Fetal lungs regulate molecular signals that initiate parturition
The intiation of birth (parturition)
Contrary to the popular themes that we cannot control where we are born at, or to whom we are born to, new scientific data shows that there is constant molecular talk between the mother and the near-term fetus and infact the fetus sends in crucial signals to initiate the process of labor.
Both at term and preterm, the initiation of labor is associated with an up regulated inflammatory response, a spike in the pro-inflammatory cytokines in amniotic fluid; infiltration of myometrium, cervix, and fetal membranes by neutrophils and macrophages and a decline in progesterone receptor function. But there is still no clear evidence of the actual molecular signals that cause the inflammatory response leading to labor at term.
Surfactant is a lipoprotein that reduces surface tension within the lung alveoli after birth and is essential for air breathing in the new-born. Thus preterm babies with surfactant deficiency have the risk of developing respiratory distress syndrome. However surfactant deficient mice have only a modest delay in parturition suggesting other important players. This creates a demand for understanding the molecular mechanisms regulating the initiation of birth to better manage or prevent preterm births.
New research suggests important roles for two transcription factors, SRC-1 and SRC-2
Carole Mendelson’s group from UT Southwestern Medical Center aimed to investigate the fetal molecular signals that kick start the inflammatory process prior to parturition. This study, supported by NIH and Prematurity Research Initiative grant, researched on steroid receptor coactivators 1 and 2 (Src-1 and Src-2), with important roles in the transcriptional regulation of Surfactant protein-A (SP-A), enzyme lysophosphatidylcholine acyltransferase-1 (LPCAT1) and platelet activating factor (PAF).
These proteins and enzymes, released by the fetus’ lungs upon maturation, have the capacity to activate immune cells that trigger a pro-inflammatory reaction in the mother’s amniotic fluid and through NF-kB pathway leads to myometrial cells’ contraction. They developed an Src-1 and Src-2 double-deficient mice that showed a significant delay in parturition (38 hours), comparable to a three to four week delay in humans, suggesting that the delay is caused by the fetus. When injected with SP-A or PAF into the amniotic fluid, these double-deficient embryos carrying mice showed increase in NF-kB activation, contractile gene expression, and a significant rescue of delayed parturition.
This study provides evidence that the mature fetal lungs initiate the cascade of events leading to parturition by sending molecular signals to the mother when they develop the capacity to produce enough surfactant protein to sustain air breathing.