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Characterization of estrogen and the endocrine-disrupting chemical-induced mouse mammary gland reorganization

ABSTRACT: This SuperSeries is composed of the SubSeries listed below.

ORGANISM(S): Mus musculus Homo sapiens

PROVIDER: GSE228190 | GEO | 2023/03/24

REPOSITORIES: GEO

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Single-cell RNA-sequencing analysis of estrogen- and endocrine-disrupting chemical-induced reorganization of mouse mammary gland.

Project description:Menopause is a critical window of susceptibility for its sensitivity to endocrine disrupting chemicals due to the decline of endogenous estrogen. Using a surgical menopausal (ovariectomized) mouse model, we assessed how mammary tissue was affected by both 17?-estradiol (E2) and polybrominated diphenyl ethers (PBDEs). As flame retardants in household products, PBDEs are widely detected in human serum. During physiologically-relevant exposure to E2, PBDEs enhanced E2-mediated regrowth of mammary glands with terminal end bud-like structures. Analysis of mammary gland RNA revealed that PBDEs both augmented E2-facilitated gene expression and modulated immune regulation. Through single-cell RNA sequencing (scRNAseq) analysis, E2 was found to induce Pgr expression in both Esr1 + and Esr1 - luminal epithelial cells and Ccl2 expression in Esr1 + fibroblasts. PBDEs promote the E2-AREG-EGFR-M2 macrophage pathway. Our findings support that E2?+?PBDE increases the risk of developing breast cancer through the expansion of estrogen-responsive luminal epithelial cells and immune modulation.

| S-EPMC6831695 | biostudies-literature

Characterization of estrogen and the endocrine-disrupting chemical-induced mouse mammary gland reorganization via bulk RNA-sequencing

Project description:Similar to the scRNA-Seq data (GSE125272), a surgical menopausal (ovariectomized) mouse model was used to assess how mammary gland tissue was affected by both 17β-estradiol (E2) and polybrominated diphenyl ethers (PBDEs). The PBDE treatments include three analyzed flame retardants: BDE-47, BDE-100 and BDE-153. Bulk RNA-Seq data was created with treatment conditions lasting 1 week. Gene expression changes for PBDE treatment are relatively small compared to E2 treatment. However, along with other studies and experiments, this data is meant to contribute to greater understanding of the interaction of PBDE exposure and estrogen signaling.

2023-03-24 | GSE227872 | GEO

Characterization of estrogen and the endocrine-disrupting chemical-induced mouse mammary gland reorganization via single-cell RNA-sequencing

Project description:Exposure to estrogen and its mimics during menopausal transition is thought to modify the structure of mammary gland. Using a surgical menopausal (ovariectomized) mouse model, we assessed how mammary gland tissue was affected by both 17β-estradiol (E2) and polybrominated diphenyl ethers (PBDEs). Three analyzed flame retardants, BDE-47, BDE-100 and BDE-153, are most frequently detected in human serum from all over the world. During physiologically-relevant exposure to E2, PBDEs enhanced E2-mediated regrowth of mammary glands with terminal end bud-like structures. According to sequencing analysis of mammary gland RNA, PBDEs both augmented E2-facilitated cell proliferationgene expression changes and modulated immune regulation. To better elucidate the effects of E2 and PBDEs, single-cell RNA sequencing (scRNAseq) analysis was performed. In a definitive manner, E2 was found to induce Pgr expression in both Esr1+ and Esr1- cells. Significantly, molecular evidence was available to show functional differences among cells with differential expression of Esr1 and Pgr. The PBDEs + E2 treatment increased the number of double positive (Esr1+Pgr+) and Pgr only (Esr1-Pgr+) cells in both mature luminal epithelial and progenitor cells of luminal epithelialcells. Moreover, the combination increased the mammary gland population of M2 macrophages. The results help clarify how exposure to both E2 and endocrine disrupting chemicals like PBDEs during menopausal transition impact mammary gland structure. Ultimately, the findings advance understanding of how exposure can increase the risk of developing breast cancer.

