Placental molecule drop tied to timing of labor
Researchers report that falling NAD+ levels in the placenta may help set off labor and could point to ways to assess preterm birth risk.
By Priya Raghavan · Science Reporter
3 min read
A sharp fall in a metabolic coenzyme in the placenta may help start labor, according to a study co-led by researchers at UT Southwestern Medical Center. The finding matters because it could give doctors new clues for estimating delivery timing and identifying pregnancies at risk of ending too soon.
The study, published in Science, focused on nicotinamide adenine dinucleotide, or NAD+, a molecule used by cells in energy production and many chemical reactions. UT Southwestern said the work was co-led by Samir Parikh, chair and professor of internal medicine and professor of pharmacology at the medical center, and Erin Ciampa of Harvard Medical School and Beth Israel Deaconess Medical Center.
A possible placental clock
Pregnancy length tends to be fairly consistent within mammal species, UT Southwestern said. Human pregnancies average about 40 weeks, while mouse pregnancies average about 18.5 days.
Scientists have known that prostaglandins, hormone-like lipids, help activate labor and are used medically to induce it. The unresolved question has been what prompts reproductive tissues to increase prostaglandins near the usual end of pregnancy, according to the researchers.
To study that process, Parikh, Ciampa and colleagues measured molecules in mouse placentas from the second trimester through full term. UT Southwestern said the team identified a steep late-pregnancy decline in NAD+ and in precursor molecules that help produce it.
The researchers then examined placentas from women who delivered by cesarean section at different stages of pregnancy before labor had begun. UT Southwestern said those samples showed a similar pattern: NAD+ and its precursors decreased close to the point when natural labor would have been expected.
Mouse experiments altered pregnancy length
The team tested whether NAD+ helped control the timing of birth by lowering the molecule in mouse placentas. According to UT Southwestern, the researchers used both a drug and genetic changes to reduce NAD+ levels.
In both approaches, pregnancy in mice was shortened by more than one day on average, a meaningful shift given the normal mouse gestation length of about 18.5 days, the medical center said. In a mouse model of preterm birth, adding NAD+ precursors extended pregnancy by nearly one day, according to the study summary.
Those experiments suggest that NAD+ helps sustain pregnancy and that its decline can help initiate labor, UT Southwestern said. Parikh said the findings identify “a metabolic mechanism that may influence the length of pregnancy in both health and disease.”
Link to prostaglandins
The researchers also connected the NAD+ drop to 15-PGDH, a placental enzyme that uses NAD+ to break down prostaglandins. UT Southwestern said the team’s results suggest that when NAD+ falls late in pregnancy, 15-PGDH loses its ability to keep prostaglandins in check.
That change would allow prostaglandin levels to rise and trigger labor, according to the researchers. Parikh described the NAD+ decline as a possible tipping point in the nutritional balance between mother and fetus, with labor beginning when fetal metabolic demands outweigh the mother’s.
The authors said monitoring parts of the NAD+-prostaglandin pathway could one day help predict which patients face higher risk of preterm labor or help full-term patients better estimate when delivery may occur. UT Southwestern also said NAD+-boosting precursors might be explored as a way to prolong at-risk pregnancies, while NAD+ depletion could be studied as a possible method for inducing labor when needed.
The publication is titled “Placental nicotinamide adenine dinucleotide modulates the timing of labor.” Its listed first author is Erin J. Ciampa.
This story draws on original reporting from Medical Xpress.