Project description:Estrogen receptor-α (ESR1) is an important transcriptional regulator in the mammalian oviduct, however ESR1-dependent regulation of this organ is not well defined, especially at the genomic level. The objective of this study was therefore to investigate estradiol- and ESR1-dependent regulation of the transcriptome of the oviduct using transgenic mice, both with (ESR1KO) and without (wild-type, WT) a global deletion of this transcription factor using the Affymetrix Genechip Mouse Genome 430-2.0 arrays.
Project description:Ciliary action performs a critical role in the oviduct (Fallopian tube), during pregnancy establishment through sperm and egg transport. The disruption of normal ciliary function in the oviduct affects oocyte pick-up and is a contributing factor to female infertility. Estrogen is an important regulator of ciliary action in the oviduct and promotes ciliogenesis in several species. Global loss of estrogen receptor 1 alpha (encoded by Esr1 gene) leads to infertility. Our laboratory has previously shown that ESR1 in the oviductal epithelial cell layer is required for female fertility. Here, we assessed the role of estrogen on transcriptional regulation of ciliated epithelial cells of the oviduct using single-cell RNA-sequencing analysis. We observed minor variations in ciliated cell genes in the proximal region (isthmus and uterotubal junction) of the oviduct. However, E2 treatment had little impact on the gene expression profile of ciliated epithelial cells. To assess the requirement of ESR1 specifically in ciliated cells for female fertility, we conditionally ablated Esr1 from ciliated epithelial cells of the oviduct (called ciliated Esr1d/d mice). Our studies showed that ciliated Esr1d/d females had fertility rates comparable to control females, did not display any disruptions in preimplantation embryo development or embryo transport to the uterus, and had comparable cilia formation to control females. However, we observed some incomplete deletion of Esr1 in the ciliated epithelial cells, especially in the ampulla region. Therefore, more studies are required to definitively determine ESR1 function in ciliated cells of the oviduct. Nevertheless, our data suggest that ESR1 expression in ciliated cells of the oviduct is dispensable for ciliogenesis, but nonessential for female fertility in mice. All genes expressed in scRNA-seq datasets are available for scientific community and separable at https://www.winuthayanon.com/genes/ve2h_cilia/ and https://www.winuthayanon.com/genes/ve2h_allclusters/
Project description:Purpose: To characterize the estrogen receptor α (ESR1)-dependent transcriptome of neurons in the arcuate nucleus that regulate female bone density
Project description:Affymetrix microarray data was generated from MCF7 breast cancer cells treated in vitro with siRNAs against estrogen receptor alpha (ESR1). Gene expresion of estrogen receptor alpha (ESR1) was knocked down in MCF7 breast cancer cells using siRNA. Then the gene expression profiles of these MCF7 cells, along with non-targetting control treated cells were analysed using Affymetrix Human Genome U133 Plus 2.0 microarrays.
Project description:<p>Reduced estrogen action is associated with obesity and insulin resistance. However, the cell and tissue-specific actions of estradiol in maintaining metabolic health remain inadequately understood, especially in men. We observed that skeletal muscle ESR1/Esr1 (encodes estrogen receptor α) is positively correlated with insulin sensitivity and metabolic health in humans and mice. Because skeletal muscle is a primary tissue involved in oxidative metabolism and insulin sensitivity, we generated muscle-selective Esr1 loss- and gain-of-expression mouse models. We determined that Esr1 links mitochondrial DNA replication and cristae-nucleoid architecture with metabolic function and insulin action in skeletal muscle of male mice. Overexpression of human ERα in muscle protected male mice from diet-induced disruption of metabolic health and enhanced mitochondrial adaptation to exercise training intervention. Our findings indicate that muscle expression of Esr1 is critical for the maintenance of mitochondrial function and metabolic health in males, and that tissue-selective activation of ERα can be leveraged to combat metabolic-related diseases in both sexes.</p>