2019-11-12 | GSE125272 | GEO

Characterization of estrogen, progesterone and the endocrine-disrupting chemical-induced mouse mammary gland reorganization via single-cell RNA-sequencing

Project description:The mammary epithlium goes through the drastic reorganization during development, pregnancy, and menopause as well as by external hormones and its mimicry, which risks the gland for the specific type of breast cancer. Using a surgical menopausal (ovariectomized) mouse model, we assessed how mammary gland tissue was affected by 17β-estradiol (E2), progesterone (P4) and polybrominated diphenyl ethers (PBDEs). Then, we integrated the transcriptomes of 50K mouse and 24K human mammary epithelial cells from five different datasets and four individuals obtained by single-cell RNA sequencing (scRNAseq). The results indicated a putative trajectory originating from the embryonic mammary stem cells and differentiating into the three different epithelial lineage (Basal, Luminal alveolar, and Luminal hormone sensing) that were presumably sustained by unipotent progenitors in the postnatal glands. The identified lineage-specific gene sets inferred cells of origin of breast cancer using The Cancer Genome Atlas data and scRNAseq of human breast cancer. The comprehensive mammary cell atlas presented novel insights into the impact of the internal and external stimulati on the mammary epithelium in an unprecedented resolution.

2021-03-18 | GSE149949 | GEO

Characterization of estrogen and the endocrine-disrupting chemical-induced mouse mammary gland reorganization

Project description:Characterization of estrogen and the endocrine-disrupting chemical-induced mouse mammary gland reorganization

| PRJNA948456 | ENA

Characterization of estrogen and the endocrine-disrupting chemical-induced mouse mammary gland reorganization via bulk RNA-sequencing

Project description:Characterization of estrogen and the endocrine-disrupting chemical-induced mouse mammary gland reorganization via bulk RNA-sequencing

| PRJNA947213 | ENA

Characterization of estrogen and the endocrine-disrupting chemical-induced mouse mammary gland reorganization via single-cell RNA-sequencing

Project description:Characterization of estrogen and the endocrine-disrupting chemical-induced mouse mammary gland reorganization via single-cell RNA-sequencing

| PRJNA515727 | ENA

Characterization of estrogen, progesterone and the endocrine-disrupting chemical-induced mouse mammary gland reorganization via single-cell RNA-sequencing

Project description:Characterization of estrogen, progesterone and the endocrine-disrupting chemical-induced mouse mammary gland reorganization via single-cell RNA-sequencing

| PRJNA630686 | ENA

Characterization of effects of estrogen, progesterone and the endocrine-disrupting chemicals on mouse mammary gland in 4-vinylcyclohexene diepoxide-induced menopause model via single-cell RNA-sequencing

Project description:Mammary gland is a dynamic organ which undergoes most of its structural development after birth under cyclic control of ovarian hormones such as estrogen and progesterone. Using 4-vinylcyclohexene diepoxide (VCD) menopause model, we investigated the effect of ovarian hormones on mouse mammary glands. In particular, we focused on mouse mammary gland fibroblasts because they are one of the known crucial players but yet to be characterized well. With integrated analysis including six other publicly available datasets as well as mammary epithelium atlas data, we comprehensively described the characters of mouse mammary gland (e.g. potential commitment to mammary gland development, response to estrogens, developmental relationship, and crosstalk with mammary epithelium) in a population specific manner. Furthermore, we investigated the effect of endocrine disrupting chemical named polybrominated diphenyl ethers (PBDEs) in either of absence or presence of ovarian hormones on whole cellular components of mouse mammary gland including epithelial cells, fibroblasts, and immune cells at a single cell level.

2022-02-08 | GSE191219 | GEO

Estrogen-induced immune changes within the normal mammary gland.

Project description:Breast cancer (BCa) incidence increases following aberrant hormone exposure, which has been linked to direct effects on estrogen receptor (ER)+ mammary epithelium. While estrogen exposure during mammary involution has been shown to drive tumour growth via neutrophils, the potential for the ER + immune microenvironment to mediate part (in addition to mammary epithelial cells) of hormonally controlled BCa risk during normal development has not been assessed. We collected mammary tissue, lymph nodes and blood from tumour naïve mice treated with, oophorectomy, estrogen (17β estradiol) or Fulvestrant. Flow cytometry was used to examine the impact on the frequency of innate and adaptive immune cells. Oophorectomy and fulvestrant decreased the proportion of macrophages, particularly pro-tumour polarized M2 macrophages and neutrophils. Conversely, dendritic cells were increased by these therapies, as were eosinophils. Estrogen increased the proportion of M2 macrophages and to a lesser extent CD4-CD8- double negative and FoxP3+ regulatory T cells but decreased CD8 + T cells and B cells. Excluding eosinophils, these changes were restricted to the mammary tissue. This suggests that inhibiting estrogen action lowers the immune suppressive myeloid cells, increases in antigen presentation and eosinophil-mediated direct or indirect cytotoxic effects. In contrast, estrogen exposure, which drives BCa risk, increases the suppressive myeloid cells and reduces anti-tumour cytotoxic T cells. The impact of hormonal exposure on BCa risk, may in part be linked to its immune modulatory activity.

| S-EPMC9643548 | biostudies-literature

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