Circadian cycle can impact women trying to have babies
Posted by on May 31, 2012 - 6:05am

A new study shows that the biological clock is not the only clock women trying to conceive should consider. The circadian clock needs attention, too.

Epidemiological studies have shown female shift workers, such as nurses, and female flight attendants who work on long-distance east-west routes (i.e., those with constant jet lag) have fertility and menstrual issues. They are habitually out of sync with the external light cycle. But the role circadian rhythm disruption may play in their reproductive problems is a poorly studied area.

Research led by Northwestern U. circadian rhythm expert Fred W. Turek now draws a clear line between disrupted circadian rhythms and reproductive physiology. Turek and his colleagues are the first to show that if you disrupt the circadian clock environmentally in mice, with repeated changes in their light-dark cycles, there are problems with pregnancy outcomes.

And the effect can be dramatic. The researchers found evidence suggesting the severity of circadian disruption may be linked to the severity of pregnancy disruption: mice subjected to advances of the light-dark cycle had greater circadian clock disruption and lower reproductive success. This group’s pregnancy success rate was only 22 percent.

The study was published today in the journal PLoS ONE.

“Our results have important implications for the reproductive health of female shift workers, women with circadian rhythm sleep disorders and/or women with disturbed circadian rhythms for other reasons,” Turek said.

“If you disrupt your internal rhythms, there will be negative consequences -- that is very clear,” said Keith Summa, first author of the paper and an M.D./Ph.D. candidate working in Turek’s lab. “Our results suggest people should consider their biological rhythms for optimal health.”

The repeated shifting of the light-dark cycle shifts the biological clock throughout the body. This environmental disturbance is more relevant to shift workers and those frequently flying across time zones, the researchers note, than genetic disruption of the circadian clock, which also negatively influences reproductive function.

Turek, Summa and their colleague and co-author Martha H. Vitaterna studied three sets of normal laboratory female mice, all who had recently mated. The study was conducted over the course of 21 days, the duration of a typical pregnancy.

One set was a control group of 12 mice that experienced normal days of 12 hours of light, followed by 12 hours of darkness. The two other groups, of 18 mice each, also experienced days of 12 hours of light and 12 hours of darkness. But the phase-advanced group had its 12 hours of light start six hours earlier every five days. The phase-delayed group had its light start six hours later every five days. (There were a total of four phase shifts over the duration of the study.)

The researchers monitored the mice throughout the gestation period to count the number of full-term pregnancies. The results surprised them.

In the control mice, 90 percent of the matings led to full-term pregnancies. But in the phase-delay group, the pregnancy success rate was 50 percent, while in the phase-advanced group, it was only 22 percent.

“We were surprised at how dramatic the effect of manipulating the light-dark cycle was, especially in the phase-advanced group,” Summa said. “We expected a negative effect from the circadian clock disruption, but not this much.”

They next looked at a separate group of females in the phase-delay and phase-advance protocol to see how the animals responded to the repeated phase shifts. The researchers found the phase-advanced animals required one to two days longer, on average, to return to normal rhythms. This suggests the magnitude of circadian disruption is associated with the severity of pregnancy loss.

The next steps, the researchers say, are to identify specifically the stage at which pregnancy is affected and to understand exactly how circadian disruption results in the observed adverse effects.

“We’ve made an interesting observation, but what’s causing the reduced fertility?” Summa said. “We would like to determine where exactly the phase shifts and internal rhythm disruptions are having an effect.”

The March of Dimes Foundation and the Institute for Women’s Health Research at Northwestern University (the sponsor of this blog) supported the research.

The paper is titled “Environmental Perturbation of the Circadian Clock Disrupts Pregnancy in the Mouse.”

Megan Fellman is the science and engineering editor. Contact her at fellman@northwestern.e

Night Owls at Risk for Weight Gain
Posted by on May 21, 2011 - 8:57am

Staying up late every night and sleeping in is a habit that could put you at risk for gaining weight. People who go to bed late and sleep late eat more calories in the evening, more fast food, fewer fruits and vegetables and weigh more than people who go to sleep earlier and wake up earlier, according to a new Northwestern Medicine study.

Late sleepers consumed 248 more calories a day, twice as much fast food and half as many fruits and vegetables as those with earlier sleep times, according to the study. They also drank more full-calorie sodas. The late sleepers consumed the extra calories during dinner and later in the evening when everyone else was asleep. They also had a higher body mass index, a measure of body weight, than normal sleepers.

The study is one of the first in the United States to explore the relationship between the circadian timing of sleeping and waking, dietary behavior and body mass index. The study was published online in the journal Obesity and is expected to appear in a late summer print issue.

