Deregulation of a protein kinase involved in fluid balance in the body is linked to two different forms of reproductive failure in humans, as reported this week in Nature Medicine. As kinases can be targeted by drugs, it is possible that these insights may some day allow for pharmacological prevention of these conditions.
Women often suffer from infertility or recurrent pregnancy loss. While these are distinct instances of reproductive failure, Jan Brosens and his colleagues have shown that dysregulated expression of a single kinase, SGK1, in two different cellular compartments of the endometrium — the uterus lining — is linked to these pathologies. They found that SGK1 expression is higher in the luminal epithelia of the endometrium in women who suffer unexplained infertility, while it is lower in the endometrial stroma from women who have suffered recurrent pregnancy loss.
The mechanisms linking altered SGK1 expression to these reproductive outcomes appear different. Brosens found that increased SGK1 activity in endometrial surface epithelium selectively disrupts the expression of implantation genes and perturbs the local fluid environment, leading to infertility. Reduced endometrial SGK1 activity during pregnancy, however, leads to a failure to protect against oxidative stress signals generated by the intense tissue remodelling that occurs, thus resulting in fetal loss.