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Series GSE152675 Query DataSets for GSE152675
Status Public on Apr 23, 2021
Title Gene expression profiling of Smad1/5 cKO and Acvr2a cKO mice
Organism Mus musculus
Experiment type Expression profiling by high throughput sequencing
Summary We generated mice with single or double conditional inactivation of SMAD1 and SMAD5 using progesterone receptor (PR) cre (Smad1flox/flox;Smad5flox/flox;Pgr-cre+/-, or “Smad1/5 cKO”). Female mice with single SMAD1 or SMAD5 deletion were subfertile, whereas Smad1/5 cKO were infertile and had no visible implantation sites at 4.5 days post-coitum (dpc), indicating functional redundancy of SMAD1 and SMAD5. Histological and molecular analyses of the Smad1/5 cKO uteri during pregnancy determined that the infertility was the result of impaired uterine receptivity. During the window of implantation, uteri of Smad1/5 cKO mice responded abnormally to estradiol (E2) and to progesterone (P4), retained luminal PR expression, and displayed cytoplasmic FOXO1 mis-localization. Furthermore, uteri of Smad1/5 cKO mice did not respond to an artificial decidual stimulus and the stroma failed to differentiate. To determine the cell surface receptor complex that controls BMP signaling during implantation, we generated mice with conditional deletion of Acvr2a and Acvr2b using Pgr-cre+/-. We determined that Acvr2b cKO females were subfertile, while Acvr2a cKOs were infertile and displayed a range of ovarian and uterine abnormalities, including endometrial and implantation defects that phenocopied those of Smad1/5 cKO mice. Transcriptomic profiling of the Smad1/5 cKO and Acvr2a cKO uterus showed that genes involved in epithelial cell remodeling and microvilli/ciliated cell function were overrepresented in both genotypes. These results demonstrate that BMP signals mediated via ACVR2A and SMAD1/5 control endometrial receptivity and embryo implantation by remodeling the apicobasal polarity of the epithelium during the window of implantation.
Overall design Multiple group comparison
Contributor(s) Creighton C, Chen F, Monsivais D, Matzuk M
Citation(s) 34099644
Submission date Jun 17, 2020
Last update date Jun 15, 2021
Contact name Chad Creighton
Organization name Baylor College of Medicine
Department Biostatistics, Ducan Cancer Center
Street address One Baylor Plaza, Mail Stop: BCM305
City Houston
State/province TX
ZIP/Postal code 77030
Country USA
Platforms (1)
GPL24247 Illumina NovaSeq 6000 (Mus musculus)
Samples (11)
GSM4623141 FF Control_1
GSM4623142 FF Control_2
GSM4623143 FF Control_3
BioProject PRJNA640047
SRA SRP267659

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Supplementary file Size Download File type/resource
GSE152675_RAW.tar 9.9 Mb (http)(custom) TAR (of TXT)
SRA Run SelectorHelp
Raw data are available in SRA
Processed data provided as supplementary file

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