2024-01-25 23:56:34
A study explains why a protein-deficient diet during pregnancy increases the risk of prostate cancer in offspring
Time: January 26, 2024
Source: AAAS
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In experiments on mice, researchers at São Paulo State University found changes in the expression of more than 700 genes in the offspring. One of these genes is known to be associated with prostate cancer.
Experiments on mice by researchers at the State University of São Paulo (UNESP) help understand why the offspring of women who are malnourished during pregnancy have a higher risk of developing prostate cancer as adults.
In the first study, conducted with support from FAPESP, researchers have found that changes in gene expression may be associated with hormone imbalances and increased risk of prostate cancer in the offspring of rats.
“A lack of protein during pregnancy and lactation is known to dysregulate the molecular pathways involved in normal prostate development, leading to impaired prostate growth in young infants. “We have now found that during the embryonic stage and in the first two years of life, protein levels A low diet changes the expression of more than 700 genes in offspring, including the ABCG1 gene linked to prostate cancer,” said study leader Luis Antônio Justulin Junior, professor at the Institute of Biosciences in Botucatu (IBB-UNESP).
In another study, the release of a specific type of RNA (microRNA-206) was associated with early increases in the female sex hormone estrogen, a distinct characteristic of offspring of female rats fed a protein-restricted diet during gestation and lactation. , is also a factor in increased prostate cancer risk.
“The findings once again show that diet and everything else during the earliest stages of development determine the health and disease trajectories of offspring. They make an important contribution to our understanding of the first 1,000 days of life, a period that encompasses pregnancy, lactation and infancy. period until the baby’s second birthday.”
lifetime impact
Research into the links between maternal care and offspring development has made significant progress in recent decades, particularly in an area known as the developmental origins of health and disease. There is good evidence that insufficient gene-environment interactions during the embryonic stage and the first two years of life may be a key factor in increasing the lifetime risk of non-communicable chronic diseases such as cancer, diabetes, chronic respiratory disease and cardiovascular disease.
Jewish men who suffered starvation and the horrors of the Holocaust in early childhood had a much higher than normal risk of developing prostate cancer, according to a 2009 international study. The study of how behavioral and environmental factors, such as maternal malnutrition, affect gene expression is called epigenetics. Epigenetic changes are reversible and do not alter the DNA sequence by causing mutations. They can change the way an organism reads DNA sequences and alter the expression of genes in future generations. New gene expression patterns can be passed on to future generations.
The UNESP study explored the cellular mechanisms involved in this process through experiments in rats. Some of the results were published in an article in the journal Scientific Reports. The authors describe global expression profiles of microRNAs and messenger RNAs, highlighting molecular alterations associated with increased prostate cancer risk. It is worth recalling that microRNA regulates the expression of messenger RNA, which plays a crucial role in protein synthesis, through epigenetic mechanisms. Therefore, microRNAs are important factors in gene expression.
After generating RNA sequences and analyzing them using bioinformatics, the researchers concluded that prostate cancer in maternally malnourished offspring and in aged rats exposed to intrauterine protein restriction may be due to early-stage miR-206 and Dysregulation of its target gene, PLG, may occur in response to abnormally high levels of estrogen during pregnancy.
“We also found that miR-206 regulates the expression of estrogen receptor alpha (ERα), which is thought to be associated with increased risk of prostate cancer in adulthood.”
In addition to differences in glandular development and growth, hormonal imbalances are observed early in life. “These animals have higher estrogen levels, which rise more as they age, while androgen levels fall.” This hormone imbalance has been linked to the development of prostate cancer in humans. “
The article, published in Scientific Reports, won an award at Associa’s first conference in Brazil. 1>
target gene
In a second article published in the journal Molecular and Cellular Endocrinology, the team describes changes in multiple genes in the prostates of rat offspring that were identified through sequencing. Sequencing works by measuring the expression of several genes to obtain the transcriptome, the complete set of molecules present in the cells of a tissue sample.
When the researchers looked for correlations between the findings and a human prostate cancer database, they discovered that one of the altered genes was a potential “gene” linked to a disorder of prostate development that has lasting effects that may Increased risk of cancer.
“We found that changes in gene expression profiles can persist throughout the life of rats, predisposing them to prostate cancer as they age. Curiously, we found that maternally malnourished offspring in both young and old rats and in human prostate cancer patients, molecular markers are frequently deregulated. The data suggest that maternal malnutrition is a key environmental factor in the development of prostate cancer in offspring rats.”
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