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ER beta regulated transcriptome in endometriotic tissues

ABSTRACT: The Estrogen Receptor beta (ERβ) has an essential role in endometriosis progression. However, the molecular mechanism of how ERβ drives endometriosis progression is not elucidated, yet. To define the role of genomic ERβ in endometriosis progression, we have employed whole-genome microarray expression profiling as a discovery platform to identify ERβ-regulated transcriptome in endometriotic tissues. To get this transcriptome, we applied endometrium specific ERβ overexpression (ERBOE) mouse model by crossing mouse having a pCAG promoter-loxPSTOPloxP-ERβ cassette with PRCre knockin mice that Cre recombinase cDNA was inserted into exon 1 of PR gene. Endometriosis was surgically induced in ERBOE mice and PRCre mice as the control by transplantation of uterine tissues. The ectopic lesions and eutopic endometrium were harvested at the estrus cycle in 4th weeks after endometriosis induction.

ORGANISM(S): Mus musculus

PROVIDER: GSE114010 | GEO | 2019/09/12

REPOSITORIES: GEO

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Project description:Endometriosis is associated with aberrant gene expression in the eutopic endometrium of women with disease. To determine if the development of endometriotic lesions directly impacts eutopic endometrial gene expression, we sequentially analyzed the eutopic endometrium across the time course of disease progression in a baboon model of induced disease. Endometriosis was induced in baboons by intraperitoneal inoculation of autologous menstrual endometrium. Eutopic endometria were collected at 9-11 days postovulation) in five time points: 1, 3, 6-7, 10-12, and 15-16 months after disease induction and compared with tissue from disease-free baboons. We used microarrays to identify differentially expressed genes between time points. Sequential analysis of the same animals during disease progression demonstrated an early disease insult and a transitory dominance of an estrogenic phenotype. However, as the disease progressed, a progesterone-resistant phenotype became evident. Endometriosis was experimentally induced in Papio anubis female baboons (n = 4) by intraperitoneal inoculation with menstrual endometrium on two consecutive menstrual cycles. Baboons with spontaneous endometriosis (n = 2) were also included in this study with an unknown duration of disease. Control endometrium was similarly harvested from animals (n = 4) with no previous surgeries and with no visible disease. The progression of disease was monitored in each animal by consecutive laparoscopies and video recording at 1 (n = 2), 3 (n = 4), 6-7 (n = 4), 10-12, (n = 4), and 15-16 (n = 3) months after inoculation during a window of 9-11 days postovulation. Eutopic endometrial tissues were harvested and were snap frozen in liquid nitrogen for RNA extraction. Additionally, menstrual endometrium was harvested on Days 1-2 of menses using a Unimar Pipelle (Cooper Surgical Inc., Shelton, CT) immediately prior to laparoscopy. Blood samples were collected daily from days 7 through 16 postmenstruation of menstrual cycles.

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ER beta regulated transcriptome in endometriotic tissues

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