Variation in commercial rodent diets induces disparate molecular and physiological changes in the mouse uterus.

Although ovarian estrogen, estradiol-17beta, is a key modulator of normal reproductive functions, natural and synthetic compounds with estrogen-like activities can further influence reproductive functions. Plant-derived phytoestrogens specifically have received much attention because of associated health benefits. However, a comprehensive understanding of the beneficial and/or detrimental impacts of phytoestrogen consumption through commercial rodent diets on uterine biology and early pregnancy at the molecular level remains largely unexplored. Using multiple approaches, we demonstrate here that exposure of adult female mice to a commercial rodent diet with higher phytoestrogen levels facilitates uterine growth in the presence or absence of ovarian estrogen, alters uterine expression of estrogen-responsive genes, and advances the timing of implantation compared with a diet with lower phytoestrogen levels. The finding that variability in phytoestrogen content in commercial rodent diets, both within and between brands, influences experimental results stresses the importance of this investigation and raises caution for investigators using rodents as animal models.