Thousands of women have multiple pregnancies that end in miscarriage. Now, researchers have found that recurrent miscarriages may be caused by a lack of stem cells in the womb lining, called the endometrium. The findings, published in the journal Stem Cells, could lead to treatments that will increase stem cell functions for women who are at risk.
As many as 25 percent of pregnancies are lost before the fetus is viable. Most miscarriages are sporadic and occur before 12 weeks of gestation, but recurrent pregnancy loss – defined by consecutive miscarriages – is a distinct disorder. It’s estimated that 5 percent of women experience two miscarriages, and about 1 percent endure three or more losses. While many risk factors have previously been linked to recurrent pregnancy loss, the underlying pathological pathways weren't understood.
To investigate, University of Warwick’s Jan Brosens and colleagues cultured cells isolated from tissue samples that came from the endometrium of 183 women. They focused on a particular signature of stem cells, which was absent from womb biopsies taken from women who have had recurrent miscarriages. As a result, the team wasn’t able to isolate as many stem cells from the endomentrium of these women compared to those in the control group.
Furthermore, this shortfall accelerates the cellular aging in the womb lining – making it incapable of preparing adequately for pregnancy. The endometrium renews itself during each menstrual cycle and each miscarriage or successful birth, and this ability for renewal depends on the resident stem cell population. While aging cells may mount an inflammatory response that helps with embryo implantation, this action is harmful for the development of the embryo later on.
“We have discovered that the lining of the womb in the recurrent miscarriage patients we studied is already defective before pregnancy,” Brosens says in a statement. “I can envisage that we will be able to correct these defects before the patient tries to achieve another pregnancy.”