DALLAS Nov. 15, 2010 Tiny molecules called microRNAs act together with hormones to control the onset of labor, raising the prospect that RNA-based drugs might be able to prevent premature labor, researchers at UT Southwestern Medical Center have discovered in a preclinical study.
"With these findings, we understand better the system that controls labor, so with future research we might have the potential to manipulate it and prevent preterm birth," said Dr. Carole Mendelson, professor of biochemistry and obstetrics and gynecology at UT Southwestern and senior author of the study, which appears in an online issue of the Proceedings of the National Academy of Sciences.
Using pregnant mice as well as human uterine tissue, the researchers uncovered a feedback cycle involving microRNAs, proteins called ZEB1 and ZEB2, and the pregnancy-maintaining hormone progesterone, as well as genes and other factors that control contraction of the uterus.
"We've been struggling for a long time to understand how progesterone keeps the uterus from contracting during most of pregnancy," Dr. Mendelson said. "Our findings indicate that progesterone controls a family of microRNAs whose levels dramatically increase right before labor. At the same time, levels of the microRNAs' targets, the ZEB proteins, decrease. This enables uterine contractions."
MicroRNA is one form of RNA, a chemical cousin of DNA. MicroRNAs interact with other protein-making molecules in cells, helping to fine-tune the expression of networks of genes and control cell function, Dr. Mendelson said.
In the new study, the researchers measured microRNA levels in the uteri of mice in mid-pregnancy and near labor. As labor approached, the level of a group of microRNAs called the miR-200 family greatly increased. When the researchers artificially stimulated premature labor, the miR-200 levels also increased.
The miR-200s block the production of two proteins
|Contact: Aline McKenzie|
UT Southwestern Medical Center