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Developmental Biology - Tobacco
Pregnancy Pushes Mom's Clock Forward
Little is known about circadian timing during pregnancy, however pregnancy induces changes in women's daily rhythms consistent with what is found in mice...
Expect another change in your body during pregnancy — getting up earlier, at least in your first trimester. In women, sleep onset becomes earlier during the first (weeks 4-13) and second trimesters (weeks 14-27) than before pregnancy. However it returns to a prepregnancy state during the third trimester (weeks 28 until delivery). Women also have reduced locomotor activity throughout pregnancy. Researchers at the Arts & Sciences and the School of Medicine, Washington University in St. Louis found impending motherhood induces changes in a mother's daily timing. And when these timing advances are disrupted, may even put a pregnancy at risk. These changes are conserved between mice and women.
The study results are published in the Journal of Biological Rhythms.
"This is a very important first step in understanding what is happening in term pregnancu, and it has a potential to inform our ability to intervene and prevent preterm birth in certain populations."
Carmel A. Martin-Fairey, Postdoctoral Fellow, Department of Biology, Arts & Sciences, and Obstetrics & Gynecology, School of Medicine, Washington University in St. Louis, Missouri, USA.
Nationwide, one in ten babies is born too early, before 37 weeks of pregnancy have been completed. Shift work and other disruptions of a regular sleep-wake schedule have been associated with preterm birth and other poor reproductive outcomes. But previously little was known about circadian timing during pregnancy.
How Monitoring Was Conducted
Nearly all organisms have a biological clock keeping daily time, driving 24 hour rhythms in behavior and physiology. These rhythms involve sleep and wake cycles, metabolism, hormone secretion, activity level and other physical processes — which may influence reproduction in many species, including humans.
The new study tracked 39 St. Louis area women as part of a larger, ongoing study of 1,000 births. Study participants wore wristwatches that continuously monitored their daily activity and rest for two full weeks before they attempted to conceive. Once the women found out they were pregnant, they again donned the watches for the duration of their pregnancies up until delivery.
In mice, the experimental setup was very similar, with researchers monitoring both pre-pregnancy and during pregnancy activity - in part by observing the time that the mice spent on a running wheel. The study found that both mice and women both shift their daily schedule earlier by as much as a few hours during the first trimester of their prenancy. In mice,this advance in the daily rest-activity pattern was detectable by the third day of pregnancy and persisted until 10 days before delivery. Similarly, the advance of the daily schedule in pregnant women gradually returned to normal before delivering.
"For the mice at least, the fact their activity advanced so early in pregnancy was surprising. We had no idea."
Sarah England, the AlanA. and Edith L. Wolff Professor of Medicine in obstetrics and gynecology; Associate Program Director, the March of Dimes Prematurity Research Center, School of Medicine; and co-author of the study.
"What happens in early pregnancy is they shift their total activity into earlier in the day," explains Erik Herzog, professor of biology in Arts & Sciences and lead author of the new study. "But they don't seem to sleep more or be more active during their early pregnancy. It's just a change in their daily timing. Later in pregnancy, that's when we start to see they are carrying a load and running less," he adds. "So they seem to be separable processes."
Certainly, a wearying workload can cause a childbearing mother to alter her schedule and sleep-rest patterns. But Herzog says the study shows it's more than that because of how early in the pregnancy the clock shift occurs. "There's the fatigue perhaps, or extra work that's required to carry a baby. But there's something about the daily timing system that's changing early in pregnancy the clock probably due to the hormones that are associated with pregnancy."
Researchers also observed the total amount of activity during pregnancy was significantly reduced — both in mice and women.
"In mice it was centered around late gestation, whereas in women it was significantly reduced across the entire gestation."
Carmel A. Martin-Fairey.
First Step In Understanding Pregnancy Circadian Rhythms
So the new research results provide a look into potential medical issues as they indicate pregnancy induces change in daily rhythms, altering sleep time and amount of activity.
"This finding is fascinating because while we know that miscarriage, preterm birth and other serious complications of pregnancy are linked to disruptions in a mom's circadian rhythm, we don't know how it works. This study takes us one step closer to understanding how normal circadian rhythm supports healthy pregnancy."
Kelle H. Moley MD, Chief Scientific Officer, March of Dimes.
Researchers also want to understand the impact of shift work and other high-risk time disruptions on preterm birth. "In preterm birth, there is a health disparity with African-American women having a higher rate," says England. "We are well-situated in St. Louis to delve into some of the mechanisms underlying this disparity."
According to Emily S. Jungheim MD, associate professor in the department of obstetrics and gynecology in the school and a co-author on the study: "Sleep in medicine is poorly studied. Even among healthy women an men - those who eat well, who exercise — the one thing they're willing to do without a second thought is skimp on their sleep. A lot of people don't pay attention to how important it is."
Abstract
Daily rhythms generated by endogenous circadian mechanisms and synchronized to the light-dark cycle have been implicated in the timing of birth in a wide variety of species. Although chronodisruption (e.g., shift work or clock gene mutations) is associated with poor reproductive outcomes, little is known about circadian timing during pregnancy. This study tested whether daily rhythms change during full-term pregnancies in mice and women. We compared running wheel activity continuously in both nonpregnant (n = 14) and pregnant (n = 13) 12- to 24-week-old C57BL/6NJ mice. We also monitored wrist actigraphy in women (N = 39) for 2 weeks before conception and then throughout pregnancy and measured daily times of sleep onset. We found that on the third day of pregnancy, mice shift their activity to an earlier time compared with nonpregnant dams. Their time of daily activity onset was maximally advanced by almost 4 h around day 7 of pregnancy and then shifted back to the nonpregnant state approximately 1 week before delivery. Mice also showed reduced levels of locomotor activity during their last week of pregnancy. Similarly, in women, the timing of sleep onset was earlier during the first and second trimesters (gestational weeks 4-13 and 14-27) than before pregnancy and returned to the prepregnant state during the third trimester (weeks 28 until delivery). Women also showed reduced levels of locomotor activity throughout pregnancy. These results indicate that pregnancy induces changes in daily rhythms, altering both time of onset and amount of activity. These changes are conserved between mice and women.
Authors
Carmel A. Martin-Fairey, Peinan Zhao, Leping Wan, Till Roenneberg, Justin Fay, Xiaofeng Ma, Ronald McCarthy, Emily S. Jungheim, Sarah K. England and Erik D. Herzog.
Acknowledgements
The authors thank Drs. Deborah Frank and Antonina Frolova and members of the Herzog and England labs for helpful discussions and comments on drafts of the manuscript. This work was supported, in part, by the March of Dimes Prematurity Research Center at Washington University. Dr. Carmel A. Martin-Fairey was supported, in part, by T32 HD049305 an F32 HD093269-01.
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