Author: IGIHE

{When a baby is born small, it’s often attributed to genetic factors or maternal risk factors like poor nutrition or smoking. But a twin study led by researchers at Boston Children’s Hospital now find that slower transport of oxygen from mother to baby across the placenta predicts slower fetal growth, as well as a smaller brain and liver.}

The study, published in Scientific Reports is the first to make a direct connection between birth outcomes and placental oxygen transport.

By studying identical twins, the researchers were uniquely able to control for both genetic factors and maternal risk factors. Although identical twins also share a placenta, it is divided into two separate compartments, and one may be healthier than the other.

P. Ellen Grant, MD, director of Boston Children’s Fetal-Neonatal Neuroimaging and Developmental Science Center, and Elfar Adalsteinsson, PhD at MIT have developed a noninvasive method that uses MRI to map the timing of oxygen delivery across the placenta in real time. Using this technique, called Blood-Oxygenation-Level-Dependent (BOLD) MRI, they showed that dysfunctional placentas have large regions with slow oxygen transport to the fetus.

“Until now, we had no way to look at regional placental function in vivo,” says Grant. “Prenatal ultrasound or routine clinical MRI can assess placental structure, but cannot assess regional function, which is not uniform across the placenta. Doppler ultrasound, the current clinical method of assessing placental function, measures blood flow in the umbilical arteries and other fetal vessels, but it cannot tell how well oxygen or nutrients are being transported from mother to fetus.”

{{Real-time placental oxygen mapping}}

In the new study, part of the NIH-funded Human Placenta Project, Grant, co-senior investigator Julian Robinson, MD, chief of obstetrics at Brigham and Women’s Hospital (BWH), and their colleagues followed seven sets of identical twins all the way to birth, specifically tracking pregnancies in which one twin was smaller than the other.

At 29 to 34 weeks of pregnancy, the seven mothers underwent BOLD MRI for about 30 minutes. While they inhaled pure oxygen for 10-minute stretches, Grant’s team measured how long it took oxygen to reach its maximum concentration in the placenta, known as the time to plateau (TTP), and then how long it took for the oxygen to pass through the umbilical cord into the fetus and penetrate the brain and liver. Researchers led by Polina Golland, PhD, at MIT CSAIL used image-correction algorithms developed by MIT to adjust for fetal motion.

They found that a longer TTP in the placenta correlated with lower liver and brain volumes and lower newborn birth weights. TTP also correlated with placental pathology when placentas were examined after birth by placental pathologist Drucilla Roberts, MD, at Massachusetts General Hospital (MGH).

Grant hopes her team’s work will be used to better understand pregnancy risk factors, develop a prenatal test for mothers in whom placental dysfunction is suspected and ultimately improve prenatal care. “Our next goal is to figure out what causes variation in oxygen transport in the placenta and identify a cutoff value that would be of concern in a pregnancy, including singleton pregnancies,” she says. “Then, we can think about potential treatments to improve placental oxygen transport, and use our methods to immediately assess the success of these treatments.”

{{Future directions}}

Grant believes placental oxygen transport is a prime example of how environmental factors can modify the DNA we all inherit. Future studies will investigate how placental oxygen transport affects fetal gene expression and specific measures of brain development and organ metabolism. These studies will use a special MRI coil to improve image accuracy, developed for pregnant mothers by collaborator Larry Wald, PhD, at the Athinoula A. Martinos Center. William Barth, MD, chief of Maternal-Fetal Medicine at MGH and Chloe Zera, MD, MPH, a BWH obstetrician, have also joined the team to guide the development of novel MR imaging strategies to improve the management of pregnant mothers.

“The placenta plays a key role in fetal development and maternal health,” says David Weinberg, project lead for NIH’s Human Placenta Project, launched by the Eunice Kennedy Shriver National Institute of Child Health and Human Development.

“Understanding how it functions is essential for developing interventions to improve the health of mothers and their infants.”

Source:Science Daily

{There’s this crave among today’s women to have the best shape and posture and all that.}

New UBC study has found that just one 30-minute bout of exercise makes women feel stronger and thinner. And the positive effect lasts well beyond the activity itself, which may be good news for women concerned about their body image.

