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Lack of stem cells in womb linked to miscarriage

Finding could herald new treatments

Jo Carlowe

Tuesday, 08 March 2016

A lack of stem cells in the womb lining is causing thousands of women to suffer from recurrent miscarriages.

Professor of Obstetrics & Gynaecology, Jan Brosens, at the University of Warwick, who led the breakthrough research, said: "We have discovered that the lining of the womb in the recurrent miscarriage patients we studied is already defective before pregnancy.”

He added: "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.”

The team, whose research* is published in the journal Stem Cells, 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.

The study, a collaboration between the University's Warwick Medical School and Warwick Systems Biology Centre, saw the researchers examine 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.

The team found that an epigenetic signature was absent in cultures established from womb biopsies taken from women suffering recurrent miscarriages. Indeed, fewer stem cells could be isolated from the lining of the womb from recurrent miscarriage patients when compared to women in the study's control group.

The researchers further found that a stem cell shortage accelerates cellular ageing in the womb. Ageing cells mount an inflammatory response, which may facilitate implantation of an embryo but is detrimental for its further development.

Professor Brosens added: "After an embryo has implanted, the lining of the uterus develops into a specialised structure called the decidua, and this process can be replicated when cells from the uterus are cultured in the lab.

"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.”

Co-author of the study, Siobhan Quenby, said: "The real challenge now is to develop strategies to increase the function of stem cells in the womb lining.

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.”

* Lucas ES, et al. Loss of Endometrial Plasticity in Recurrent Pregnancy Loss. Stem Cells, Volume 34, Issue 2, pages 346–356, February 2016. DOI: 10.1002/stem.2222

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