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Faulty molecular switch can cause infertility or miscarriage

Date:10/16/2011

getting pregnant," he said. "I can envisage that in the future, we might treat the womb lining by flushing it with drugs that block SGK1 before women undergo IVF. Another potential application is that increasing SGK1 levels might be used as a new method of contraception."

Any infertility treatment that blocks SGK1 would have to have a short-lived effect, as low levels of the protein after conception seem to be linked to miscarriage. When the researchers blocked the gene that codes for SGK1 in mice, the mice had no problem getting pregnant. However, they had smaller litters and showed signs of bleeding in the uterus, suggesting that lack of SGK1 made miscarriage more likely.

After an embryo is implanted, the lining of the uterus develops into a specialised structure called the decidua, and this process can be made to occur when cells from the uterus are cultured in the lab. Cultured cells from women who had had three or more consecutive miscarriages had significantly lower levels of SGK1 compared to cells from controls.

Blocking the SGK1 gene, both in pregnant mice and in human cell cultures, impaired the cells' ability to protect themselves against oxidative stress, a condition in which there is an excess of reactive chemicals inside cells.

"We found that low levels of SGK1 make the womb lining vulnerable to cellular stress, which might explain why low SGK1 was more common in women who have had recurrent miscarriage," said Madhuri Salker, the study's first author, Institute of Reproductive and Developmental Biology (IRDB) at Imperial College London. "In the future, we might take biopsies of the womb lining to identify abnormalities that might give them a higher risk of pregnancy complications, so that we can start treating them before they get pregnant."

Contact: Simon Levey
s.levey@imperial.ac.uk
44-020-759-46702
Imperial College London
Source:Eurekalert

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