# Impact of Dietary Isoflavones in Standard Chow on Reproductive Development in Juvenile and Adult Female Mice with Different Metabolic Phenotypes

## TL;DR

This study shows how dietary isoflavones and metabolic traits affect reproductive development in female mice, with notable effects on sexual maturation and gestation.

## Contribution

The study is the first to combine the effects of dietary isoflavones and metabolic phenotypes on reproductive development in mice.

## Key findings

- Dietary isoflavones caused earlier sexual maturation in juvenile mice, depending on their genetic/metabolic group.
- Gestation length was affected by isoflavone dose in all genetic groups, and pregnancy rates were altered in obese mice.
- Plasma isoflavone levels varied significantly between standard chows with similar macronutrient profiles.

## Abstract

Two factors influencing female reproduction have been repeatedly studied in different animal species and humans, namely, 1. secondary plant compounds, especially phytoestrogens (mainly isoflavones (IFs)), and 2. the physical constitution/metabolic phenotype (e.g., obesity). So far, these research results have only been considered separately. In this study, we investigated the influence on reproduction of both phytochemicals, mainly dietary IFs, and the metabolic phenotype represented by three mouse models considered as three distinct genetic groups (a control group, a mouse model with high metabolic activity, and a mouse line with obese body weight). The IF content in different investigated standard chows with similar macronutrient profiles varied significantly (p < 0.005), leading to high mean total plasma IF levels of up to 5.8 µmol/L in juvenile and 6.7 µmol/L in adult female mice. Reproductive performance was only slightly affected; only an IF dose-dependent effect on gestation length was observed in all genetic groups, as well as an effect on pregnancy rate in obese mice. Dietary IF exposure, however, caused earlier onset of vaginal opening by 4–10 days in juvenile mice (p < 0.05), dependent on the genetic group, resulting in a slight acceleration of sexual maturation in the already precocious obese model and to a strong earlier maturation in the otherwise late-maturing sporty model, bred for high treadmill performance. Therefore, our results may help to draw the missing line between the effect of dietary secondary plant constituents, such as IFs, and metabolic phenotype on sexual development.