Research published today in the journal PLosMed investigates the impact of high glucose in mothers with gestational diabetes mellitus (GDM) and changes to infants DNA.

GDM is becoming more frequent around the world alongside a rise in obesity and can increase the risk of complications during pregnancy and childbirth as well as increasing the risk of metabolic disease in the child in later life. High levels of glucose in mothers with GDM have been suggested to trigger epigenetic changes in the developing fetus (chemical modifications to the genetic blueprint of the fetus that function of genes activity) resulting in adverse health outcomes for the child.

Researchers from the University of Southampton and King’s College London studied data from over 550 pregnant women with obesity and their children, from the UK Pregnancies Better Eating and Activity Trial (UPBEAT). The trial aims to improve the diet and physical activity of obese pregnant women across the UK. Compared to women in a control group, who made no changes to their lifestyle during pregnancy, women who were supported in changing their diet to lower glycemic index foods that are broken down less quickly by the body, a reduced fat intake and increasing their physical activity put on less weight and were metabolically healthier.

In this new study, researchers compared the level and pattern of DNA methylation, a major epigenetic mechanism which controls gene activity, in the newborn infants from mothers who developed GDM with those that did not. They then looked at whether a dietary and physical activity intervention during pregnancy altered these modifications in infants born to mothers who developed GDM.

The results showed that GDM and high glucose levels in mothers were linked to changes in the level and pattern of functional modification to the infants DNA. Moreover, they found that the dietary and exercise intervention significantly reduced these methylation changes in the infant associated with GDM in the mothers.

Karen Lillycrop, Professor of Epigenetics at the University of Southampton said, “These findings suggest that improvements to diet and physical activity can have an impact on the development of their children.

“These are very encouraging finding and further studies are now needed to establish whether reducing these epigenetic changes through a healthier lifestyle during pregnancy are accompanied by improved health outcomes for the children in later life.”

Professor Lucilla Poston, Tommy’s Chair of Maternal & Fetal Health and lead investigator of the UPBEAT trial at King’s College London, said: “we have known for some time that children of mothers who had gestational diabetes are a greater risk of obesity and poor control of glucose; this new research implies that epigenetic pathways could be involved.”

Tommy’s chief executive Jane Brewin said: “Obesity during pregnancy can have lifelong negative impacts on mother and baby — so one of the best things mums can do is to improve their health, including their weight, before embarking on a pregnancy. However, this study shows that mums who are overweight and their babies can still benefit from adopting a healthy diet while pregnant. All mums-to-be need access to healthy eating advice, and those who are overweight should be given non-judgemental practical support and encouragement to eat healthily during pregnancy.”

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Materials provided by University of Southampton. Note: Content may be edited for style and length.

In an article in Pregnancy Hypertension, a team of researchers at the Medical University of South Carolina (MUSC) found that expression of a set of genes previously studied in the setting of early onset and severe preeclampsia is significantly affected by vitamin D status during late-stage pregnancy.

Exactly how preeclampsia develops is unclear. Recent evidence points to poor development of blood vessels in the placenta — the organ that nourishes the fetus throughout pregnancy. This leads to hypertension and several other complications in the mother. The only cure for preeclampsia is to deliver the fetus, which can be dangerous if done too early.

In a previous study that was supported by pilot funding from the South Carolina Clinical & Translational Research Institute (SCTR), the research team led by Kyu-Ho Lee, M.D., Ph.D., assistant professor in the departments of Pediatrics and Obstetrics and Gynecology at MUSC found that the expression of three genes — NKX2-5, SAM68, and sFLT1 — are highly correlated in the setting of early-onset and severe preeclampsia (EOSPE), with sFLT1 being an identified marker for preeclampsia risk. In the current study, which also received SCTR support, the authors examined the expression of these genes in healthy pregnant women.

“Having observed the correlated expression of these genes in preeclampsia, we wanted to see the pattern of expression of these genes in normal pregnancy,” said Lee. “We had a secondary goal of seeing whether vitamin D status affected the expression of these genes.”

The sFLT1 protein interferes with the activity of vascular endothelial growth factor (VEGF), which is an important regulator of blood vessel development. This reduces vascular growth in the placenta. The amount of sFLT1 in the placenta is regulated in part by SAM68 and NKX2-5, also known as the tinman gene. This hypothesized NKX2-5/SAM68/sFLT1 gene “axis” may contribute to the development of preeclampsia.

