocorticoids. In females, prenatal NMX exposure showed the largest transcriptome change in the ovaries, with 1295 DEGs. GO-enrichment analysis revealed up-regulation of genes involved in cilium organization and movement, while genes down-regulated in this region were related to immune-related processes. Relatively few DEGs were identified in the testes. Using Qiagen Ingenuity Pathway Analysis, we identified the beta-estradiol pathway to be activated in all NMX female tissues and NMX male pituitary, and inhibited in NMX male, ARC, VMN, and testes. Overall, these results demonstrate that prenatal exposure to NMX affects gene expression across the HPG axis in a sex dependent matter. Presentation: Saturday, July 12, 2025

  PublisherOA PDFDOI

• Transcriptomic profiling of hypothalamic development in female rats

  Molecular and Cellular Endocrinology · 2025-07-19

  articleOpen accessSenior authorCorresponding

  The hypothalamic arcuate nucleus (ARC) and anteroventral periventricular nucleus (AVPV) are critical regulators of reproductive function, energy balance, stress, and neuromodulation. These regions undergo substantial changes in neural and glial populations over development that enable the acquisition of adult functions. Although previous studies have examined developmental changes in specific hypothalamic cell populations or gene families, to our knowledge, none has comprehensively compared unbiased/bulk transcriptional profiles across key developmental stages in both the ARC and AVPV. In this study, we used 3′ targeted RNA sequencing to profile gene expression in the ARC and AVPV of female rats at infantile (P8), peripubertal (P30), and adult (P60) life stages. We conducted unbiased and a priori selected differential gene expression analyses, the latter genes selected for their roles in reproduction, metabolism, stress, and neuromodulation. We also measured serum hormones as an index of physiology. Developmental analyses revealed robust differential gene expression between the infantile and prepubertal periods in both the ARC and AVPV, with substantial transcriptional overlap between regions. Fewer and more region-specific transcriptional changes were observed during the transition to adulthood. Gene ontology (GO) analyses revealed coordinated developmental programming prior to puberty, including downregulation of developmental processes and upregulation of metabolic and regulatory pathways. In adulthood, the AVPV showed continued transcriptional remodeling, while the ARC remained comparatively stable. FSH emerged as the strongest hormonal correlate of a priori hypothalamic gene expression. These data provide a reference for understanding hypothalamic development and hormone–gene interactions across life stages in the female rat. • Hypothalamic ARC and AVPV transcriptomic profiles were compared across development. • Robust DEG expression occurred when comparing the peripubertal to neonatal periods. • Peripuberty was linked to reduced developmental and increased metabolic processes. • The AVPV continued remodeling into adulthood while the ARC remained stable. • FSH was the strongest hormonal correlate of hypothalamic gene expression.

  PublisherDOI

• SAT-460 Do Endocrine-Disrupting Chemicals Cause Heritable Changes in Reproduction?

  Journal of the Endocrine Society · 2024-10-01

  articleOpen accessSenior author

  Abstract D.L. Sheinhaus: None. Successful reproduction depends upon a precise homeostasis involving hormones and their actions on the reproductive tract. These processes can be perturbed by environmental toxicants such as endocrine-disrupting chemicals (EDCs), which are associated with reproductive diseases. EDCs are ubiquitous environmental toxicants present in food and beverages, pesticides, medical tubing, and personal care products, among other sources. Early life development (fetus and infant) are amongst the most susceptible populations to EDCs, as disrupting hormones during these hormonally sensitive periods can significantly affect the developmental origins of health and disease. This project focuses on how EDC exposures during development cause epigenetic molecular programming of the reproductive tract in males, setting the stage for reproductive abnormalities. Work is conducted on the epididymis, where sperm travel from caput to cauda and undergo final stages of maturation. Part of the maturation process includes interaction with their surrounding environment, including extracellular vesicles (EVs). EVs of the epididymis, named epididymosomes, bud off of cellular membranes and are released into epididymal fluid. Epididymosomes transmit signals that play an important role in sperm development via molecular cargo that can be transmitted to sperm, causing changes to the latter’s gene expression and function, and affect reproductive outcomes. Our experiment uses a rat model to investigate how EDCs reprogram epididymal EV molecular contents. Rats are bred and pregnant dams are fed with a mixture of common EDCs. This exposes not only the dam but also her fetuses (F1 generation) and within the fetuses, the cells that will eventually become sperm or ova and (F2 generation). Male offspring are monitored for development and in adulthood, they are euthanized to collect and isolate epididymal EVs and sperm for subsequent RNA sequencing. I hypothesize that exposure to EDCs during development impairs male reproductive capacity through epigenetic programming, subsequently perturbing sperm maturation. Future work will determine how EDCs influence RNA and DNA of sperm in the epididymis. Saturday, June 1, 2024

