Fertility study shows increased estrogen shortens window of implantation in mice

VANDERBILT One of the most vexing causes of infertility is the failure of the embryo to implant in the uterus. It's estimated that roughly three-quarters of all embryos fail to implant properly. And in those women being treated for infertility, even when healthy embryos are transplanted the failure rate is high: up to 70 percent fail to dock successfully in the uterine lining.

The interplay of signals between embryo and uterus during implantation is complex, yet recent findings by a group of Vanderbilt researchers may provide clues to better understand it. The group, led by S.K. Dey, Ph.D., Dorothy Overall Wells Professor of Pediatrics and Cell & Developmental Biology, has found evidence in mice suggesting that estrogen plays a critical role in determining the window of uterine receptivity for embryo implantation.

A report of the researchers' work, which could have implications for improving human fertility, currently appears in the online version of the journal Proceedings of the National Academy of Sciences, USA.

The studies show that too much estrogen alters expression of implantation-related genes in the uterus, which can rapidly abolish uterine receptivity to the embryo. Moreover, the amount of estrogen sufficient to elicit these changes is very small.

"The most exciting aspect of this investigation is that a very narrow range of estrogen levels can alter embryo implantation and gene expression," said Dey, who is also head of the division of Reproductive and Developmental Biology. "We're talking about nanogram levels here, which I would consider to be almost physiological doses in the mouse."

For their studies, the scientists allowed mice to copulate, then removed the ovaries of female mice to halt normal production of estrogen and progesterone, both of which are required for implantation to occur. Daily doses of progesterone kept the mice in a state of "delayed implantation," where any developing embryo, or blastocyst,

Contact: Clinton Colmenares
Vanderbilt University Medical Center

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