In animal studies, maternal sleep apnea may cause ‘constellation deficits’ in male offspring

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Sleep apnea, a common disorder in which a person stops and starts breathing repeatedly while sleeping – often hundreds of times a night – is a growing problem during pregnancy. Researchers at the University of Wisconsin School of Veterinary Medicine are discovering how low blood oxygen levels caused by apnea affect the nervous system of offspring.

The results offer advice for doctors to help mitigate the risks to the children of a significant number of expectant parents. In the third trimester, sleep apnea occurs in about 15% of normal pregnancies and 60% of high-risk pregnancies.

Several out-of-school studies have shown, using a rat model, that sleep apnea during pregnancy can have a variety of adverse effects – from high blood pressure to brain inflammation to modification of the microbiome of the intestinal tract – on the male offspring. The researchers studied both male and female offspring, but found the most pronounced effects in males, with many problems not appearing until adulthood. The reason for this remains under investigation.

Jyoti Watters

More recently, a study published in the journal PLOS Biology and led by Michael Cahill, Jyoti Watters and Tracy Baker, professors in the Department of Comparative Biosciences, shed light on the cognitive and behavioral impacts that sleep apnea during pregnancy can have on offspring. The researchers exposed pregnant rats in the second half of their pregnancy to short, intermittent periods of low oxygen that mimics the low oxygen levels seen in sleep apnea (which does not occur naturally in rats). .

The male offspring of these rats were more likely to exhibit autism-like behavioral changes than female offspring or offspring whose mothers were not exposed to low oxygen levels. These behavioral changes, including abnormal vocalization patterns, impaired memory, reduced social interest, and increased repetitive behaviors, were often first observed shortly after birth and continued into adulthood. .

“Our data provide clear evidence that maternal sleep apnea may be an important risk factor for the development of neurodevelopmental disorders, particularly in male offspring,” Cahill states in a PLOS Biology. Press release.

Michael Cahill

In addition to these behavioral changes, the study found physical abnormalities in the brain cells of the offspring of mothers in which they mimicked sleep apnea.

Dendritic spines, part of the neuron responsible for receiving and acting on signals from other neurons, were found in higher density in the cerebral cortex and with atypical size and structure compared to offspring born from the control rats. These changes were observed in both male and female offspring; however, the effect was significantly worse in men. An abnormal increase in the density of dendritic spines in this region of the brain has also been identified in autism in humans.

Although it remains unclear how exposing pregnant rats to the recurrent low oxygen levels that occur in sleep apnea caused these changes, during normal brain development the number of dendritic spines is “pruned” or reduced – a process that investigators believe is lacking in sleep apnea offspring. experimental rats.

Tracy Baker

Watters and Baker discuss other far-reaching impacts of sleep apnea during pregnancy and explain why these seem to only affect men.

“We looked at several areas, one of the main ones being the respiratory function of the offspring,” says Watters.

If your parents have sleep apnea, you are also more likely to develop it. However, no specific genetic mutation has been identified. In a study recently submitted for publication, Baker and Watters showed that mothers with sleep apnea during pregnancy can transmit the disease to their offspring simply due to the in utero experience of intermittent oxygen deprivation.

“It was very interesting for us to be able to link intermittent low oxygen levels in the mother to an increased risk of development of sleep apnea in the adult male offspring, because it’s something that doesn’t has never been conceived before,” says Watters.

Satish Kumar

A study led by colleague Sathish Kumar, a professor of comparative biosciences at UW-Madison, found that low maternal intermittent oxygen levels also increased the risk of developing high blood pressure in adult men.

“This is another aspect that our work tries to address: how and why does this constellation of deficits occur almost exclusively in male offspring? said Baker.

As researchers continue to investigate, Baker suggests that the effect of maternal sleep apnea on the brains of developing offspring may be an important root cause. Because the brain controls every organ system in the body, the inflammatory response in the offspring’s brain can have a cascading effect throughout the body.

A worldwide increase in sleep apnea, partly due to an increase in obesity, makes understanding the risks of maternal sleep apnea particularly important.

“One of the main goals of our research is to educate doctors who care for pregnant women,” says Watters. “They should ask their patients questions about their sleep to determine if they should be screened for sleep apnea and encourage them to adhere to treatment.”

Although treatment for sleep apnea is readily available (most often in the form of a continuous positive airway pressure or CPAP machine), up to 50% of those diagnosed go untreated in part due to sleep apnea. discomfort and feelings of claustrophobia when wearing the CPAP mask. And many patients are not diagnosed at all.

Baker and Watters are collaborating with a Texas obstetrician-gynecologist to share their research and determine if the results from the rat model apply to humans.

In July, Baker received a patent for a potential therapy to treat sleep apnea in humans, a positive step in the effective treatment of the disease. Baker shares the invention with colleagues Gordon Mitchell, professor of neuroscience at the University of Florida, and Daryl Fields, a University of Pittsburgh neurosurgeon who earned his doctorate in neuroscience at UW-Madison.

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