Early in mammal development, tiny vesicles provide key communication between the cells that will become the fetus and those destined to form the placenta, researchers have found. The message the microvesicles are imparting: It’s time to implant into the wall of the uterus. While scientists already knew that maternal tissues promote implantation, sometimes via small vesicles, this is the first description of vesicle-mediated communication between the cells that will form the fetus and the proto-placenta, say the authors at Cornell University in Ithaca, New York. They hope the finding might lead to a treatment for infertility.

The study also shores up evidence that vesicle communication, oft-studied in cancer and other pathological conditions, contribute to normal biological processes in healthy people. Such vesicles are “an exploding area of research,” says Lois Salamonsen, a reproductive biologist at the Hudson Institute of Medical Research in Melbourne, Australia. “This is a really important first paper opening up this area of within-the-blastocyst communication,” adds Salamonsen, who was not involved in the study. The findings appear in the June 15 Nature Communications.

Cells release diverse vesicles to communicate with other cells, usually categorized as either exosomes of fewer than 100 nanometers in diameter, or microvesicles that range from 200 nanometers to two microns across, explains study author Rick Cerione. His co-senior author, Marc Antonyak, has studied the little packages in the context of cancer, and the pair wondered if embryonic stem cells might also release vesicles that performed biological functions. They found microvesicles and a role for them in the blastocyst, an embryonic stage about a week or so after egg fertilization but before implantation. It contains an inner cell mass that will become the fetus, plus a large fluid-filled cavity; these are surrounded by a layer of cells called trophoblasts that will implant in the uterine wall and generate the placenta.

The researchers purified microvesicles generated by mouse embryonic stem cells, then applied them to a human trophoblast cell line. In response, the cells started to spread out and travel in the dish, as if they were trying to implant in the uterus. They were more than twice as likely to do so as cells not exposed to the extra microvesicles. Two molecules on the vesicles’ surfaces, laminin and fibronectin, were crucial to induce the trophoblasts to travel. Other vesicle cargoes probably also contribute to the process, Cerione says.

Then the scientists collected blastocysts from mice and injected them with extra microvesicles, before surgically placing them into the uteri of surrogate mice mothers. These blastocysts achieved a rate of about 80% implantation, compared to only 60% for blastocysts that underwent no such special treatment.

Difficulties with implantation is a key cause of human infertility, and a common reason for failure of in-vitro fertilization (IVF), so the scientists suggest their work could lead to a treatment that would boost IVF pregnancy rates. Cerione speculates that it might also be possible to interfere with the signals provided by the vesicles and create a new form of birth control. But researchers still need to confirm that vesicles provide the same communication during a human pregnancy.