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Maternal intake of high n-6 polyunsaturated fatty acid diet during pregnancy causes transgenerational increase in mammary cancer risk in mice.

ABSTRACT: Maternal and paternal high-fat (HF) diet intake before and/or during pregnancy increases mammary cancer risk in several preclinical models. We studied if maternal consumption of a HF diet that began at a time when the fetal primordial germ cells travel to the genital ridge and start differentiating into germ cells would result in a transgenerational inheritance of increased mammary cancer risk.Pregnant C57BL/6NTac mouse dams were fed either a control AIN93G or isocaloric HF diet composed of corn oil high in n-6 polyunsaturated fatty acids between gestational days 10 and 20. Offspring in subsequent F1-F3 generations were fed only the control diet.Mammary tumor incidence induced by 7,12-dimethylbenz[a]anthracene was significantly higher in F1 (p?

SUBMITTER: Nguyen NM

PROVIDER: S-EPMC5494892 | biostudies-other | 2017 Jul

REPOSITORIES: biostudies-other

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Maternal intake of high n-6 polyunsaturated fatty acid diet during pregnancy causes transgenerational increase in mammary cancer risk in mice.

Nguyen Nguyen M NM de Oliveira Andrade Fabia F Jin Lu L Zhang Xiyuan X Macon Madisa M Cruz M Idalia MI Benitez Carlos C Wehrenberg Bryan B Yin Chao C Wang Xiao X Xuan Jianhua J de Assis Sonia S Hilakivi-Clarke Leena L

Breast cancer research : BCR 20170703 1

<h4>Background</h4>Maternal and paternal high-fat (HF) diet intake before and/or during pregnancy increases mammary cancer risk in several preclinical models. We studied if maternal consumption of a HF diet that began at a time when the fetal primordial germ cells travel to the genital ridge and start differentiating into germ cells would result in a transgenerational inheritance of increased mammary cancer risk.<h4>Methods</h4>Pregnant C57BL/6NTac mouse dams were fed either a control AIN93G or ...[more]

PMID: 28673325

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Project description:A healthy diet during pregnancy is pivotal for the offspring health at birth and later in life. N-3 polyunsaturated fatty acids (n-3 PUFAs) are not endogenously produced in humans and are exclusively derived from the diet. They are pivotal for the fetus growth and neuronal development and seem beneficial in reducing the risk of cardiometabolic diseases and preventing later allergic disorders in the offspring by modulating the inflammatory immune response. In the present study, we investigated the association between maternal intakes of n-3PUFAs, profiled on maternal erythrocyte membranes at pregnancy term, and offspring DNA methylation on cord blood mononuclear cells in a sample of 118 mother-newborn pairs randomly drawn from the "Feeding fetus' low-grade inflammation and insulin-resistance" study cohort. N-3 PUFA content on erythrocyte membranes is a validated biomarker to measure objectively medium term intake of n-3 PUFAs. Based on distribution of n-3 PUFA in the whole cohort of mothers, we identified mothers with low (n-3 PUFA concentration <25th percentile), medium (n-3 PUFAs between 25th and 75th percentiles), and high n-3 PUFA content (>75th percentile). The HumanMethylation450 BeadChip (Illumina) was used for the epigenome-wide association study using the Infinium Methylation Assay. The overall DNA methylation level was not different between the three groups while there was significant difference in methylation levels at certain sites. Indeed, 8,503 sites had significantly different methylations between low and high n-3 PUFA groups, 12,716 between low and medium n-3 PUFA groups, and 18,148 between high and medium n-3 PUFA groups. We found differentially methylated genes that belong prevalently to pathways of signal transduction, metabolism, downstream signaling of G protein-coupled receptors, and gene expression. Within these pathways, we identified four differentially methylated genes, namely, MSTN, IFNA13, ATP8B3, and GABBR2, that are involved in the onset of insulin resistance and adiposity, innate immune response, phospholipid translocation across cell membranes, and mechanisms of addiction to high fat diet, alcohol, and sweet taste. In conclusion, findings of this preliminary investigation suggest that maternal intake of n-3 PUFAs during pregnancy has potential to influence the offspring DNA methylation. Validation of results in a larger cohort and investigation of biological significance and impact on the phenotype are warranted.

Dataset Information

Maternal intake of high n-6 polyunsaturated fatty acid diet during pregnancy causes transgenerational increase in mammary cancer risk in mice.

Publications

Maternal intake of high n-6 polyunsaturated fatty acid diet during pregnancy causes transgenerational increase in mammary cancer risk in mice.

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