Lead exposure in mothers can affect future generations

 

Mothers with high levels of lead in their blood not only affect the fetal cells of their unborn children, but also their grandchildren. Credit: © tatyana_k / Fotolia A team of researchers at Wayne State University have discovered that mothers with high levels of lead in their blood not only affect the fetal cells of their unborn children, but also their grandchildren. Their study, Multigenerational epigenetic inheritance in humans: DNA methylation changes associated with maternal exposure to lead can be transmitted to the grandchildren, was published online this week in Scientific Reports. It's a known fact that babies in the womb can be affected by low levels of lead exposure. If a pregnant woman is exposed to lead, the lead passes through the placenta into the baby's developing bones and other organs. Pregnant women with a past exposure to lead can also affect the unborn child's brain, causing developmental problems later in life. Previous research studies have suggested that exposure to heavy metal toxicants can influence a person's global DNA methylation profile. In the recent Wayne State study led by Douglas Ruden, Ph.D., professor in the Department of Obstetrics & Gynecology and the Institute of Environmental Health Sciences, director of epigenomics, and program leader in the Center for Urban Responses to Environmental Stressors, he and his research team revealed that lead exposure can cause specific changes in DNA methylation, which can be detected in dried blood spots beyond one generation. The neonatal blood spots from both the mothers and children in this study were obtained from the Michigan Neonatal Biobank, a unique resource that has most of the neonatal dried blood spots from children born in Michigan since 1984. According to Ruden, epigenetic effects of environmental exposures beyond one generation have not yet been demonstrated in humans prior to this study. He and his team tested the hypothesis that human fetal germ cell exposure to environmental toxins causes epigenetic changes in the newborn blood from a grandchild of an exposed pregnant woman. "Our results suggest that lead exposure during pregnancy affects the DNA methylation status of the fetal germ cells, which leads to altered DNA methylation in grandchildren's neonatal dried blood spots," said Ruden. "This is the first demonstration that an environmental exposure in pregnant mothers can have an epigenetic effect on the DNA methylation pattern in the grandchildren." The research team stated that this novel, two-generational study design might be able to identify the genes that may serve as possible candidate biomarkers for future transgenerational risk assessment studies. "Our pilot study provides indirect evidence that lead exposure in women during childbirth can affect the locus-specific DNA methylation status of grandchildren," said Ruden. "However, the altered DNA methylation profiles of the grandchildren's blood are apparently normalized during postnatal development. Also, fetal germline exposure to lead apparently has different epigenetic consequences than acute childhood exposure." Story Source: The above post is reprinted from materials provided by Wayne State University - Office of the Vice President for Research. Note: Materials may be edited for content and length. Journal Reference: Arko Sen, Nicole Heredia, Marie-Claude Senut, Susan Land, Kurt Hollocher, Xiangyi Lu, Mary O. Dereski, Douglas M. Ruden. Multigenerational epigenetic inheritance in humans: DNA methylation changes associated with maternal exposure to lead can be transmitted to the grandchildren. Scientific Reports, 2015; 5: 14466 DOI: 10.1038/srep14466   http://www.sciencedaily.com/releases/2015/10/151002191739.htm

High-fat diet, obesity during pregnancy harms stem cells in developing fetus

 

