University at Buffalo - The State University of New York

Published: January 17, 2008

By LOIS BAKER
Contributing Editor

In the 21st century, human tissue can be generated from stem cells and severed limbs are successfully reattached, while the physiological processes governing life’s most fundamental event—childbirth labor—remain a medical mystery.

More than 500,000 babies, or one of every eight infants born in the U.S., were born prematurely in 2004, the most recent year for which statistics are available. The causes of 30-50 percent of preterm births are unknown.

Glenna Bett, assistant professor of gynecology and obstetrics in the School of Medicine and Biomedical Sciences, hopes to shed new light on this age-old problem. Supported by grants totaling $438,500 from the National Institutes of Health and March of Dimes, she is investigating the basic cellular mechanics that instigate the muscle contractions of labor.

Her work is aimed at developing drugs that can prevent the premature onset of those contractions.

“Identifying the molecular bases of changes in uterine muscle activity during pregnancy offers opportunities for rational drug design for the pharmacological treatment of preterm labor,” said Bett. “Therapeutic interventions that target earlier steps in parturition should prove more effective in delaying birth than currently used agents, which have only limited effectiveness.

“A fundamental problem in developing therapeutic interventions for preterm labor,” Bett continued, “is that the molecular bases of the mechanisms involved in parturition are unknown.”

Uterine contraction, like all smooth-muscle contraction, is primarily an electromechanical event. Although hormonal and biochemical changes play a vital role in regulating and developing conditions leading to labor, she said, the speed and coordination of a process called excitation-contraction coupling in uterine muscle tissue indicates that the short-term signals for contraction are carried by ion channels.

Excitation-contraction coupling is a term used in muscle physiology that describes the process of converting an electrical stimulus (a nerve impulse) to a mechanical response (muscle-fiber contraction), Bett explained, and ion channels are proteins that act as pores in a cell membrane, permitting selective passage of potassium, sodium and calcium molecules in and out of the cell. This process of ion exchange produces and regulates electrical current.

“Spontaneous premature labor must, therefore, result from a perturbation in the normal timing and regulation of the electromechanical profile of the uterus,” said Bett.

“Efficient and well-timed excitation-contraction requires two equally important components: an excitatory action to initiate an influx of ions into nerve cells and subsequently contraction, and a relaxing action to return the membrane to the resting state, allowing ions to exit. This whole process is called repolarization.

“Without adequate and timely repolarization,” said Bett, “the excitation-contraction coupling sequence will become dysfunctional, leading to abnormal contraction.”

Bett has shown in preliminary data that ion-channel expression changes 150-fold during gestation. She will study these changes during pregnancy by comparing uterine muscle tissue obtained from nonpregnant women through hysterectomy with uterine tissue from women whose babies were delivered by Caesarean section.