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• Two Hits of EDCs Three Generations Apart: Evaluating Multigenerational Anxiety-Like Behavioral Phenotypes in Female Rats Exposed to Aroclor 1221 and Vinclozolin

  Environmental Health Perspectives · 2024-12-01 · 3 citations

  articleOpen accessSenior author

  BACKGROUND: Endocrine-disrupting chemicals (EDCs) are exogenous chemical compounds that interfere with the normal function of the endocrine system and are linked to direct and inherited adverse effects in both humans and wildlife. Legacy EDCs such as polychlorinated biphenyls (PCBs) are no longer used yet remain detectable in biological specimens around the world; concurrently, we are exposed to newer EDCs like the fungicide vinclozolin (VIN). This combination of individuals' direct environmental chemical exposures and any heritable changes caused by their ancestors' chemical exposures leads to a layered pattern of both direct and ancestrally inherited exposures that might have cumulative effects over generations. OBJECTIVES: We assessed consequences of both direct and ancestral exposure to EDCs over six generations, examining anxiety-like behaviors in maternal and paternal lines of female rats. We used the "two hits, three generations apart" multigenerational exposure model to explore how two distinct EDCs-the weakly estrogenic PCB mixture Aroclor 1221 (A1221) and the antiandrogenic VIN-interact on behavior across generations. We also explored serum hormones as a potential mechanism. METHODS: Rats were prenatally exposed to A1221, VIN, or vehicle (DMSO) in the F1 generation, and a second exposure (same or different) was administered to the F4 generation. Anxiety-like behavior was measured in the Open Field test, Light:Dark box, and Elevated Plus Maze in the F1, F3, F4, and F6 generations. Serum concentrations of estradiol and corticosterone were analyzed. RESULTS: Behavioral effects were not detectable in the F1 generation but emerged and became more robust across generations. Rats with ancestral VIN exposure demonstrated less anxiety-like behavior in the F3 paternal line in comparison with controls. Rats exposed to ancestral then prenatal A1221/VIN and VIN/A1221 had more anxiety-like behavior in the F4 maternal line, and those with two ancestral hits of VIN/VIN had more anxiety in the F6 paternal line, in comparison with controls. DISCUSSION: Our findings suggest that anxiety-like behavioral phenotypes can manifest in rats following germline exposure to EDCs and that subsequent exposures across generations can intensify these effects in a lineage-dependent manner. https://doi.org/10.1289/EHP15621.

  PublisherDOI

Recent grants

• Functional and epigenetic effects of preconceptional EDCs on the female HPG axis

  NIH · $3.2M · 2019–2025

• NIH Grant R21ES012272

  NIH · $419k · 2007

• NIH Grant F32DK008743

  NIH · $81k

• NIH Grant R01ES020662

  NIH · $1.8M · 2017

• NIH Grant P01AG016765

  NIH · $39.5M · 2018

Frequent coauthors

• David Crews

  The University of Texas at Austin

  34 shared

• Lindsay M. Thompson

  The University of Texas at Austin

  25 shared

• Weiling Yin

  Jiangsu University

  22 shared

• Deena M. Walker

  Allen Institute for Brain Science

  22 shared

• Sarah M. Dickerson

  Walker (United States)

  16 shared

• Christoph Wanner

  University of Würzburg

  14 shared

• Martin Landray

  14 shared

• Ross Gillette

  The University of Texas at Austin

  14 shared

Education

• PhD, Neuroscience Training Program

  University of Wisconsin Madison

  1990

• A.B., Biology

  Princeton University

  1985