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Fertility study shows increased estrogen shortens window of implantation in mice

present would remain suspended in a kind of dormancy. It was at this stage that the researchers were able to parse estrogen's effect on the implantation process.

They found that a single injection of either 3, 10, or 25 nanograms of estrogen was capable of initiating implantation. However, injection of three nanograms of estrogen was enough to prolong uterine receptivity in the mice for up to four days. Increasing the estrogen dose to 10 nanograms rapidly closed the window of receptivity: within 24 hours, implantation no longer occurred. A second dose of estrogen, whether low or high, did not rescue receptivity after an initial high dose.

What's more remarkable, Dey says, is that the same sensitivity to progesterone doesn't seem to exist. "You can increase progesterone, say from one to four milligrams, and still, implantation would be fine," he said. "And a high progesterone level does not counteract this estrogen effect."

When the researchers looked at expression of a handful of key, implantation-specific genes at the site of blastocyst implantation, they found an abnormal pattern of activation in mice that received high doses of estrogen. Future studies may shed light on other gene expression changes, and on whether this effect is patchy or uniform in the uterus.

"It will be really interesting to see whether the gene expression pattern is changing from region to region within the uterus with changing estrogen levels," said Dey.

The applicability of these findings to humans is uncertain yet promising. Levels of estrogen in women undergoing in vitro fertilization rise due to the ovarian hyperstimulation required for retrieving multiple eggs. One prediction from their investigation, Dey says, is that exposure of the uterus to these increased estrogen levels may be contributing to high implantation failure rates.

Estrogen levels in women can be affected in other ways, as well, whether through the drugs or medications
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Contact: Clinton Colmenares
clinton.colmenares@vanderbilt.edu
615-322-4747
Vanderbilt University Medical Center
10-Feb-2003


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