Untangling the mysteries of labour onset
Dr. Donna Slater studies the intricacies of the mechanisms that trigger labour in pregnant women.
Story by Julie Sedivy/Illustration by Amanda Woodward
For roughly 38 weeks after conception, the human uterus serves as a protective nest for the developing fetus. How does the uterus know when it's time to stop playing the role of nurturing host and turn on the "Big Squeeze" to evacuate its tenant?
Exactly how this happens is still quite mysterious to scientists who are puzzling through the precise mechanisms that trigger labour. It's an important phenomenon to understand: labour begins too early in about 6% to 8% of Canadian pregnancies, and too late in another 1%. Mistiming delivery by even a few weeks can result in dangerous complications for the baby and the mother.
Scientists have known for some time that a group of hormones known as prostaglandins play a role in the onset of labour by causing the cervix to soften (or "ripen") and stimulating contractions of the uterus. In the past, preterm labour was treated with medications that suppressed the production of prostaglandins. However, it's now clear that prostaglandins do double duty and also help the fetus to develop. As a result, suppressing prostaglandins can cause serious birth defects, including heart abnormalities and kidney problems.
According to AHFMR Scholar Dr. Donna Slater, the key to more effective treatments lies in better understanding of the complex effects of prostaglandins on the uterus. She believes that targeting prostaglandins more precisely is a promising approach. Her research is making progress in identifying the parts of this intricate system that are responsible for stimulating uterine contractions as opposed to those that perform other functions.
Cells in the uterus produce prostaglandins from fatty acids using enzymes (proteins that speed up chemical reactions). This process involves numerous steps and several enzymes that may have different effects on the uterus. Dr. Slater wants to identify which of these enzymes is associated with labour onset and which affect fetal development. To do so, she analyzes slivers of uterine tissue that have been donated to science by women who have undergone C-section deliveries. By comparing the tissue samples from women who had planned C-sections before going into labour with samples from women who had C-sections after labour began, Dr. Slater can compare what is happening in the tissue before and after labour onset.
The enzymes responsible for triggering labour are likely those from later stages of the production of prostaglandins. The problem with some medications that are used to delay labour is that they also target the enzymes from the earlier steps of prostaglandin production. This may affect other important functions of prostaglandins, such as fetal development.
To make matters more complicated, one of Dr. Slater's most important discoveries is that one type of prostaglandin plays a role both in contracting and relaxing the uterus. Given that prostaglandins may play a part in both maintaining a healthy pregnancy and bringing on labour, casting the net too widely and suppressing all prostaglandins may turn out to be an ineffective strategy as well as potentially dangerous. The key is to find a balance and to target the appropriate functions within the prostaglandin pathway.
Dr. Slater is attracted to the complexity of this puzzle as well as to the painstaking laboratory techniques involved in putting the pieces together. "I like the part of this research that involves working with my hands," she grins. "I'm like a mechanic in the lab." Many pieces still need to be put in place. The prostaglandin pathway is not the only system involved in labour onset. Another is the oxytocin pathway, which can stimulate labour when a woman's pregnancy has gone past term or when labour is not progressing well on its own. It also turns out that the prostaglandin and oxytocin pathways may "talk to each other", adding yet another level of complexity to the picture, and promising to keep Dr. Slater happily tinkering in the lab for years to come.
A new way of supporting research
Dr. Donna Slater is a member of the Preterm Births and Healthy Outcomes (PreHOT) team which receives funding through the AHFMR Interdisciplinary Team Grant program. This multi-million dollar initiative provides opportunities for collaborative teams of researchers from different disciplines and institutions to address important research questions—questions closely linked with high-priority health problems in Alberta. Alberta Health and Wellness contributes funding to support the team grant program.
For more information on the team grant program go to www.ahfmr.ab.ca/grants/team.php