A study in mice suggests that bone marrow-derived stem cells may play a role in establishing pregnancy.
The research showed that the stem cells can travel through blood circulation to the uterus, making it more receptive for a new embryo. Specifically, the authors showed that these cells concentrate in the lining of the uterus where the embryo is about to implant. There, they become specialised uterine cells or decidual cells, which are critical for maintaining the embryo.
'We have always known that two kind of things were necessary for pregnancy: you must have ovaries to make eggs, and you must also have a uterus to receive the embryo,' said senior author, Dr Hugh Taylor at Yale University in New Haven, Connecticut. 'But knowing that bone marrow has a significant role is a paradigm shift.'
Previous studies had shown that small numbers of bone-marrow stem cells contribute to the renewal of the lining of the non-pregnant uterus, but it remained unknown whether they play a part in pregnancy.
This study is the first to show a physiological role for bone-marrow stem cells in pregnancy.
This work was possible due to a methodological breakthrough. Dr Taylor and his team at Yale were able to develop a mild chemotherapy for their mouse model that 'wiped out' the bone marrow of these mice without affecting their eggs, and therefore their fertility. Then they fertilised these mice before and after healthy bone-marrow transplantation to investigate whether the bone-marrow stem cells contributed to the establishment of pregnancy.
The team also used mice that lack a protein called Hoxa11, usually expressed in both uterine and bone marrow progenitor cells - mice without this protein have a deficient womb and cannot become pregnant. Mice that only partially lack Hoxa11 can become pregnant, but they experience recurrent miscarriages. When these mice received bone marrow transplants from healthy mice, both sets were able to become pregnant. The partially-deficient mice went ahead to have as many pregnancies as their healthy mice.
Several studies have implicated Hoxa11 production and conditions that relate in pregnancy failure, such as endometriosis. The authors suggest further investigations for the role of Hoxa11 and bone-marrow stem cells in the human pregnancy and its establishment.
'We are currently translating these findings into humans to better understand the role that these bone marrow-derived stem cells play in recurrent implantation failure and recurrent pregnancy loss, two conditions that are unexplained in the majority of women and have no effective treatment,' said Dr Reshef Tal, study first author.
'The findings of this study open exciting new avenues for research into the cause of these conditions as well as developing new treatments for women suffering from them.'
The research was published in PLOS Biology.