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| Status |
Public on Mar 07, 2020 |
| Title |
Gonadotropin surge-induced expression of progesterone receptor serves the ovary as a trigger of ovulation and a terminator of ovulatory inflammation |
| Organism |
Mus musculus |
| Experiment type |
Expression profiling by high throughput sequencing
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| Summary |
Ovulation is triggered by the gonadotropin surge that induces the expression of two key genes, progesterone receptor (Pgr) and prostaglandin-endoperoxide synthase 2 (Ptgs2) in the granulosa cells of preovulatory follicles. Their gene products PGR and PTGS2 activate two separate pathways that are both essential for successful ovulation. Here we show that the PGR plays an additional essential role; attenuate ovulatory inflammation by diminishing the gonadotropin surge-induced Ptgs2 expression. PGR indirectly terminates Ptgs2 expression and PGE2 synthesis in granulosa cells by inhibiting the NF-κB, a transcription factor required for Ptgs2 expression. When the expression of PGR was ablated in the granulosa cells, the ovary undergoes hyperinflammatory condition manifested by excessive PGE2 synthesis, immune cell infiltration, oxidative damage, and neoplastic transformation of ovarian cells. Despite the ovary undergoes ovulations dozens or hundreds of times in one’s lifetime, the repetitive ovulatory inflammations do not leave significant tissue damage in the ovary. The PGR-driven termination of PTGS2 expression may protect ovary from the ovulatory inflammation.
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| Overall design |
Wild type (Pgr flox/flox) and Esr2-driven Pgr conditional knockout (Esr2 iCre/wt Pgr flox/flox) mice were injected with PMSG at the age of 25 days after birth. On day 27, mice were injected with hCG to induce the superovulation. At 6h after hCG injection, 8 ovaries were collected from 4-different mice in each group and single-cell mRNA libraries were generated by Single-Cell 3’ Chromium kit version 3 from 10X Genomics.
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| Contributor(s) |
Park CJ, Lin P, Zhou S, Barakat R, Bashir ST, Choi JM, Cacioppo JA, Oakley OR, Duffy DM, Lydon JP, Ko CJ |
| Citation(s) |
32294429 |
| NIH grant(s) |
| Grant ID |
Grant title |
Affiliation |
Name |
| P01 HD071875 |
Mechanism of Periovulatory Leukocyte Infiltration into the Ovary |
UNIVERSITY OF KENTUCKY RESEARCH FOUNDATION |
CHEMYONG Jay KO |
| R21 HD094296 |
Conversion of ERalpha cells to ERbeta cells in a cell lineage |
UNIVERSITY OF ILLINOIS URBANA-CHAMPAIGN |
CHEMYONG Jay KO |
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| Submission date |
Feb 11, 2020 |
| Last update date |
May 18, 2020 |
| Contact name |
CheMyong Jay Ko |
| E-mail(s) |
jayko@illinois.edu
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| Organization name |
University of Illinois at Urbana Champaign
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| Department |
Comparative Biosciences
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| Street address |
2001 S. Lincoln Ave.
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| City |
Urbana |
| State/province |
Illinois |
| ZIP/Postal code |
61802 |
| Country |
USA |
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| Platforms (1) |
| GPL24247 |
Illumina NovaSeq 6000 (Mus musculus) |
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| Samples (2) |
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| Relations |
| BioProject |
PRJNA606048 |
| SRA |
SRP248225 |
| Supplementary file |
Size |
Download |
File type/resource |
| GSE145107_RAW.tar |
107.5 Mb |
(http)(custom) |
TAR (of TAR) |
SRA Run Selector |
| Raw data are available in SRA |
| Processed data provided as supplementary file |
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