Protein Secreted By Lungs Triggers Labor
The initiation of term labor is carefully timed to begin only after a baby is sufficiently mature to survive outside the womb. Previous studies suggested that the signal for labor in humans may arise from the unborn baby, but the nature of the signal and actual mechanism was unclear, Dr Mendelson says.
Babies' lungs secrete substance
In their study, UT Southwestern researchers found evidence that a substance secreted by the lungs of a developing baby contains the key signal that initiates labor. The substance, called surfactant, is essential for normal breathing outside the womb.
"We found that a protein within lung surfactant serves as a hormone of labor that signals to the mother's uterus when the fetal lungs are sufficiently mature to withstand the critical transition to air breathing,"Dr Mendelson says.
"No one really understands what causes normal or preterm labor. There may be several chemical pathways that lead to labor, but we think that this surfactant protein, which is also produced by the fetal lung in humans, may be the first hormonal signal for labor," says Dr Mendelson, who is co-director of the North Texas March of Dimes Birth Defects Center at UT Southwestern.
Protein also kills bacteria, viruses
In humans the signaling protein, called surfactant protein A, or SP-A, also helps immune cells, called macrophages, fight off infections in the lungs of children and adults by gobbling up bacteria, viruses and fungi that infiltrate the lung airway.
"Women who go into preterm labor frequently have an infection of the membranes that surround the fetus, and the number of macrophages in the wall of the uterus increases with the initiation of preterm labor. When women go into labor at term, they also have an increase in macrophages in the uterus," Dr Mendelson says.
This led the researchers to investigate whether there was a connection between what happens during normal labor at term and in infected mothers who go into early labor.
"This also raised the question: If bacterial infection can cause increased macrophage infiltration of the uterus in preterm labor, what is the signal for the enhanced macrophage migration to the uterus at term?" Dr Mendelson says.
In mice, the developing fetal lung starts producing SP-A at 17 days gestation; full-term delivery occurs at 19 days. The developing human fetus starts producing SP-A in increasing amounts after 30 to 32 weeks of a 40-week normal gestation, at which time the baby's lungs are essentially developed. As the fetus "breathes" amniotic fluid in the womb, the protein is released into the fluid.
"The SP-A protein binds to macrophages in the amniotic fluid, macrophages that come from the fetus itself," says Dr Jennifer Condon, a postdoctoral researcher in biochemistry and the study's lead author.
The macrophages, "activated" by the protein, make their way through the amniotic fluid to the wall of the uterus. Once embedded there, they produce a chemical that stimulates an inflammatory response in the uterus, ultimately leading to labor.
The researchers also found that injecting a pregnant mouse with SP-A before day 17 of the pregnancy caused the mouse to deliver early. Injection of pregnant mice with an antibody that blocks SP-A function caused them to deliver late.
Identifying the receptors on the macrophages to which the SP-A protein binds will be the next step, Dr Mendelson says.
"We think that bacteria may be binding to the same receptor on the macrophages to cause preterm labor in women. The bacteria mimic the function of SP-A, initiating the chemical reactions that lead to premature labor. If we knew more about this receptor on amniotic fluid macrophages, we may be able to design therapies or inhibitors to block preterm labor," she says.