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Status |
Public on Jan 07, 2019 |
Title |
Chemotherapeutic agent doxorubicin alters uterine gene expression in response to estrogen in ovariectomized CD-1 adult mice |
Organism |
Mus musculus |
Experiment type |
Expression profiling by high throughput sequencing
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Summary |
Chemotherapy can potentially impair fertility in premenopausal cancer patients. Female fertility preservation has been mainly focused on the ovarian aspects and benefited greatly from assisted reproductive technologies, such as in vitro fertilization (IVF). The rate-limiting step for the success of IVF is embryo implantation in the uterus. Doxorubicin (DOX) is a widely used chemotherapeutic agent with ovarian toxicity. It remains unknown if the uterus is a direct target of DOX. To circumvent the indirect uterine effect from ovarian toxicity of DOX and to investigate potential long-term impact of DOX on the uterus, young adult ovariectomized CD-1 mice were given an intraperitoneal injection once with PBS or DOX (10 mg/kg, a human relevant chemotherapeutic dose), and 30 days later, each set of mice was randomly assigned into three groups and subcutaneously injected with oil, 17β-estradiol (E2, for 6 hours), and progesterone (P4, for 54 hours), respectively. Uterine transcriptomic profiles were determined using RNA-seq. Principal component analysis of the uterine transcriptomes revealed four clusters from the six treatment groups: PBS-oil & DOX-oil, PBS-P4 & DOX-P4, PBS-E2, and DOX-E2, indicating that DOX treatment did not affect the overall uterine transcriptomic profiles in the oil and P4-treated mice but altered uterine responses to E2 treatment. These data demonstrate that DOX can directly target the uterus and has a long-term impact on uterine responses to E2.
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Overall design |
Examination of the uterine transcriptome upon DOX or vehicle treatment
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Contributor(s) |
Andersen CL, Liu M, Wang Z, Ye X, Xiao S |
Citation(s) |
30561525 |
NIH grant(s) |
Grant ID |
Grant title |
Affiliation |
Name |
P01 ES028942 |
Interactions of Climate Change on Oceans and Human Health: Assessment of Effects on Ocean Health Related Illness and Disease and Development of Prevention Strategies to Better Protect Public Health |
UNIVERSITY OF SOUTH CAROLINA |
Geoffrey Ivan Scott |
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Submission date |
Dec 17, 2018 |
Last update date |
Mar 25, 2019 |
Contact name |
Christian Andersen |
E-mail(s) |
cla71@uga.edu
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Organization name |
University of Georgia
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Department |
Physiology and Pharmacology
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Lab |
YE LAB
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Street address |
501 D.W. Brooks Dr., Physiology and Pharmacology
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City |
Athens |
State/province |
Georgia |
ZIP/Postal code |
30602 |
Country |
USA |
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Platforms (1) |
GPL19057 |
Illumina NextSeq 500 (Mus musculus) |
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Samples (18)
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Relations |
BioProject |
PRJNA510374 |
SRA |
SRP173624 |