Bone marrow can be the missing piece of the fertility puzzle

A woman's bone marrow can determine her ability to initiate and maintain a pregnancy, report Yale researchers in PLOS Biology. The study shows that when an egg is fertilized, the stem cells leave the bone marrow and go to the uterus through the bloodstream, where they help to transform the uterine lining for implantation. . If the mucosa fails to perform this essential transformation, the embryo can not implant and the body terminates the pregnancy.

"We always knew that two types of things were needed for pregnancy," says Dr. Hugh Taylor, lead author and professor Anita O. Keeffe Young in Obstetrics, Gynecology and Reproductive Sciences at Yale. "You must have ovaries to make eggs and a uterus to receive the embryo, but knowing that bone marrow has an important role to play is a paradigm shift."

Previous research has shown that, in small numbers, stem cells derived from the bone marrow contribute to the non-immune environment of the non-pregnant uterus, but it is unclear whether and how stem cells affect the uterus. pregnant uterus. In this study, researchers were able to prove the physiological relevance of stem cells for pregnancy.

"Some of these mesenchymal stem cells derived from the bone marrow move into the uterus and become decidual cells, essential cells for the process of implantation and maintenance of pregnancy," says Dr. Reshef Tal, first author of the study and assistant. Professor of Obstetrics, Gynecology and Reproductive Sciences at Yale.

In two murine models with an abnormality of the Hoxa11 gene, which occurs in mice as a defective endometrium, the researchers found that a bone marrow transplant from a healthy donor could improve fertility by promoting sufficient decidualization of the endometrium. In mice with a single copy of the defective gene, the graft saved pregnancies that would otherwise have been lost and increased litter size, whereas in mice with two bad copies of the gene, which were therefore completely sterile, the graft was caused growth and repair. defective endometrium.

This study was made possible thanks to a discovery of methods that Tal and Taylor did a few years ago. For more than two decades, Taylor and his team have been trying to restore fertility in mice with these genetic mutations, but until recently, they did not have a form of chemotherapy powerful enough to allow for a transplantation. effective bone marrow without killing all the eggs. mouses. (Before a bone marrow transplant, chemotherapy or radiation therapy is used to clean the body of the existing bone marrow, so that the donor's bone marrow can take its place.)

"We used an anti-metabolite drug, which is still considered chemotherapy, but it does not harm the ovary, so the mice are still able to get pregnant, which allows us to track the cells. transplanted bone marrow and investigate their reproductive role, "Tal says. "We are currently translating these results into humans to better understand the role that these bone marrow-derived stem cells play in recurrent implantation failures and recurrent pregnancy loss, two conditions unexplained in the majority women and not benefiting from any effective treatment. "

Although more research is needed before clinical trials, Tal and Taylor hope that the patients they treat for infertility will have an increasingly clinical role in their practice.

"These are frustrating medical conditions," says Taylor. "When your endometrium is damaged, resulting in infertility or repeated pregnancy loss, we have often failed to correct it." Bone marrow may be considered another essential organ of reproduction. potential route for the treatment of a condition that has been incurable in the past ".