“The extra daily calories can mean a significant amount of weight gain – two pounds per month – if they are not balanced by more physical activity,” said co-lead author Kelly Glazer Baron, a health psychologist and a neurology instructor at Northwestern University Feinberg School of Medicine.

“We don’t know if late sleepers consume the extra calories because they prefer more high-calorie foods or because there are less healthful options at night,” said co-lead author Kathryn Reid, research assistant professor in neurology at the Feinberg School.

The study shows not only are the number of calories you eat important, but also when you eat them -- and that’s linked to when you sleep and when you wake up, noted senior author Phyllis Zee, M.D., professor of neurology and director of the Sleep and Circadian Rhythms Research Program at Feinberg and medical director of the Sleep Disorders Center at Feinberg and Northwestern Memorial Hospital.

“Human circadian rhythms in sleep and metabolism are synchronized to the daily rotation of the earth, so that when the sun goes down you are supposed to be sleeping, not eating,” Zee said. “When sleep and eating are not aligned with the body’s internal clock, it can lead to changes in appetite and metabolism, which could lead to weight gain.”

The research findings could be relevant to people who are not very successful in losing weight, Zee said. “The study suggests regulating the timing of eating and sleep could improve the effectiveness of weight management programs,“ she said.

The findings also have relevance for night-shift workers, who eat at the wrong time of day related to their bodies’ circadian rhythms. “It’s midnight, but they’re eating lunch,” Zee said. “Their risk for obesity as well as cardiovascular, cerebrovascular and gastrointestinal disorders is higher.”

The study included 51 people (23 late sleepers and 28 normal sleepers) who were an average age of 30. Late sleepers went to sleep at an average time of 3:45 a.m., awoke by 10:45 a.m., ate breakfast at noon, lunch at 2:30 p.m., dinner at 8:15 p.m. and a final meal at 10 p.m. Normal sleepers on average were up by 8 a.m., ate breakfast by 9 a.m., lunch at 1 p.m., dinner at 7 p.m., a last snack at 8:30 p.m. and were asleep by 12:30 a.m.

Participants in the study recorded their eating and sleep in logs and wore a wrist actigraph, which monitors sleep and activity cycles, for at least seven days.

Late sleepers function in society by finding jobs where they can make their own hours, Baron noted, such as academics or consultants. “They find niches where they can live this lifestyle, or they just get by with less sleep,” she said.

Northwestern researchers are planning a series of studies to test the findings in a larger community and to understand the biological mechanisms that link the relationship between circadian rhythms, sleep timing and metabolism.
by Marla Paul, health sciences editor, Feinberg School of Medicine. Contact her at marla-paul@northwestern.edu

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Circadian Rhythm and Breast Cancer
Posted by on August 16, 2010 - 10:38am

All living organisms have a circadian clock, sometimes called a biological clock, that is an important part of maintaining optimal health.   The circadian rhythm is a roughly 24-hour cycle in the biochemical, physiological, or behavioral processes of living things.   Although  circadian rhythms originate from within our bodies, they are synchronized to the environment by external cues, including the day-night cycle caused by the Earth's rotation.  Researchers are looking more closely at the role circadian rhythms play in the development of diseases such as breast cancer and also how factors such as hormones affect this biological clock.

Carla Finkielstein, a molecular biologist at Virgina Tech, has launched a research project to study how changes in circadian rhythms may contribute to the development of breast cancer in women.   According to Finkielstein, "There are a number of epidemiological studies that show women working night shifts have a higher incidence of breast cancer."  The question she asks is:   Can working odd hours actually alter a women's body chemistry--turning healthy cells into cancer cells?

With support from the National Science Foundation, she is using frog embryos to help figure out on a molecular basis the physiological changes in women who work night shifts.   She says studies show that night workers have abnormal levels of specific protein in their cells, which act by turning on and off genes that regulate how cells grow and divide.  Proper timing of cell division is a major factor contributing to the regulation of normal cell growth and is a fundamental process in the development of most cancers.  She explains," Our research explores ways in which the loss of circadian function impairs the death of cells in the cell cycle and leads to the accumulation of damaged, or cancerous, cells."

Where is this leading us, what is the clinical application?   "If we were to generate a panel of markers that we can follow regularly for women who works night shifts, it would enable us to record changes in circadian-controlled genes and thus predict whether a person is at risk of developing breast cancer, " Finkielstein said.   "If we see abnormal changes, all we may need to do is to alter this person's work schedule."

This study reinforces the important role circadian rhythm plays in sex and gender-based research.  In another example,  researchers at Northwestern University who are working in the lab of Dr. Fred Turek have determined that sex differences in hormone status in female mice are critical to better understanding stress or sleep deprivation.  There is growing evidence that circadian rhythm may play a part in other health issues like cardiovascular disease and diabetes.