Diabetes drug may help women who have repeated miscarriages – study
A common diabetes drug may be able to help women who have repeated miscarriages, researchers have found, after they identified that a certain type of stem cell deficiency is common among women who lose pregnancies.
A study for the Tommy’s National Miscarriage Research Centre in London discovered that the diabetes drug sitagliptin can boost recruitment of these cells to the lining of the uterus, called the endometrium, in women who have experienced repeated miscarriages.
The drug also reduced the number of stressed “senescent” cells – ones that have ceased to divide but are also resistant to dying – which may be associated with an increased risk of spontaneous preterm labour.
However, the study wasn’t big enough to detect whether the drug reduced miscarriage rates. Jan Brosens, a professor of obstetrics and gynaecology at the University of Warwick and the scientific director of Tommy’s, hopes to launch a larger trial within the next year, subject to funding.
Miscarriages are the most common complication of pregnancy, affecting an estimated one in four pregnancies. Egg quality is a major factor, with women releasing a greater proportion of chromosomally abnormal eggs as they get older, but another important factor is the quality of the endometrium to which the fertilised egg attaches.
During the second half of the menstrual cycle, the endometrium remodels itself into a tissue that could nurture a growing embryo. If fertilisation doesn’t occur, this is what is shed during menstruation. “Women can have normal cycles where the lining of the womb is transformed into a tissue that can be maintained for nine months in pregnancy, or they can have abnormal cycles where this transition fails, and ultimately the whole interface with the placenta breaks down in early pregnancy, resulting in miscarriage,” said Brosens.
Previous studies had suggested that this remodelling is driven by the presence of a discrete population of stem cells called highly proliferative mesenchymal cells (hPMC), and that they tend to be depleted in women who have repeated miscarriages. What wasn’t known is where they come from and precisely what they’re doing.
Now Brosens and his colleagues have characterised these cells in more detail and discovered that they are almost certainly derived from stem cells in the bone marrow, which circulate in the blood and are actively recruited into the womb during the fertile part of a woman’s menstrual cycle. They also tracked what happens to these cells during pregnancy and discovered that they end up at the interface between the placenta and the lining of the womb.
Brosens said: “These cells appear
critical in pregnancy to accommodate the rapidly growing placenta. We also found that they are depleted in the womb lining of women with recurrent pregnancy loss. I think the primary problem is that the lining of the womb does not generate the right signals each cycle to recruit these cells in sufficient quantities.”
Dr Jan Nolta, the director of the stem cell programme at the University of California in Davis and editor-inchief of Stem Cells, which published the research, said:“This key study begins to find answers to a very concerning problem in pregnancy disorders and gives insight into understanding factors that could contribute to pregnancy loss.”