Poor Diet During Pregnancy Raises Risk of Prostate Cancer in Kids

Researchers at São Paulo State University (UNESP) in Brazil conducted mouse experiments to better understand why the descendants of women who were malnourished during pregnancy have a higher risk of prostate cancer as adults.

In the first study, published in Scientific Reports, researchers discovered changes in gene expression that may have been linked to the hormone imbalance identified in the rats’ pups and the increased risk of prostate cancer.

“Lack of protein during gestation and lactation deregulates the molecular pathways involved in normal development of the prostate, leading to impairment of its growth in young offspring. This was already known. We’ve now discovered that a protein-poor diet during the embryo stage and the first two years after birth alters the expression of more than 700 genes in offspring, including the gene ABCG1, which is associated with prostate cancer,” said Luis Antônio Justulin Junior, who directs the research and is a professor at the Botucatu Institute of Biosciences (IBB-UNESP).

In a second study published in Molecular and Cellular Endocrinology, deregulation of a specific type of RNA (microRNA-206) was linked to an early-life increase in the hormone estrogen, a prominent trait in the offspring of female rats fed a protein-restricted diet during gestation and lactation, and a factor associated with an increased risk of prostate cancer.

Justulin said, “The results showed once again how much diet and everything else that happens in the initial stages of development determine the trajectory of health and disease in offspring. They were a key contribution to our understanding of the first 1,000 days of life, the period comprising pregnancy, breastfeeding and infancy until the baby’s second birthday”.

Lifelong influence

In recent decades, there has been a tremendous increase in research into the relationships between mother health and offspring development, particularly in the field of developmental origins of health and disease. There is ample evidence that inadequate gene-environment interaction during the embryonic stage and the first two years after birth can significantly increase the lifelong risk of noncommunicable chronic diseases (NCCDs) such as cancer, diabetes, chronic respiratory disorders, and cardiovascular disease.

According to a 2009 worldwide study, Jewish males exposed to poverty and the horrors of the Holocaust had a significantly higher incidence of prostate cancer than the general population. Epigenetics is the study of how behavioral and environmental variables, such as maternal starvation, impact gene expression. Epigenetic modifications are reversible and do not alter DNA sequences by introducing mutations. They can influence how an organism reads a DNA sequence and how genes are expressed in offspring. Future generations can inherit novel gene expression patterns.

UNESP’s research focused on the cellular pathways involved in this process using rat trials. Some of the findings are reported in a Scientific Reports paper. The authors discuss the worldwide expression profile of microRNA and messenger RNA, focusing on molecular changes linked with an increased risk of prostate cancer. It is worth noting that microRNAs regulate messenger RNA expression through epigenetic processes, and messenger RNA is essential for protein synthesis. Thus, microRNAs play a significant role in gene expression.

More information: Luiz M. F. Portela et al, Early-life origin of prostate cancer through deregulation of miR-206 networks in maternally malnourished offspring rats, Scientific Reports (2023). DOI: 10.1038/s41598-023-46068-1

Ana CL. Camargo et al, Deregulation of ABCG1 early in life contributes to prostate carcinogenesis in maternally malnourished offspring rats, Molecular and Cellular Endocrinology (2023). DOI: 10.1016/j.mce.2023.112102

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