Getting Attached: Sugar-protein link joins embryo to Mom

It’s the first bond between a mother and her child–and arguably, the most vital one.

When a newly created human embryo enters its mother’s uterus, it must attach to the wall if it’s going to continue developing. The molecules that mediate this initial attachment may be the same ones that white blood cells use to leave the bloodstream and travel to a wound or infection, according to a study in the Jan. 17 Science. If confirmed, this discovery could explain some women’s infertility and lead to new contraceptives.

Reproduction is a matter of timing. After ovulation, a surge of hormones triggers temporary changes in the uterine wall that enable a human embryo to attach and implant itself. For years, researchers have studied this so-called window of uterine receptivity.

The new insight into the attachment process emerged from studies of embryos already implanted in the uterine wall. Susan J. Fisher of the University of California, San Francisco and her colleagues were examining human placenta, the tissue through which oxygen and nutrients flow from a mother to a developing fetus. The team discovered that the placental cells make L-selectin, a protein usually seen on white blood cells, such as neutrophils.

When these immune cells are called into action, L-selectin and related molecules bind to carbohydrates on the inside surface of a blood vessel. This positions the cells to migrate to injured tissues outside the vessel.

Intrigued by the discovery of placental L-selectin, Fisher wondered whether the protein had an even earlier presence in the embryo. The placenta derives from embryonic cells called trophoblasts, which form a ball around the cells that ultimately develop into the fetus. When Fisher and researchers at a fertility clinic examined unused human embryos donated for research, they found that human trophoblasts make L-selectin. “The cells make as much as a neutrophil,” she says.

The investigators then took tissue samples from the uterine walls of women at different stages of their menstrual cycle. The team discovered that during the window of receptivity, the wall’s inner surface begins to display several L-selectin-binding carbohydrates. Fisher and her colleagues also showed that an antibody to L-selectin inhibited lab-grown trophoblasts from binding to uterine tissue harvested during the window of receptivity.

Compounds that block L-selectin or its partners could offer a new form of female contraception, says Daniel Carson of the University of Delaware in Newark.

However, Susan J. Kimber of the University of Manchester in England cautions that Fisher’s group hasn’t directly shown that human embryos use L-selectin for their initial uterine attachment. Moreover, Kimber says, her research team has failed to find L-selectin on human embryos.

But if L-selectin is crucial to implantation, it may explain why some women with sexually transmitted diseases or other genital infections have trouble conceiving.

Infections can cause cells to shed L-selectin, which could hinder an embryo from attaching to the uterus, Fisher explains.


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