A5065654048- Estrogen and related hormone effects
- Effects and risks of endocrine disrupting chemicals
- Reproductive System and Pregnancy
- Cancer Cells and Metastasis
- Epigenetics and DNA Methylation
- RNA modifications and cancer
- Birth, Development, and Health
- Cancer Risks and Factors
- Protein Kinase Regulation and GTPase Signaling
- Toxic Organic Pollutants Impact
- Digital Transformation in Law
- Nutrition, Genetics, and Disease
- Nitric Oxide and Endothelin Effects
- Glycosylation and Glycoproteins Research
- Per- and polyfluoroalkyl substances research
- Genomics and Phylogenetic Studies
- RNA Research and Splicing
- Science, Research, and Medicine
- Mechanisms of cancer metastasis
- Reproductive Biology and Fertility
- Genomics and Chromatin Dynamics
- Protein Tyrosine Phosphatases
- Mitochondrial Function and Pathology
- Human Health and Disease
- RNA and protein synthesis mechanisms
National Institute of Environmental Health Sciences
2016-2023
National Institutes of Health
2018-2023
Research Triangle Park Foundation
2018-2019
Environmental Protection Agency
2018-2019
Oak Ridge Institute for Science and Education
2019
University of North Carolina at Chapel Hill
2013-2017
University of North Carolina Health Care
2016
University of California, Davis
2013
Abstract The oncofetal protein sine oculis-related homeobox 1 (SIX1) is a developmental transcription factor associated with carcinogenesis in several human cancer types but has not been investigated endometrial cancer. In model of hormonal carcinogenesis, mice neonatally exposed to the soy phytoestrogen genistein (GEN) or synthetic estrogen diethylstilbestrol (DES) develop as adults. Previously, we demonstrated that SIX1 becomes aberrantly expressed uteri these mice. Here, used this mouse...
Tissue development entails genetically programmed differentiation of immature cell types to mature, fully differentiated cells. Exposure during non-mutagenic environmental factors can contribute cancer risk, but the underlying mechanisms are not understood. We used a mouse model endometrial adenocarcinoma that results from brief developmental exposure an estrogenic chemical, diethylstilbestrol (DES), determine causative factors. Single-cell RNA sequencing (scRNAseq) and spatial...
Little is known regarding how steroid hormone exposures impact the epigenetic landscape in a living organism. Here, we took global approach to understanding exposure estrogenic chemical, diethylstilbestrol (DES), affects neonatal mouse uterine epigenome. Integration of RNA- and ChIP-sequencing data demonstrated that ∼80% DES-altered genes had higher H3K4me1/H3K27ac signal close proximity. Active enhancers, which ∼3% were super-enhancers, high density estrogen receptor alpha (ERα) binding...
Abstract Early-life exposure to estrogenic chemicals can increase cancer risk, likely by disrupting normal patterns of cellular differentiation. Female mice exposed neonatally the synthetic estrogen diethylstilbestrol (DES) develop metaplastic and neoplastic uterine changes as adults. Abnormal endometrial glands express oncofetal protein sine oculis homeobox 1 (SIX1) contain cells with basal [cytokeratin (CK)14+/18−] poorly differentiated features (CK14+/18+), strongly associating SIX1...
Embryo implantation relies on precise hormonal regulation, associated gene expression changes, and appropriate female reproductive tract tissue architecture. Female mice exposed neonatally to the phytoestrogen genistein (GEN) at doses similar those in infants consuming soy-based infant formulas are infertile due part uterine defects.
Developmental exposure to estrogenic chemicals is an established risk factor for cancer of the female reproductive tract. This increase in has been associated with disruption normal patterns cellular differentiation during critical stages morphogenesis. The goal this study was document uterine epithelial phenotypes over time following neonatal treatment synthetic estrogen diethylstilbestrol (DES) or soy phytoestrogen genistein (GEN) CD-1 mice. Both DES and GEN induced three distinct...
During the past 20 years, investigations involving endocrine active substances (EAS) and reproductive toxicity have dominated landscape of ecotoxicological research. This has occurred in concert with heightened awareness scientific community, general public, governmental entities potential consequences chemical perturbation humans wildlife. The exponential growth experimentation this field is fueled by our expanding knowledge into complex nature systems intricacy their interactions...
Abstract Developmental exposure to non-mutagenic environmental factors can contribute cancer risk, but the underlying mechanisms are not understood. We used a mouse model of endometrial adenocarcinoma that results from brief developmental an estrogenic chemical, diethylstilbestrol (DES), determine causative factors. Single cell RNA sequencing and spatial transcriptomics adult uteri revealed new markers uterine epithelial stem cells, identified luminal glandular progenitor defined...
<p>Supplementary Figure S1. Six1 transcript and protein expression in Six 1conditional knockout mice following neonatal DES exposure. Supplementary S2. S3. S4. CK14/18 staining normal abnormal uterine epithelium.</p>
<p>Uterine abnormalities resulting from neonatal exposure to GEN or DES.</p>
<p>Supplementary Figure S1. Six1 transcript and protein expression in Six 1conditional knockout mice following neonatal DES exposure. Supplementary S2. S3. S4. CK14/18 staining normal abnormal uterine epithelium.</p>
<p>Uterine abnormalities resulting from neonatal exposure to GEN or DES.</p>
<div>Abstract<p>Early-life exposure to estrogenic chemicals can increase cancer risk, likely by disrupting normal patterns of cellular differentiation. Female mice exposed neonatally the synthetic estrogen diethylstilbestrol (DES) develop metaplastic and neoplastic uterine changes as adults. Abnormal endometrial glands express oncofetal protein sine oculis homeobox 1 (SIX1) contain cells with basal [cytokeratin (CK)14<sup>+</sup>/18<sup>−</sup>] poorly...
<div>Abstract<p>The oncofetal protein sine oculis-related homeobox 1 (SIX1) is a developmental transcription factor associated with carcinogenesis in several human cancer types but has not been investigated endometrial cancer. In model of hormonal carcinogenesis, mice neonatally exposed to the soy phytoestrogen genistein (GEN) or synthetic estrogen diethylstilbestrol (DES) develop as adults. Previously, we demonstrated that SIX1 becomes aberrantly expressed uteri these mice....