Physician-scientists at OHSU Doernbecher Children's Hospital reveal a high-fat diet and obesity during pregnancy compromise the blood-forming, or hematopoietic, stem cell system in the fetal liver responsible for creating and sustaining lifelong blood and immune system function. The life-long burden of a western-style diet on the heart and circulatory system have long been appreciated. However, prior to this study, no one had considered whether the developing blood stem cells might be similarly vulnerable to prenatal high-fat diet and/or maternal obesity. The findings are published in the journal Molecular Metabolism. "Our results offer a model for testing whether the effects of a high-fat diet and obesity can be repaired through dietary intervention, a key question when extrapolating this data to human populations," said Daniel L. Marks, M.D., Ph.D., co-investigator and professor of pediatric endocrinology in the OHSU School of Medicine and Papé Family Pediatric Research Institute at OHSU Doernbecher Children's Hospital. Several years ago, Marks and colleagues developed a mouse model that closely mimics the high-fat, high-simple-sugar diet currently consumed by many young women of childbearing age. Their subsequent research demonstrated that maternal overnutrition in mice significantly reduced the size of the fetal liver. Armed with this information, Marks partnered with another stem cell expert, Peter Kurre, M.D., co-investigator on the current study and professor of pediatric oncology in the OHSU School of Medicine and the Papé Family Pediatric Research Institute at OHSU Doernbecher Children's Hospital. Together, they discovered that the complex changes that occur as a result of maternal high-fat diet and obesity put significant constraints on the growth and expansion of blood stem cells in the fetal liver, which ultimately compromises the developing immune system. "In light of the spreading western-style, high-fat diet and accompanying obesity epidemic, this study highlights the need to better understand the previous unrecognized susceptibility of the stem and progenitor cell system," Kurre said. "These findings may provide broad context for the rise in immune disease and allergic disposition in children." Story Source: The above story is based on materials provided by Oregon Health & Science University. Note: Materials may be edited for content and length. Journal Reference: Ashley N. Kamimae-Lanning, Stephanie M. Krasnow, Natalya A. Goloviznina, Xinxia Zhu, Quinn R. Roth-Carter, Peter R. Levasseur, Sophia Jeng, Shannon K. McWeeney, Peter Kurre, Daniel L. Marks. Maternal high-fat diet and obesity compromise fetal hematopoiesis. Molecular Metabolism, 2014; DOI: 10.1016/j.molmet.2014.11.001

Taking antibiotics during pregnancy increases risk for child becoming obese

 

November 18, 2014

Columbia University's Mailman School of Public Health

A study just released by Columbia University's Mailman School of Public Health found that children who were exposed to antibiotics in the second or third trimester of pregnancy had a higher risk of childhood obesity at age 7. The research also showed that for mothers who delivered their babies by a cesarean section, whether elective or non-elective, there was a higher risk for obesity in their offspring.

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A study just released by Columbia University's Mailman School of Public Health found that children who were exposed to antibiotics in the second or third trimester of pregnancy had a higher risk of childhood obesity at age 7. The research also showed that for mothers who delivered their babies by a Caesarean section, whether elective or non-elective, there was a higher risk for obesity in their offspring. Study findings are published online in the International Journal of Obesity.

Although previous studies have shown that antibiotics administered early in life may be associated with increased risk of obesity in childhood, this is the first study reporting that maternal antibiotic use in the second or third trimester of pregnancy increases the risk of offspring obesity. Antibiotics affect microbes in the mother and may enter fetal circulation via the placenta. Researchers are beginning to understand that the bacteria that normally inhabit our colon have important roles in maintaining our health and imbalances in these bacterial populations can cause a variety of illnesses. Disturbances in the normal, transmission of bacteria from the mother to the child are thought to place the child at risk for several health conditions, including obesity.

The study is based on data of healthy, non-smoking, pregnant women who were recruited for the Northern Manhattan Mothers and Children Study from prenatal clinics at New York-Presbyterian Hospital and Harlem Hospital Center between 1998 and 2006. Of 727 mothers enrolled in the study, 436 mothers and their children were followed until 7 years of age. Of these 436 children, 16 percent had mothers who used antibiotics in the second or trimester. This work is part of the Columbia Center for Children's Environmental Health's efforts to understand how to promote healthy growth and development through out childhood and adolescence.

The children exposed to antibiotics in this timeframe had an 84-percent higher risk of obesity, compared with children who were not exposed.

"Our findings on prenatal antibiotics and risk for offspring obesity are novel, and thus warrant replication in other prospective cohort studies," said Noel Mueller, PhD, postdoctoral research fellow at Columbia University's Mailman School of Public Health and Institute of Human Nutrition. "If these findings hold up, they suggest new mechanisms through which childhood growth trajectories are influenced at the earliest stages of development. Our findings should not discourage antibiotic use when they are medically needed, but it is important to recognize that antibiotics are currently overprescribed."

Independent of prenatal antibiotic usage, delivery by Caesarean section was also associated with a 46-percent higher risk of childhood obesity. The researchers controlled for maternal age, ethnicity, birth weight, sex, breastfeeding in the first year, and gestational antibiotics or delivery mode.

