PMID- 25225411
OWN - NLM
STAT- MEDLINE
DCOM- 20150430
LR  - 20231213
IS  - 1091-6490 (Electronic)
IS  - 0027-8424 (Print)
IS  - 0027-8424 (Linking)
VI  - 111
IP  - 39
DP  - 2014 Sep 30
TI  - Loss of BMAL1 in ovarian steroidogenic cells results in implantation failure in 
      female mice.
PG  - 14295-300
LID - 10.1073/pnas.1209249111 [doi]
AB  - The circadian clock plays a significant role in many aspects of female 
      reproductive biology, including estrous cycling, ovulation, embryonic 
      implantation, onset of puberty, and parturition. In an effort to link 
      cell-specific circadian clocks to their specific roles in female reproduction, we 
      used the promoter that controls expression of Steroidogenic Factor-1 (SF1) to 
      drive Cre-recombinase-mediated deletion of the brain muscle arnt-like 1 (Bmal1) 
      gene, known to encode an essential component of the circadian clock 
      (SF1-Bmal1(-/-)). The resultant SF1-Bmal1(-/-) females display embryonic 
      implantation failure, which is rescued by progesterone supplementation, or 
      bilateral or unilateral transplantation of wild-type ovaries into SF1-Bmal1(-/-) 
      dams. The observation that the central clock, and many other peripheral clocks, 
      are fully functional in this model allows the assignment of the implantation 
      phenotype to the clock in ovarian steroidogenic cells and distinguishes it from 
      more general circadian related systemic pathology (e.g., early onset arthropathy, 
      premature aging, ovulation, late onset of puberty, and abnormal estrous cycle). 
      Our ovarian transcriptome analysis reveals that deletion of ovarian Bmal1 
      disrupts expression of transcripts associated with the circadian machinery and 
      also genes critical for regulation of progesterone production, such as 
      steroidogenic acute regulatory factor (Star). Overall, these data provide a 
      powerful model to probe the interlocking and synergistic network of the circadian 
      clock and reproductive systems.
FAU - Liu, Yan
AU  - Liu Y
AD  - McArdle Laboratory for Cancer Research, and Carbone Cancer Center, School of 
      Medicine and Public Health, University of Wisconsin-Madison, Madison WI 53706;
FAU - Johnson, Brian P
AU  - Johnson BP
AD  - McArdle Laboratory for Cancer Research, and Carbone Cancer Center, School of 
      Medicine and Public Health, University of Wisconsin-Madison, Madison WI 53706;
FAU - Shen, Anna L
AU  - Shen AL
AD  - McArdle Laboratory for Cancer Research, and Carbone Cancer Center, School of 
      Medicine and Public Health, University of Wisconsin-Madison, Madison WI 53706;
FAU - Wallisser, Jacqueline A
AU  - Wallisser JA
AD  - McArdle Laboratory for Cancer Research, and Carbone Cancer Center, School of 
      Medicine and Public Health, University of Wisconsin-Madison, Madison WI 53706;
FAU - Krentz, Kathy J
AU  - Krentz KJ
AD  - McArdle Laboratory for Cancer Research, and Carbone Cancer Center, School of 
      Medicine and Public Health, University of Wisconsin-Madison, Madison WI 53706;
FAU - Moran, Susan M
AU  - Moran SM
AD  - McArdle Laboratory for Cancer Research, and Carbone Cancer Center, School of 
      Medicine and Public Health, University of Wisconsin-Madison, Madison WI 53706;
FAU - Sullivan, Ruth
AU  - Sullivan R
AD  - McArdle Laboratory for Cancer Research, and Carbone Cancer Center, School of 
      Medicine and Public Health, University of Wisconsin-Madison, Madison WI 53706; 
      Research Animal Resources Center, University of Wisconsin-Madison, Madison, WI 
      53706; and.
