Fetal lungs tell mom when to deliver baby.

One of the central unresolved questions in mammalian biology is how a mother knows when to give birth. Scientists studying mice have now found evidence that the maturing lungs of a fetus release a protein that initiates the process.

If also true in women, the finding could provide insight into the causes of premature births and suggest ways of preventing them. About 6 to 10 percent of all pregnancies end with prematurely born babies, who frequently struggle to survive even with intensive medical care.

There's been a long debate among reproductive biologists about whether the fetus or the mother controls the timing of birth. The new research, led by Carole R. Mendelson of University of Texas Southwestern Medical Center in Dallas, suggests that the fetus is in charge.

This conclusion stems from studies of surfactant protein-A (SP-A), which in newborns appears to defend the lungs against microbes. Mendelson's colleague Jennifer C. Condon found that the concentration of SPA in the amniotic fluid around a mouse fetus rises sharply at the end of the rodent's 19-day gestation period. "It isn't there [in the fluid] until 2 days before birth and then, all of a sudden, it's there in high concentrations," says Mendelson.

Next, the investigators discovered that they could induce premature labor in mice within 24 hours by injecting SP-A into amniotic fluid. The researchers also found that injecting amniotic fluid with an antibody that blocks SP-A delays labor by 1 day in mice.

With another set of experiments, they uncovered evidence that SPA triggers birth by activating fetal immune cells called macrophages, which then leave the amniotic sac and travel to the uterus. There, the cells appear to trigger an inflammatory response that ultimately causes the cervix to open and contractions to begin.

Mendelson's group will chronicle its data implicating SPA in an upcoming Proceedings of the National Academy of Sciences.

Since a baby needs to breathe to survive outside the womb, it makes sense that lungs provide a labor-inducing signal only when they're mature. "The hypothesis is logical, yet novel, and supported by elegant experimental data," says Peter Mitchell of the University of Alberta in Edmonton.

Roberto Romero, chief of perinatology research at the Detroit campus of the National Institute of Child Health and Human Development, agrees that the observations on SP-A provide compelling evidence of a fetal trigger for the onset of labor. A key next step is "to confirm that this mechanism is also operative in women," he adds.

Mitchell notes that in women, the amniotic fluid concentration of SP-A begins to rise in the weeks, not days, before labor. He speculates that in mice and people, multiple mechanisms exist to ensure a timely birth.

Other studies on SP-A may provide insight into why infections increase a woman's risk of delivering prematurely. "We think bacteria are mimicking the effects of the surfactant protein," says Mendelson.