Researchers discover faulty molecular switch that cause infertility, miscarriage
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 contraceptives. 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 womb 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 Developmental Biology (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 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."
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
Provided by Imperial College London
- Rictor protein offers scientists a new molecular target for cancer therapies Oct 28, 2010 | not rated yet | 0
- Scientists identify possible cause of endometriosis Aug 05, 2008 | not rated yet | 0
- Removal of fibroids that distort the womb cavity may prevent recurrent miscarriages Sep 28, 2011 | not rated yet | 0
- Miscarriage and infertility treatment increase pre-eclampsia risk Dec 18, 2008 | not rated yet | 0
- Researcher finds caffeine consumption, female infertility link Jul 20, 2011 | not rated yet | 0
- Motion perception revisited: High Phi effect challenges established motion perception assumptions Apr 23, 2013 | 3 / 5 (2) | 2
- Anything you can do I can do better: Neuromolecular foundations of the superiority illusion (Update) Apr 02, 2013 | 4.5 / 5 (11) | 5
- The visual system as economist: Neural resource allocation in visual adaptation Mar 30, 2013 | 5 / 5 (2) | 9
- Separate lives: Neuronal and organismal lifespans decoupled Mar 27, 2013 | 4.9 / 5 (8) | 0
- Sizing things up: The evolutionary neurobiology of scale invariance Feb 28, 2013 | 4.8 / 5 (10) | 14
Why is zone 1 in liver more prone to ischemic injury?
May 23, 2013 Hi, Is it because around central vein, there is only deoxygenated blood from the vein where as in the periphery there is hepatic artery. Also why...
How can there be villous adenoma in colon, if there are no villi there
May 22, 2013 As title suggest. Thanks :smile:
How can there be a term called "intestinal metaplasia" of stomach
May 21, 2013 Hello everyone, Ok Stomach's normal epithelium is simple columnar, now in intestinal type of adenocarcinoma of stomach it undergoes "intestinal...
Pressure-volume curve: Elastic Recoil Pressure don't make sense
May 18, 2013 From pressure-volume curve of the lung and chest wall (attached photo), I don't understand why would the elastic recoil pressure of the lung is...
If you became brain-dead, would you want them to pull the plug?
May 17, 2013 I'd want the rest of me to stay alive. Sure it's a lousy way to live but it beats being all-the-way dead. Maybe if I make it 20 years they'll...
MRI bill question
May 15, 2013 Dear PFers, The hospital gave us a $12k bill for one MRI (head with contrast). The people I talked to at the hospital tell me that they do not...
- More from Physics Forums - Medical Sciences
More news stories
By discovering the new mechanism by which estrogen suppresses lipid synthesis in the liver, UC Irvine endocrinologists have revealed a potential new approach toward treating certain liver diseases.
Medical research 22 hours ago | not rated yet | 0 |
Aortic arch pulse wave velocity, a measure of arterial stiffness, is a strong independent predictor of disease of the vessels that supply blood to the brain, according to a new study published in the June issue the journal ...
Medical research 22 hours ago | not rated yet | 0
Since the discovery of Prontosil in 1932, sulfonamide antibiotics have been used to combat a wide spectrum of bacterial infections, from acne to chlamydia and pneumonia. However, their side effects can include serious neurological ...
Medical research 23 hours ago | not rated yet | 0 |
Scientists at the National Institutes of Health report they have discovered in mouse studies that a small molecule released in the spinal cord triggers a process that is later experienced in the brain as ...
Medical research 23 hours ago | 5 / 5 (3) | 0 |
Spanish researchers have discovered that the daily clearance of neutrophils from the body stimulates the release of hematopoietic stem cells from the bone marrow into the bloodstream, according to a report published today ...
Medical research May 23, 2013 | 5 / 5 (2) | 0
(HealthDay)—We've all seen them: the surfers who race to the beach when a hurricane hits, the guy who decides to ride out the storm in his overmatched boat, the tornado chasers who fearlessly steer their ...
56 minutes ago | not rated yet | 0
(HealthDay)—New evidence-based guidelines provide guidance on medical and surgical methods for second-trimester abortion and management of associated complications, according to a practice bulletin published ...
36 minutes ago | not rated yet | 0
(HealthDay)—More than one in four of those eligible for new premium assistance tax credits under the Affordable Care Act (ACA) do not have a checking account and will not be able to receive premiums from ...
26 minutes ago | not rated yet | 0
(HealthDay)—Comorbid conditions often accompany alopecia areata, according to a study published online May 22 in JAMA Dermatology.
6 minutes ago | not rated yet | 0
(HealthDay)—As a world-class golfer, Stacy Lewis' accomplishments are remarkable. But it was a physical challenge in her childhood that defined her ascent to the top of her sport.
46 minutes ago | not rated yet | 0
Women at a particular stage in their monthly menstrual cycle may be more vulnerable to some of the psychological side-effects associated with stressful experiences, according to a study from UCL.
1 hour ago | not rated yet | 0 |