FAU - Glover, Edward
AU  - Glover E
AD  - McArdle Laboratory for Cancer Research, and Carbone Cancer Center, School of 
      Medicine and Public Health, University of Wisconsin-Madison, Madison WI 53706;
FAU - Parlow, Albert F
AU  - Parlow AF
AD  - National Hormone and Peptide Program, Harbor-University of California Los Angeles 
      Medical Center, Torrance, CA 90502.
FAU - Drinkwater, Norman R
AU  - Drinkwater NR
AD  - McArdle Laboratory for Cancer Research, and Carbone Cancer Center, School of 
      Medicine and Public Health, University of Wisconsin-Madison, Madison WI 53706;
FAU - Schuler, Linda A
AU  - Schuler LA
AD  - Carbone Cancer Center, School of Medicine and Public Health, University of 
      Wisconsin-Madison, Madison WI 53706; Department of Comparative Biosciences, 
      School of Veterinary Medicine, University of Wisconsin-Madison, Madison WI 53706;
FAU - Bradfield, Christopher A
AU  - Bradfield CA
AD  - McArdle Laboratory for Cancer Research, and Carbone Cancer Center, School of 
      Medicine and Public Health, University of Wisconsin-Madison, Madison WI 53706; 
      bradfield@oncology.wisc.edu.
LA  - eng
SI  - GEO/GSE48758
GR  - P30 CA014520/CA/NCI NIH HHS/United States
GR  - R37 ES005703/ES/NIEHS NIH HHS/United States
GR  - T32 ES007015/ES/NIEHS NIH HHS/United States
GR  - T32ES007015-32/ES/NIEHS NIH HHS/United States
GR  - R37ES005703/ES/NIEHS NIH HHS/United States
PT  - Journal Article
PT  - Research Support, N.I.H., Extramural
DEP - 20140915
PL  - United States
TA  - Proc Natl Acad Sci U S A
JT  - Proceedings of the National Academy of Sciences of the United States of America
JID - 7505876
RN  - 0 (ARNTL Transcription Factors)
RN  - 0 (Bmal1 protein, mouse)
RN  - 0 (Steroidogenic Factor 1)
RN  - 0 (Steroids)
RN  - 0 (steroidogenic factor 1, mouse)
RN  - 4G7DS2Q64Y (Progesterone)
SB  - IM
CIN - Nat Rev Endocrinol. 2014 Dec;10(12):701. PMID: 25287286
MH  - ARNTL Transcription Factors/*deficiency/genetics/*physiology
MH  - Aging/genetics/physiology
MH  - Animals
MH  - Circadian Rhythm/genetics/physiology
MH  - Embryo Implantation/drug effects/genetics/*physiology
MH  - Estrus/genetics/physiology
MH  - Female
MH  - Gene Expression Profiling
MH  - Male
MH  - Mice
MH  - Mice, Inbred C57BL
MH  - Mice, Knockout
MH  - Ovary/*cytology/*physiology/transplantation
MH  - Pregnancy
MH  - Progesterone/administration & dosage
MH  - Promoter Regions, Genetic
MH  - Sexual Maturation/genetics/physiology
MH  - Steroidogenic Factor 1/genetics
MH  - Steroids/*biosynthesis
PMC - PMC4191810
OTO - NOTNLM
OT  - circadian rhythm
OT  - fertility
OT  - ovary
OT  - steroidogenesis
COIS- The authors declare no conflict of interest.
EDAT- 2014/09/17 06:00
MHDA- 2015/05/01 06:00
PMCR- 2014/09/15
CRDT- 2014/09/17 06:00
PHST- 2014/09/17 06:00 [entrez]
PHST- 2014/09/17 06:00 [pubmed]
PHST- 2015/05/01 06:00 [medline]
PHST- 2014/09/15 00:00 [pmc-release]
AID - 1209249111 [pii]
AID - 201209249 [pii]
AID - 10.1073/pnas.1209249111 [doi]
PST - ppublish
SO  - Proc Natl Acad Sci U S A. 2014 Sep 30;111(39):14295-300. doi: 
      10.1073/pnas.1209249111. Epub 2014 Sep 15.