Faulty switch causes fertility problems
19 Dec 2011 by Evoluted New Media
Infertility and miscarriage can be caused by a faulty molecular switch which controls the level of a protein in the womb lining say researchers at Imperial College London. Researchers studied womb lining tissue samples donated by 106 women who were being treated at Imperial College Healthcare NHS Trust for unexplained infertility or recurrent pregnancy loss (RPL). They discovered SGK1 – a kinase involved in epithelial ion transport and cell survival – was responsible for both.
In women with unexplained infertility, researchers discovered the enzyme is upregulated – the women had high levels of SGK1 in their womb lining, particularly in the luminal epithelium. Conversely, it is downregulated in women suffering from RPL – the loss of three or more consecutive pregnancies.
“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, first author of the study published in Nature Medicine.
Experiments using mouse models showed SGK1 levels in the womb lining decline during the fertile window. When researchers expressed a constitutively active SGK1 mutant in the luminal epithelium, it prevented the expression of certain endometrial receptivity genes, perturbed uterine fluid handling and abolished embryo implantation. This suggests the fall in SGK1 levels is essential for making the uterus receptive to embryos.
“Our experiments on mice suggest that the 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 Professor Jan Brosens, who led the research.
When researchers blocked the gene that codes for SGK1 in mice, the mice had no problem getting pregnant, but the pregnancy was complicated by bleeding at the decidual-placental interface, foetal growth retardation and miscarriage.
“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,” said Brosens. “Another application is that increasing SGK1 levels might be used as a new method of contraception.
Salker believes that doctors may be able to take a biopsy of the womb lining to identify abnormalities that might cause a higher risk of pregnancy complications, which can then be treated before a woman conceives.
