Researchers identify molecular mechanisms within fetal lungs responsible for initiating labour.
Each year about one in every nine infants in the United States is born preterm (before 37 weeks), according to the Centers for Disease Control and Prevention. Premature birth can cause brain hemorrhage and respiratory distress for babies, as well as long-term conditions such as cerebral palsy, chronic lung disease, and impaired vision. Now, a new study from researchers at UT Southwestern Medical Center have identified two proteins in a fetus’ lungs responsible for initiating the labour process, providing potential new targets for preventing preterm birth. The opensource study is published in the Journal of Clinical Investigation.
Previous studies have suggested that signals from the fetus initiate the birth process, but the precise molecular mechanisms that lead to labour remained unclear. The current study used mouse models to find that the two proteins, steroid receptor coactivators 1 and 2 (SRC-1 and SRC-2), control genes for pulmonary surfactant components that promote the initiation of labour. Surfactant is a substance released from the fetus’ lungs just prior to birth that is essential for normal breathing outside the womb.
The team state that the results provide compelling evidence that the fetus regulates the timing of its birth, and that this control occurs after these two gene regulatory proteins, SRC-1 and SRC-2, increase the production of surfactant components, surfactant protein A and platelet activating factor. They go to add that by understanding the factors and pathways that initiate normal-term labour at 40 weeks, the medical community can gain more insight into how to prevent preterm labour.
The results showed that the proteins SRC-1 and SRC-2 activate genes inside the fetus’ lungs near full term, resulting in an increased production of surfactant components, surfactant protein A (SP-A), and platelet-activating factor (PAF). The team state that both SP-A and PAF are then secreted by the fetus’ lungs into the amniotic fluid, leading to an inflammatory response in the mother’s uterus that initiates labour.
The data findings also showed that a deficiency of both SRC-1 and SRC-2 inside the fetus’ lungs drastically decreased the production of SP-A and PAF, causing a one- to two-day labour delay in mouse models, comparable to a three- to four-week labour delay in women. The team found that injecting either SP-A or PAF into the amniotic fluid of the deficient mice allowed the mothers to deliver on time.
The researchers surmise that the findings further define the underlying molecular mechanisms by which fetuses control the timing of birth. They go on to conclude that future research will include defining how fetal signals are transmitted to the mother’s uterus, and relating these findings to the causes of preterm labour.
Source: UT Southwestern Medical Center