“NKX2-5 might be controlling the regulation of sFLT1 and SAM68 in such a way that in preeclampsia, the expression levels of those genes go awry and tilt the vascular development in a direction that might trigger preeclampsia,” said Lee.

Vitamin D affects many aspects of the mother’s health during pregnancy. To investigate how the gene axis is affected by maternal vitamin D status, Lee’s team studied placental samples from 43 pregnant women enrolled in a clinical trial at MUSC organized by their collaborator, MUSC Health neonatologist Carol L. Wagner, M.D., a professor in the Department of Pediatrics. Half of the women received a high dose of vitamin D3 (4,000 IU/day), and the other half received a placebo. The study group included African American, Hispanic American and Caucasian American women.

In contrast to their previous study, the team did not detect significant levels of NKX2-5 in placental tissue samples before a healthy delivery. This finding suggests that NKX2-5 expression is important in early at-risk pregnancies but not healthy pregnancies. However, the team did observe a strong positive correlation between SAM68 and sFLT1 in all study participants.

“The tight correlation between SAM68 and sFLT1 makes us think that there’s a functional relationship between these genes,” said Lee.

Interestingly, when assessed at the last visit before delivery, women who were vitamin D deficient (<100 nmol/L of the vitamin D metabolite 25[OH]D) had significantly higher expression of sFLT1 and lower expression of VEGF in the placenta than women who were vitamin D sufficient.

This study provides novel insight into the activity of the NKX2-5/SAM68/sFLT1 gene axis during healthy pregnancies in a diverse group of women and how it may be affected by the vitamin D status of the mother.

“These results raise the possibility that vitamin D somehow directly regulates sFLT1 and/or SAM68 expression at some level,” said Lee. “However, at this point, we haven’t addressed the exact molecular relationship.”

Future studies might investigate the relationship between vitamin D status and the expression of sFLT1 and SAM68 in mothers diagnosed with preeclampsia.

“Ideally, you would want a study with an equal number of diseased versus control pregnancies that had differential levels of vitamin D,” said Lee. “Then we could look at the incidence of disease in correlation to the levels of vitamin D they achieved and the amount of gene expression that we had observed.”

The team’s current findings contribute to a basic biological understanding of the development of pregnancy and preeclampsia. Lee believes that this understanding will improve the standard of care for treating preeclampsia.

“We can begin to develop clinical markers that would help us gauge the health of a pregnancy during its course,” said Lee. “This could provide warning signs for an increasing risk of pregnancy complication.”

But sometimes bats collide with large walls even though they detect these walls with their sonar system. Researchers from Tel Aviv University (TAU) have concluded that these collisions do not result from a sensory limitation but rather from an error in acoustic perception.

The study was led by Dr. Sasha Danilovich, a former PhD student in the lab of Prof. Yossi Yovel, Head of the Sagol School for Neuroscience and faculty member at the School of Zoology at the George S. Wise Faculty of Life Sciences. Other participants included Dr. Arian Bonman and students Gal Shalev and Aya Goldstein of the Sensory Perception and Cognition Laboratory at the School of Zoology and the Sagol School of Neuroscience. The paper was published on October 26, 2020, in PNAS.

The TAU researchers released dozens of bats in a corridor blocked by objects of different sizes and made of different materials. To their surprise, the researchers discovered that the bats collided with large sponge walls that produce a weak echo as if they did not exist. The bats’ behavior suggested that they did this even though they had detected the wall with their sonar system, indicating that the collision did not result from a sensory limitation, but rather from an acoustic misperception.

The researchers hypothesize that the unnatural combination of a large object and a weak echo disrupts the bats’ sensory perception and causes them to ignore the obstacle, much like people who bump into transparent walls.

The researchers then methodically changed the features of the objects along the corridor, varying their size, texture and echo intensity. They concluded that the bats’ acoustic perception depends on a coherent, typical correlation of the dimensions with objects in nature — that a large object should produce a strong echo and a small object a weak echo.

“By presenting the bats with objects whose acoustic dimensions are not coherent, we were able to mislead them, creating a misconception that caused them to repeatedly try to fly into a wall even though they had identified it with their sonar,” Danilovich explains. “The experiment gives us a peek into how the world is perceived by these creatures, whose senses are so unique and different from ours.”

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Materials provided by American Friends of Tel Aviv University. Note: Content may be edited for style and length.