Researchers discover faulty molecular switch that cause infertility, miscarriage

October 16, 2011, Imperial College London

Scientists have discovered an enzyme that acts as a 'fertility switch', in a study published in Nature Medicine today. High levels of the protein are associated with infertility, while low levels make a woman more likely to have a miscarriage, the research has shown.

The findings have implications for the treatment of infertility and recurrent miscarriage and could also lead to new . Around one in six women have difficulty getting pregnant and one in 100 women trying to conceive have recurrent miscarriages, defined as the loss of three or more consecutive pregnancies.

Researchers from Imperial College London looked at tissue samples from the lining, 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 and the most common reasons for infertility had been ruled out. The researchers discovered that the womb lining in these women had high levels of the enzyme SGK1. Conversely, the women suffering from recurrent pregnancy loss had low levels of SGK1.

The team found further evidence of SGK1's importance in experiments using mouse models. 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, suggesting that a fall in SGK1 levels is essential for making the uterus receptive to embryos.

The research at the Institute of Reproductive and (IRDB) at Imperial College London was led by Professor Jan Brosens, who is now based at the University of Warwick. "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," 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 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 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 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."

Explore further: Removal of fibroids that distort the womb cavity may prevent recurrent miscarriages

More information: Salker MS, Christian M, Steel JH, Nautiyal J, Lavery S, Trew G, Webster Z, Al-Sabbagh M, Puchchakayala G, Föller M, Landles C, Sharkey AM, Quenby S, Aplin JD, Regan L, Lang F and Brosens JJ, "Deregulation of the serum- and glucocorticoid-inducible kinase SGK1 in the endometrium causes reproductive failure," Advance Online Publication (AOP) in Nature Medicine, October 16, 2011. DOI:10.1038/nm.2498

Related Stories

Removal of fibroids that distort the womb cavity may prevent recurrent miscarriages

September 28, 2011
Researchers have found the first, firm evidence that fibroids are associated with recurrent miscarriages. They have also discovered that if they removed the fibroids that distorted the inside of the womb, the risk of miscarriage ...

Researcher finds caffeine consumption, female infertility link

July 20, 2011
Caffeine reduces muscle activity in the Fallopian tubes that carry eggs from a woman's ovaries to her womb. "Our experiments were conducted in mice, but this finding goes a long way towards explaining why drinking caffeinated ...

Recommended for you

Researchers devise decoy molecule to block pain where it starts

January 16, 2018
For anyone who has accidentally injured themselves, Dr. Zachary Campbell not only sympathizes, he's developing new ways to blunt pain.

Scientists unleash power of genetic data to identify disease risk

January 16, 2018
Massive banks of genetic information are being harnessed to shed new light on modifiable health risks that underlie common diseases.

Blood-vessel-on-a-chip provides insight into new anti-inflammatory drug candidate

January 15, 2018
One of the most important and fraught processes in the human body is inflammation. Inflammatory responses to injury or disease are crucial for recruiting the immune system to help the body heal, but inflammation can also ...

Molecule produced by fat cells reduces obesity and diabetes in mice

January 15, 2018
UC San Francisco researchers have discovered a new biological pathway in fat cells that could explain why some people with obesity are at high risk for metabolic diseases such as type 2 diabetes. The new findings—demonstrated ...

Obese fat becomes inflamed and scarred, which may make weight loss harder

January 12, 2018
The fat of obese people becomes distressed, scarred and inflamed, which can make weight loss more difficult, research at the University of Exeter has found.

Optimized human peptide found to be an effective antibacterial agent

January 11, 2018
A team of researchers in the Netherlands has developed an effective antibacterial ointment based on an optimized human peptide. In their paper published in the journal Science Translational Medicine, the group describes developing ...

0 comments

Please sign in to add a comment. Registration is free, and takes less than a minute. Read more

Click here to reset your password.
Sign in to get notified via email when new comments are made.