Nav: Home

Bone marrow may be the missing piece of the fertility puzzle

September 12, 2019

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

"We have always known that two kind of things were necessary for pregnancy," says Dr. Hugh Taylor, senior author and the Anita O'Keeffe Young Professor of Obstetrics, Gynecology, and Reproductive Sciences at Yale. "You must have ovaries to make eggs, and you must also have a uterus to receive the embryo. But knowing that bone marrow has a significant role is a paradigm shift."

Previous research has indicated that, in small numbers, bone marrow-derived stem cells contribute to the non-immune environment of the non-pregnant uterus, but it's remained unknown if and how stem cells affect a pregnant uterus. In this study, the researchers were able to prove the physiological relevance of stem cells to pregnancy.

"Some of these bone marrow-derived mesenchymal stem cells travel to the uterus and become decidual cells, which are the cells that are essential for the process of implantation and pregnancy maintenance," explains Dr. Reshef Tal, first author of the study and assistant professor of obstetrics, gynecology and reproductive sciences at Yale.

In two mouse models with the Hoxa11 gene defect, which presents 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 only one copy of the defective gene, the transplant saved pregnancies that would otherwise have been lost and increased litter sizes, while in the mice with two bad copies of the gene, which were thus entirely infertile, the transplant caused growth and repair of the defective endometria.

This study was made possible by a methods breakthrough that Tal and Taylor made a few years ago. For more than two decades, Taylor and his team had been trying to restore fertility in mice with these genetic mutations, but until recently, they didn't have a form of chemotherapy strong enough to allow an effective bone marrow transplant without killing all the eggs of the mice. (Before a bone marrow transplant, chemotherapy or radiation is used to clear the body of the existing bone marrow, so that the donor bone marrow can take its place.)

"We used an anti-metabolite drug, which is still considered a chemotherapy, but it doesn't harm the ovary, and therefore the mice are still able to get pregnant, allowing us to track the transplanted bone marrow cells and investigate their role in reproduction," says Tal. "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."

Though more research is needed prior to clinical trials, Tal and Taylor see hope for the patients they treat for infertility on the clinical side of their practice in this latest advance.

"These are frustrating medical conditions," says Taylor. "When you have a damaged endometrium leading to infertility or repeated pregnancy loss, all too frequently we have not been able to correct it. Bone marrow can be considered another critical reproductive organ. This finding opens up a new potential avenue for treatment of a condition that has been untreatable in the past."
-end-
Other authors on the study include Shafiq Shaikh, Pallavi Pallavi, Aya Tal, Francesc López-Giráldez, Fang Lyu, Yuan-Yuan Fang, Shruti Chinchanikar, Ying Liu, Harvey J. Kliman, Myles Alderman, III, Nicola Pluchino, Jehanzeb Kayani, Ramanaiah Mamillapalli, and Diane S. Krause.

The study was funded by the National Institutes of Health, the Ferring/New England Fertility Society, the American Society for Reproductive Medicine, and the Robert E. Leet and Clara Guthrie Patterson Fellowship.

Yale University

Related Stem Cells Articles:

More selective elimination of leukemia stem cells and blood stem cells
Hematopoietic stem cells from a healthy donor can help patients suffering from acute leukemia.
Computer simulations visualize how DNA is recognized to convert cells into stem cells
Researchers of the Hubrecht Institute (KNAW - The Netherlands) and the Max Planck Institute in Münster (Germany) have revealed how an essential protein helps to activate genomic DNA during the conversion of regular adult human cells into stem cells.
First events in stem cells becoming specialized cells needed for organ development
Cell biologists at the University of Toronto shed light on the very first step stem cells go through to turn into the specialized cells that make up organs.
Surprising research result: All immature cells can develop into stem cells
New sensational study conducted at the University of Copenhagen disproves traditional knowledge of stem cell development.
The development of brain stem cells into new nerve cells and why this can lead to cancer
Stem cells are true Jacks-of-all-trades of our bodies, as they can turn into the many different cell types of all organs.
Healthy blood stem cells have as many DNA mutations as leukemic cells
Researchers from the Princess Máxima Center for Pediatric Oncology have shown that the number of mutations in healthy and leukemic blood stem cells does not differ.
New method grows brain cells from stem cells quickly and efficiently
Researchers at Lund University in Sweden have developed a faster method to generate functional brain cells, called astrocytes, from embryonic stem cells.
NUS researchers confine mature cells to turn them into stem cells
Recent research led by Professor G.V. Shivashankar of the Mechanobiology Institute at the National University of Singapore and the FIRC Institute of Molecular Oncology in Italy, has revealed that mature cells can be reprogrammed into re-deployable stem cells without direct genetic modification -- by confining them to a defined geometric space for an extended period of time.
Researchers develop a new method for turning skin cells into pluripotent stem cells
Researchers at the University of Helsinki, Finland, and Karolinska Institutet, Sweden, have for the first time succeeded in converting human skin cells into pluripotent stem cells by activating the cell's own genes.
In mice, stem cells seem to work in fighting obesity! What about stem cells in humans?
This release aims to summarize the available literature in regard to the effect of Mesenchymal Stem Cells transplantation on obesity and related comorbidities from the animal model.
More Stem Cells News and Stem Cells Current Events

Trending Science News

Current Coronavirus (COVID-19) News

Top Science Podcasts

We have hand picked the top science podcasts of 2020.
Now Playing: TED Radio Hour

Making Amends
What makes a true apology? What does it mean to make amends for past mistakes? This hour, TED speakers explore how repairing the wrongs of the past is the first step toward healing for the future. Guests include historian and preservationist Brent Leggs, law professor Martha Minow, librarian Dawn Wacek, and playwright V (formerly Eve Ensler).
Now Playing: Science for the People

#565 The Great Wide Indoors
We're all spending a bit more time indoors this summer than we probably figured. But did you ever stop to think about why the places we live and work as designed the way they are? And how they could be designed better? We're talking with Emily Anthes about her new book "The Great Indoors: The Surprising Science of how Buildings Shape our Behavior, Health and Happiness".
Now Playing: Radiolab

The Third. A TED Talk.
Jad gives a TED talk about his life as a journalist and how Radiolab has evolved over the years. Here's how TED described it:How do you end a story? Host of Radiolab Jad Abumrad tells how his search for an answer led him home to the mountains of Tennessee, where he met an unexpected teacher: Dolly Parton.Jad Nicholas Abumrad is a Lebanese-American radio host, composer and producer. He is the founder of the syndicated public radio program Radiolab, which is broadcast on over 600 radio stations nationwide and is downloaded more than 120 million times a year as a podcast. He also created More Perfect, a podcast that tells the stories behind the Supreme Court's most famous decisions. And most recently, Dolly Parton's America, a nine-episode podcast exploring the life and times of the iconic country music star. Abumrad has received three Peabody Awards and was named a MacArthur Fellow in 2011.