Lack of stem cells in womb lining may be the cause of recurrent miscarriages

Written by Elena Conroy

Researchers from the University of Warwick are now looking into a treatment, giving hope to women who have suffered from reproductive failure.

A collaborative study between the University’s Warwick Medical School and Warwick Systems Biology Centre (Warwick, UK) discovered that a lack of stem cells in the womb lining may be the cause of recurrent miscarriages in thousands of women. The team behind this breakthrough is now looking into a treatment that could bring hope to those who have suffered failed pregnancies. The findings were recently published in Stem Cells.

Miscarriage is the most common cause of loss. Between 15-25% of pregnancies end in miscarriage and one in 100 women trying to conceive suffer recurrent miscarriages, which is defined as the loss of three or more consecutive pregnancies.

The research team found a shortfall of stem cells is the likely cause of accelerated ageing of the lining of the womb which results in the failure of some pregnancies.

“We have discovered that the lining of the womb in the recurrent miscarriage patients we studied is already defective before pregnancy,” commented Jan Brosens, team leader and Professor of Obstetrics & Gynecology at Warwick Medical School at the University of Warwick. “I can envisage that we will be able to correct these defects before the patient tries to achieve another pregnancy. In fact, this may be the only way to really prevent miscarriages in these cases.”

Tissue samples from the womb lining, donated by 183 women who were being treated at the Implantation Research Clinic, University Hospitals Coventry and Warwickshire NHS Trust were examined.

The team discovered that a typical epigenetic signature is stem cells was absent in cultures established from womb biopsies taken from the women suffering recurrent miscarriages. The findings demonstrated that fewer stem cells could be isolated from the lining of the womb from recurrent miscarriage patients compared to women in the study’s control group.

The researchers further found that a stem cell shortage accelerates cellular ageing in the womb. The lining has to renew itself each cycle, each miscarriage and successful birth, which is dependent on the resident stem cell population. A shortage of these stem cells in patients suffering recurrent loss is associated with accelerated ageing of the tissue. Ageing cells mount an inflammatory response, which may facilitate implantation of an embryo but is detrimental for its further development.

“After an embryo has implanted, the lining of the uterus develops into a specialized structure called the decidua, and this process can be replicated when cells from the uterus are cultured in the lab” added Brosens. “Cultured cells from women who had had three or more consecutive miscarriages showed that ageing cells in the lining of the womb don’t have the ability to prepare adequately for pregnancy.”

“The real challenge now is to develop strategies to increase the function of stem cells in the womb lining,” explained Siobhan Quenby, co-author of the study and professor of Obstetrics at the University. “We will start piloting new interventions to improve the lining of the womb in the spring of 2016. Our focus will be two-fold. First, we wish to improve the screening of women at risk of recurrent miscarriage by developing new endometrial tests. Second, there are a number of drugs and other interventions, such as endometrial ‘scratch’, a procedure used to help embryos implant more successfully, that have the potential to increase the stem cell populations in the womb lining.”

The University of Warwick has now been selected to be a partner in the largest miscarriage research center in Europe which will be opening next month. Funded by Tommy’s, the leading pregnancy charity, the University’s researchers will be joining doctors from University Hospital, Coventry (UK) to investigate the causes of early miscarriage.


Lucas ES, Dyer NP, Murakami K et al. Loss of Endometrial Plasticity in Recurrent Pregnancy Loss. Stem Cells, doi: 10.1002/stem.2222 (2016) (Online before print);