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| Status |
Public on Feb 01, 2013 |
| Title |
Targeted disruption of BMAL1 in the peripheral reproductive axis results in infertility in female mice. |
| Organism |
Mus musculus |
| Experiment type |
Expression profiling by array
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| Summary |
The product of the Bmal1 locus is an essential component of the circadian clock that plays important roles in various aspects of reproductive biology, and its disruption results in infertility. In an effort to identify the identity of the tissue specific clock that is responsible for this infertility, we used the steroidogenic factor-1 (Sf1) promoter to drive Cre-mediated recombination and genetically delete Bmal1 within cells of the reproductive axis. We show that Bmal1 within the reproductive axis of females is essential for normal fertility through its role in maintaining implantation, but is not required for normal estrous cycling. At the root of this biology appears to be a defect in the regulation of ovarian steroidogenic acute regulator (StAR) and its role in maintaining progesterone synthesis. This conclusion is based upon three observations. First, that deletion of Bmal1 within the reproductive axis leads to lower levels of StAR mRNA, and lower progesterone levels. Second, that progesterone supplementation of these conditional mutants rescues implantation. Third, transplantation of wild type ovaries into Bmal1 reproductive axis mutants results in 100% fertility. Our study suggests that ovarian Bmal1 is an essential peripheral clock governing implantation and fertility in female mice.
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| Overall design |
Ten week old female Bmal1fxfx mice positive or negative for Cre-recombinase driven by the sf-1 promoter, housed in 12 hour light:12 dark, ad lib feeding and drinking conditions were sacrificed at ZT12 on 3.5dpc (3.5 days post copulation). For each array analysis, a pool of 3 RNA samples from 3 individual Bmal1fx/fxCresf-1 ovaries labeled with cy3 were co-hybridized with a pool of 3 RNA samples from Bmal1fx/fx ovaries labeled with cy5, according to Agilent protocols.
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| Contributor(s) |
Johnson BP, Liu Y, Bradfield CA |
| Citation missing |
Has this study been published? Please login to update or notify GEO. |
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| Submission date |
May 31, 2012 |
| Last update date |
May 10, 2018 |
| Contact name |
Brian P Johnson |
| Phone |
608-262-1209
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| Organization name |
UW-Madison
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| Department |
Oncology
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| Lab |
Chris Bradfield
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| Street address |
1400 University Ave
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| City |
Madison |
| State/province |
WI |
| ZIP/Postal code |
53706 |
| Country |
USA |
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| Platforms (1) |
| GPL4134 |
Agilent-014868 Whole Mouse Genome Microarray 4x44K G4122F (Feature Number version) |
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| Samples (3) |
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| Relations |
| BioProject |
PRJNA167747 |
