- Many obese women have difficulty getting pregnant. When they do, often with the help of fertility treatments, they tend to have children who are prone to obesity. Now the work in mice, the researchers identified a process of egg cells that may explain these two problems. In addition, a new drug, now diabetes in clinical trials, may offer a solution.
This is "a new idea on how obesity affects egg quality," said David Albertini, a reproductive scientist at the University of Kansas Medical Center in Kansas City, which does has not participated in the study.
obesity does not just impact the lifestyle it a person can also change the way their cells operate. high levels of fats and cholesterol can clog the machinery of a cell and interfere with its ability to build fully functional proteins. specifically, obesity stresses the endoplasmic reticulum (ER) where proteins are made and the shuttle through the cell. this process, known as ER stress name, can cause the cell to self-destruction and can occur in cells throughout the body, including the liver, pancreas and brain.
whether this stress response takes place inside egg cells so researchers led by Rebecca Robker, a cell biologist at the University of Adelaide in Australia, turned to a mouse model of obesity that faithfully reproduces what is seen in humans. The aptly named Blobby mice have a genetic mutation that causes them to overeat their way to obesity, low fat chow regular mouse.
The researchers monitored both ER stress and activity of mitochondria, the cell power generator unit, obese mouse egg cells and healthy, and how ova keeled after in vitro fertilization (IVF). When the researchers compared the gene expression profiles in obese mouse egg cells and thin, they found that the Blobby mice had significantly higher levels of genetic markers for ER stress. Criticism, Blobby eggs also had reduced mitochondrial activity compared to eggs from their meager litter mates cells.
"When we saw that the mitochondria in eggs have been damaged, we knew this was a very important and critical issue," said Robker. Mitochondria in eggs are particularly important; although both parents contribute DNA to a child, the mitochondria from the egg of the mother give rise to all the mitochondria in every cell of the body of an offspring.
The researchers found that mitochondria damaged in obese mouse eggs couldn 't properly replicate in embryos. The fetuses that developed from Blobby mouse eggs were heavier than those of lean mice, and they had less mitochondrial DNA in their livers, kidneys and hearts.
"This is important because it provides a new mechanism, a new understanding, to know how obesity can lead to a propensity own offspring to obesity," said Robker.
She and her colleagues have predicted that both the response to cellular stress and mitochondrial damage could be reversed by treating the obese mice with existing compounds. A stressed ER can flood a cell with calcium, and mitochondria, which help keep calcium levels in check within cells, can become overwhelmed and break down. Team Robker felt that the fight against the problem in the ER, the benefits would trickle down to the mitochondria. Indeed, when the researchers gave the BGP-15 obese mice ER inhibitor stress that in early clinical trials for diabetes research is already proving to be a safe and effective way to increase the mitochondria in muscle cells, eggs showed the two lower levels of cellular stress and greater mitochondrial activity. And when these eggs were fertilized and transferred into surrogate mothers, they grew increasingly overweight fetus, the team announced today online Development .
Robker team is currently testing whether the drug against diabetes will have fertility stimulate similar effects on isolated human eggs. However, she noted that weight loss and nutrition drug-place strategies may also prevent women from using in vitro fertilization. "Obese women only lose a small amount of weight and their natural fertility will often come back."
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