Susanne Tranguch, Haibin Wang, Takiko Daikoku, Huirong Xie, David F. Smith, Sudhansu K. Dey
J Clin Invest.
2007;
117(7):1824–1834
doi:10.1172/JCI31622
This article Copyright © 2007, The American Society for Clinical Investigation
Abstract
|
Full text
|
PDF
|
Supplemental material
I
mmunophilin FKBP52 serves as a cochaperone to govern normal progesterone (P4) receptor (PR) function. Using Fkbp52–/– mice, we show intriguing aspects of uterine P4/PR signaling during pregnancy. Implantation failure is the major phenotype found in these null females, which is conserved on both C57BL6/129 and CD1 backgrounds. However, P4 supplementation rescued implantation and subsequent decidualization in CD1, but not C57BL6/129, null females. Surprisingly, experimentally induced decidualization in the absence of blastocysts failed in Fkbp52–/– mice on either background even with P4 supplementation, suggesting that embryonic signals complement uterine signaling for this event. Another interesting finding was that while P4 at higher than normal pregnancy levels conferred PR signaling sufficient for implantation in CD1 null females, these levels were inefficient in maintaining pregnancy to full term. However, elevating P4 levels further restored PR signaling to a level optimal for successful term pregnancy with normal litter size. Collectively, the results show that the indispensability of FKBP52 in uterine P4/PR signaling is a function of genetic disparity and is pregnancy stage specific. Since there is evidence for a correlation between P4 supplementation and reduced risks of P4-resistant recurrent miscarriages and remission of endometriosis, these findings have clinical implications for genetically diverse populations of women.
This file is in Adobe Acrobat (PDF) format.
If you have not installed and configured the Adobe Acrobat Reader on your system.
Having trouble reading a PDF?
PDFs are designed to be printed out and read, but if you prefer to read them online, you may find it easier if you increase the view size to 125%.
Having trouble saving a PDF?
Many versions of the free Acrobat Reader do not
allow Save. You must instead save the PDF from the JCI Online page you downloaded it from. PC users:
Right-click on the Download link and choose the option that says something like "Save Link As...".
Mac users should hold the mouse button down on the link to get these same options.
Having trouble printing a PDF?
- Try printing one page at a time or to a newer printer.
- Try saving the file to disk before printing rather than opening it "on the fly." This requires that you
configure your browser to "Save" rather than "Launch Application" for the file type "application/pdf", and can
usually be done in the "Helper Applications" options.
- Make sure you are using the latest version of Adobe's Acrobat Reader.
