Targeted disruption of BMAL1 in the peripheral reproductive axis results in infertility in female mice

ABSTRACT: 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 when disrupted results in infertility. In an effort to establish 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 ovaries, including regulation of ovarian lipid biosynthetic or metabolic processes and their roles in maintaining progesterone synthesis. This conclusion is based upon three observations. First, that deletion of Bmal1 within the reproductive axis reducesleads to affected transcripts in steroidogenic pathways for the LH receptor , and lowers progesterone levels. Second, that progesterone supplementation of these conditional mutants rescues implantation. Third, transplantation of wild type ovaries into Bmal1 reproductive axis mutants rescues fertility. Our study demonstrates the significance of ovarian Bmal1 as an overriding influence in experimental models of infertility. A time series was performed in time-mated C57Bl/6J mice to identiy oscillating transcripts. During the peak and trough of the majority of transcripts (ZT0 and ZT12) samples from Bmal1fx/fx Sf1Cre mice and control litermates as well and global Bmal1 nulls were also analyzed. The tissue types (ovary, pituitary) are not comparable.

ORGANISM(S): Mus musculus

SUBMITTER: Brian Johnson 

PROVIDER: E-GEOD-48758 | biostudies-arrayexpress |

REPOSITORIES: biostudies-arrayexpress