"Our findings are consistent with a series of papers that looked at data on Caesarean section. While earlier studies suggested that childhood outcomes differ by whether the Caesarean section was elective or non-elective, we did not observe such evidence," said Andrew Rundle, DrPH, associate professor of Epidemiology at the Mailman School of Public Health. "Thus, our findings provide new evidence in support of the hypothesis that Caesarean section independently contributes to the risk of childhood obesity."

Similar to antibiotic use during pregnancy, Caesarean section birth is thought to reduce the normal transmission of bacteria from the mother to the child and to disturb the balance of bacteria in the child. "Strategies to reduce medically unnecessary C-sections and to provide the infant with health promoting bacteria after C-section need to be researched," noted Dr. Mueller.

"Further research is needed on how mode of delivery, antibiotic use during pregnancy and other factors influence the establishment of the ecosystem of bacteria that inhabit each of us," said Dr. Rundle. "This research will help us understand how to create an early platform to support the healthy growth and development of children."

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Story Source:

The above story is based on materials provided by Columbia University's Mailman School of Public Health. Note: Materials may be edited for content and length.

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Journal Reference:

1. N T Mueller, R Whyatt, L Hoepner, S Oberfield, M G Dominguez-Bello, E M Widen, A Hassoun, F Perera, A Rundle. Prenatal exposure to antibiotics, cesarean section and risk of childhood obesity. International Journal of Obesity, 2014; DOI: 10.1038/ijo.2014.180

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Antidepressant use during pregnancy may lead to childhood obesity, diabetes

 

June 21, 2014

McMaster University

Maternal use of a class of antidepressants called selective serotonin reuptake inhibitors, or SSRIs, resulted in increased fat accumulation and inflammation in the liver of the adult offspring, researchers have demonstrated for the first time in an animal model. This raises new concerns about the long-term metabolic complications in children born to women who take SSRI antidepressants during pregnancy.

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Women who take antidepressants during pregnancy may be unknowingly predisposing their infants to type 2 diabetes and obesity later in life, according to new research from McMaster University.

The study finds a correlation between the use of the medication fluoxetine during pregnancy and an increased risk of obesity and diabetes in children.

Currently, up to 20 per cent of woman in the United States and approximately seven per cent of Canadian women are prescribed an antidepressant during pregnancy.

"Obesity and Type 2 diabetes in children is on the rise and there is the argument that it is related to lifestyle and availability of high calorie foods and reduced physical activity, but our study has found that maternal antidepressant use may also be a contributing factor to the obesity and diabetes epidemic," said the study's senior investigator Alison Holloway, associate professor of obstetrics and gynecology at McMaster University.

Previous studies have found that pregnant women are particularly vulnerable to depression and it is estimated that up to one in five pregnant women have symptoms of depression during pregnancy.

"While it is known that these drugs can increase the risk of obesity in adults, it is unknown whether a woman's antidepressant use during pregnancy increases the risk of metabolic disturbances in her children," Holloway says, adding the goal of their project was to determine whether maternal exposure to a commonly used antidepressant is related to the development of fatty liver, an outcome commonly seen with obesity, in the offspring.

"We have demonstrated for the first time in an animal model that maternal use of a class of antidepressants called selective serotonin reuptake inhibitors, or SSRIs, resulted in increased fat accumulation and inflammation in the liver of the adult offspring, raising new concerns about the long-term metabolic complications in children born to women who take SSRI antidepressants during pregnancy," says PhD student Nicole De Long, who presented this research on June 22nd at the joint meeting of the International Society of Endocrinology and The Endocrine Society.

Their study does not suggest women should avoid taking antidepressants during pregnancy, only that there may be risks associated with antidepressants that haven't been previously identified, Holloway says.

"The benefit of the study is it may help in the identification of a high-risk group of children who may require specific interventions to prevent obesity and type 2 diabetes later in life," she says.

The next stage of their research will be to understand the mechanistic pathways behind why these drugs pose a risk. "If we can understand how the antidepressant causes adverse metabolic outcomes in the offspring than we can design therapeutic strategies to prevent the damage while allowing women who require these drugs to be treated but reduce the potential harm to the offspring.