A common diabetes drug can help women with repeated miscarriages, researchers found after discovering that a certain type of stem cell deficiency is common in women who lose pregnancies.
A study for Tommy’s National Miscarriage Research Center in London found that the diabetes drug sitagliptin can help recruit these cells into the lining of the uterus, called the endometrium, in women with recurrent miscarriages.
The drug also reduced the number of stressed “senescent” cells – those that no longer divide but are also resistant to death – which can be linked to an increased risk of spontaneous premature births.
However, the study wasn’t big enough to see if the drug lowered the miscarriage rate. Jan Brosens, professor of obstetrics and gynecology at the University of Warwick and scientific director of Tommy, hopes to start a larger study next year with funding.
Miscarriages are the most common complication of pregnancy and are estimated to affect one in four pregnancies. The quality of the eggs is an important factor as women release a greater proportion of chromosomally abnormal eggs as they age. Another important factor, however, is the quality of the endometrium to which the fertilized egg attaches.
During the second half of the menstrual cycle, the endometrium turns into tissue that could feed a growing embryo. If fertilization does not take place, this will be shed during menstruation. “Women can have normal cycles in which the lining of the uterus is converted into tissue that can be maintained in pregnancy for nine months, or they can have abnormal cycles in which this transition fails and ultimately the entire interface with the placenta breaks down early in pregnancy which leads to miscarriages, ”said Brosens.
Previous studies had shown that this remodeling was due to the presence of a discrete population of stem cells called highly proliferative mesenchymal cells (hPMC), and that they tend to be depleted in women with repeated miscarriages. What was not known is where they are from and what exactly they are doing.
Now, Brosens and colleagues have characterized these cells in more detail and found that they almost certainly come from stem cells in the bone marrow that 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 found that they land at the interface between the placenta and the lining of the uterus.
Brosens said, “These cells appear to be critical during pregnancy to accommodate the rapidly growing placenta. We also found that they are depleted in the lining of the uterus in women with recurrent pregnancy loss. I think the main problem is that the lining of the uterus doesn’t generate the right signals every cycle to recruit these cells in sufficient quantities. “
Dr. Jan Nolta, Director of the Stem Cell Program at the University of California at Davis and Editor-in-Chief of Stem Cells, who published the study, said, “This key study begins to provide answers to a very worrisome problem in pregnancy and provides insight into the understanding of disorders Factors That Can Contribute To Pregnancy Loss. “