“Women, in general, have a tendency to feel negatively about their bodies,” says study senior author Kathleen Martin Ginis, professor in UBC Okanagan’s School of Health and Exercise Sciences. “This is a concern because poor body image can have harmful implications for a woman’s psychological and physical health including increased risk for low self-esteem, depression and for eating disorders. This study indicates exercise can have an immediate positive effect.”

According to the National Institutes of Health, nearly one half of North American women experience some degree of body image dissatisfaction and this has become more prevalent over the last three decades.

“We think that the feelings of strength and empowerment women achieve post exercise, stimulate an improved internal dialogue,” says Martin Ginis. “This in turn should generate positive thoughts and feelings about their bodies which may replace the all too common negative ones.”

Source:Elcrema

{Early life stress encodes lifelong susceptibility to stress through long-lasting transcriptional programming in a brain reward region implicated in mood and depression, according to a study conducted at the Icahn School of Medicine at Mount Sinai and published June 15 in the journal Science.}

The Mount Sinai study focuses on epigenetics, the study of changes in the action of genes caused not by changes in DNA code we inherit from our parents, but instead by molecules that regulate when, where, and to what degree our genetic material is activated. Such regulation derives, in part, from the function of transcription factors — specialized proteins that bind to specific DNA sequences in our genes and either encourage or shut down the expression of a given gene.

Previous studies in humans and animals have suggested that early life stress increases the risk for depression and other psychiatric syndromes, but the neurobiology linking the two has remained elusive until now.

“Our work identifies a molecular basis for stress during a sensitive developmental window that programs a mouse’s response to stress in adulthood,” says Catherine Peña, PhD, lead investigator of the study. “We discovered that disrupting maternal care of mice produces changes in levels of hundreds of genes in the VTA that primes this brain region to be in a depression-like state, even before we detect behavioral changes. Essentially, this brain region encodes a lifelong, latent susceptibility to depression that is revealed only after encountering additional stress.”

Specifically, Mount Sinai investigators identified a role for the developmental transcription factor orthodenticle homeobox 2 (Otx2) as a master regulator of these enduring gene changes. The research team showed that baby mice that were stressed in a sensitive period (from postnatal day 10-20) had suppressed Otx2 in the VTA. While Otx2 levels ultimately recovered by adulthood, the suppression had already set in motion gene alterations that lasted into adulthood, indicating that early life stress disrupts age-specific developmental programming orchestrated by Otx2.

Furthermore, the mice stressed during the early-life sensitive time period were more likely to succumb to depression-like behavior in adulthood, but only after additional adult stress. All mice acted normally before additional adult social stress, but a “second hit” of stress was more likely to trigger depression-like behavior for mice stressed during the sensitive time period.

To test the prediction that Otx2 was actually responsible for the stress sensitivity, the research team developed viral tools that were used to either increase or decrease Otx2 levels. They found that suppression of Otx2 early in life was both necessary and sufficient for increased susceptibility to adult stress.

“We anticipated that we would only be able to ameliorate or mimic the effects of early life stress by changing Otx2 levels during the early sensitive period.” says Dr. Peña. “This was true for long-lasting effects on depression-like behavior, but somewhat to our surprise we could also change stress sensitivity for short amounts of time by manipulating Otx2 in adulthood.”

While early-life critical periods have been understood for processes such as language learning, little is known about whether there are sensitive periods in childhood when stress and adversity most impacts brain development and particularly emotion-regulation systems. This study is the first to use genome-wide tools to understand how early life stress alters development of the VTA, providing new evidence for sensitive windows in emotion development.

“This mouse paradigm will be useful for understanding the molecular correlates of increased risk of depression resulting from early life stress and could pave the way to look for such sensitive windows in human studies,” says Eric J. Nestler, MD, PhD, Nash Family Professor of Neuroscience and Director of the Friedman Brain Institute at Mount Sinai and senior investigator of the study. “The ultimate translational goal of this research is to aid treatment discoveries relevant to individuals who experienced childhood stress and trauma.”

Source:Science Daily