Estrogen Receptor Alpha (ESR1)-Dependent Regulation of the Mouse Oviductal Transcriptome

• Published in: PloS one Vol. 11; no. 1; p. e0147685
• Main Authors: Cerny, Katheryn L, Ribeiro, Rosanne A C, Jeoung, Myoungkun, Ko, CheMyong, Bridges, Phillip J
• Format: Journal Article
• Language: English
• Published: United States Public Library of Science 25-01-2016; Public Library of Science (PLoS)
• Subjects: 17β-Estradiol; Age; Animal care; Animals; Biological activity; Biology and Life Sciences; Catalysis; Catalytic activity; Categories; Chlamydia; Chlamydia trachomatis; Clonal deletion; Computational Biology; Cytokines; DNA microarrays; Enrichment; Estradiol; Estrogen Receptor alpha - genetics; Estrogen Receptor alpha - metabolism; Estrogen receptors; Estrogens; Fallopian Tubes - metabolism; Female; Females; Fertility; Gene expression; Genes; Genetic aspects; Genomes; Genomics; Genotype; Genotypes; Hybridization; Immune response; Immune system; Infections; Lysergide; Medicine and Health Sciences; Mice; Mice, Knockout; Mice, Transgenic; Oviduct; Physiological aspects; Principal components analysis; Real-Time Polymerase Chain Reaction; Regulations; Research and Analysis Methods; Ribonucleic acid; RNA; Rodents; Sex hormones; Statistical analysis; Transcription; Transcriptome - genetics; Transgenic mice; Variance analysis; United States; United States > US
• ISSN: 1932-6203; 1932-6203
• DOI: 10.1371/journal.pone.0147685

Estrogen receptor-α (ESR1) is an important transcriptional regulator in the mammalian oviduct, however ESR1-dependent regulation of the transcriptome 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 ESR1. Oviducts were collected from ESR1KO and WT littermates at 23 days of age, or ESR1KO and WT mice were treated with 5 IU PMSG to stimulate follicular development and the production of ovarian estradiol, and the oviducts collected 48 h later. RNA extracted from whole oviducts was hybridized to Affymetrix Genechip Mouse Genome 430-2.0 arrays (n = 3 arrays per genotype and treatment) or reverse transcribed to cDNA for analysis of the expression of selected mRNAs by real-time PCR. Following microarray analysis, a statistical two-way ANOVA and pairwise comparison (LSD test) revealed 2428 differentially expressed transcripts (DEG's, P < 0.01). Genotype affected the expression of 2215 genes, treatment (PMSG) affected the expression of 465 genes, and genotype x treatment affected the expression of 438 genes. With the goal of determining estradiol/ESR1-regulated function, gene ontology (GO) and bioinformatic pathway analyses were performed on DEG's in the oviducts of PMSG-treated ESR1KO versus PMSG-treated WT mice. Significantly enriched GO molecular function categories included binding and catalytic activity. Significantly enriched GO cellular component categories indicated the extracellular region. Significantly enriched GO biological process categories involved a single organism, modulation of a measurable attribute and developmental processes. Bioinformatic analysis revealed ESR1-regulation of the immune response within the oviduct as the primary canonical pathway. In summary, a transcriptomal profile of estradiol- and ESR1-regulated gene expression and related bioinformatic analysis is presented to increase our understanding of how estradiol/ESR1 affects function of the oviduct, and to identify genes that may be proven as important regulators of fertility in the future.