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Link Discovered Between an Enzyme and Infertility, Miscarriage
British researchers have discovered a link between an enzyme and infertility and miscarriage. Enzymes are proteins that increase the rates of chemical reactions. This enzyme, called SGK1, acts as a type of "fertility switch," with high levels linked to infertility and low levels linked to miscarriage.
The study, published in Nature Medicine, examined tissue samples from the uterine lining, which were donated by 106 women who were being treated at Imperial College Healthcare NHS Trust either for unexplained infertility or for recurrent pregnancy loss. The women with unexplained infertility had been trying to get pregnant for two years or more, with the common reasons for infertility being ruled out. Researchers found that the uterine lining in these women had high levels of the enzyme SGK1.
The researchers found more information from experiments with mice. Levels of SGK1 in the womb lining decline during the fertile window in mice. When the researchers implanted extra copies of the SGK1 gene into the womb lining, the mice were unable to get pregnant. This suggests that a fall in SGK1 levels is essential for making the uterus receptive to embryos.
"Our experiments on mice suggest that a temporary loss of SGK1 during the fertile window is essential for pregnancy, but human tissue samples show that they remain high in some women who have trouble getting pregnant," said lead researcher Jan Brosens, who is now based at the University of Warwick. "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."
The researchers found that women suffering from recurrent pregnancy loss — defined as the loss of three or more consecutive pregnancies — had low levels of SGK1. After an embryo is implanted, the lining of the uterus develops into a specialized structure called the decidua — a process that can be recreated artificially 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.
"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 of the 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."