Neonatal Exposure to Daidzein, Genistein, or the Combination Modulates Bone Development in Female CD-1 Mice

Abstract

Neonatal exposure to genistein (GEN), an isoflavone abundant in soy, favorably modulates bone mineral density (BMD) and bone strength in mice at adulthood. The study objective was to determine whether early exposure to a combination of the soy isoflavones daidzein (DAI) and GEN that naturally exists in soy protein-based infant formula results in greater benefits to bone at adulthood than either treatment alone. Male and female CD-1 mice (n = 8–16 pups per group per gender) were randomized to subcutaneous injections of DAI (2 mg·kg body weight−1·d−1), GEN (5 mg·kg body weight−1·d−1), DAI+GEN (7 mg·kg body weight−1·d−1), diethylstilbesterol (DES; positive control) (2 mg·kg body weight−1·d−1), or control (CON) from postnatal d 1–5 and were studied to 4 mo of age. BMD, biomechanical bone strength, and bone microarchitecture were assessed at the femur and lumbar vertebrae (LV). Females treated with DAI, GEN, DAI+GEN, or DES had greater (P < 0.05) BMD at the LV compared with CON and vertebra in the DAI and DES group were more resistant to compression fractures. Microstructural analyses demonstrated that treatment with DAI and GEN resulted in greater (P < 0.05) trabecular connectivity and trabecular thickness, respectively, than the CON. In conclusion, neonatal exposure to DAI and/or GEN had a positive effect on the skeleton of female mice at adulthood, but, compared with individual treatments, DAI+GEN did not have a greater benefit to bone in females or males.