June 18, 2007 The hormone progesterone is vital to ovulation and pregnancy, however various aspects of its roles throughout pregnancy are not well understood. A hurdle to expanding our knowledge of the effects of progesterone is the fact that progesterone-deficient mice cannot produce offspring. However, as FKBP52 is a molecule that acts to optimize signaling through the progesterone receptor, Fkbp52-/- mice provide a unique opportunity to study the roles of progesterone signaling throughout pregnancy.
Sudhansu Dey and colleagues from Vanderbilt University first established that embryo implantation in the uterus in female Fkbp52-/- mice was not successful, mimicking the effect of the loss of progesterone, however daily progesterone supplementation enabled successful implantation of embryos in female Fkbp52-/- mice of one genetic background (referred to as C57BL6/129 Fkbp52-/- mice), but not another (CD1 Fkbp52-/- mice). The results indicate that FKBP52 deficiency-induced loss of uterine progesterone signaling is genetic background-specific.
The authors went on to show that while progesterone supplementation at higher than normal pregnancy levels enabled progesterone receptor signaling sufficient for embryo implantation in the uterus in female CD1 Fkbp52-/- mice, these levels were not sufficient to maintain pregnancy to full term. Progesterone levels had to be further elevated to achieve successful term pregnancy and a normal litter size.
In summary, the data reflect that the indispensability of FKBP52 in uterine progesterone signaling is genetic background- and pregnancy stage-specific. As there is evidence of a correlation between progesterone supplementation and a reduction in the risk of recurrent miscarriages and endometriosis in progesterone-deficient women, these findings have clinical implications for a genetically diverse population of women.
Reference: FKBP52 deficiency-conferred uterine progesterone resistance is genetic background and pregnancy stage specific, online on June 14 in advance of publication in the July print issue of the Journal of Clinical Investigation.
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