Maternal B vitamin supplementation from preconception through weaning suppresses intestinal tumorigenesis in Apc1638N mouse offspring

Eric D Ciappio ¹, Zhenhua Liu , Ryan S Brooks

⁰Vitamins and Carcinogenesis Laboratory, Jean Mayer USDA Human Nutrition Research Center on Aging at Tufts University, Boston, MA 02111, USA.

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June 11, 2011

View abstract on PubMed

Summary

Maternal B vitamin supplementation during pregnancy and nursing suppressed intestinal tumor development in offspring. Conversely, deficiency promoted tumor growth and invasiveness, highlighting the critical role of B vitamins in early development.

Area Of Science

Nutritional science
Developmental biology
Cancer research

Background

Folate intake influences colorectal cancer development, with timing being crucial.
Understanding the impact of B vitamin availability during critical developmental windows is essential for cancer prevention strategies.

Purpose Of The Study

To investigate how altering folate and B vitamin availability during in-utero development and suckling affects intestinal tumorigenesis.
To determine the long-term effects of maternal B vitamin status on offspring's susceptibility to intestinal tumors.

Main Methods

Wildtype female mice were fed varying diets (deficient, replete, supplemented) for 4 weeks pre-mating and throughout gestation and lactation.
Apc(1638N) offspring were maintained on replete diets post-weaning until 8 months of age.
Tumor incidence, invasiveness, gene expression (Apc, Sfrp1, Wif1, Wnt5a), promoter methylation, and beta-catenin protein levels were assessed.

Main Results

Offspring of supplemented mothers showed significantly lower tumor incidence (21%) compared to replete (59%) and deficient (55%) mothers.
Tumors in offspring of deficient dams were more likely to be invasive.
Decreased maternal B vitamin intake correlated with reduced expression of Wnt pathway negative regulators and elevated beta-catenin in offspring.

Conclusions

Maternal B vitamin deficiency during development leads to Wnt pathway de-repression, promoting intestinal tumorigenesis in offspring.
Maternal B vitamin supplementation demonstrates a protective effect, suppressing intestinal tumor development.
These findings underscore the critical role of maternal nutrition, specifically B vitamins, in modulating offspring's cancer risk.

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