Diethylstilbestrol (DES) has gender‐specific effects on body weight and bone development in mice

Abstract

Neonatal exposure to DES in female mice programs estrogen‐sensitive tissues, resulting in greater body weight and positive effects on bone metabolism at adulthood. Because DES can be used as a positive control when investigating effects of dietary estrogens in early life, the study objective was to determine how short‐term neonatal exposure to DES modulates body weight, as well as bone mineral, strength and microarchitecture in both male and female mice at adulthood. Male and female offspring (n=8–12 pups/treatment/gender) were randomized to DES (2 μg/d) or control (corn oil) from postnatal day 1 to 5 (subcutaneous injection) and killed at 4 months of age. Body weight was measured weekly. Bone mineral, strength and microarchitecture were measured at 4 months of age. DES treatment resulted in higher (p<0.05) body weight among females but lower (p<0.05) body weight among males at 4 months of age. Among DES‐treated females, higher (p<0.05) BMD of LV1‐LV3 was translated into stronger (p<0.05) LV2 that was more resistant to fracture with similar effects at the femur midpoint. At the spine, males had lower BMD (p<0.05) and peak load (p<0.05) suggesting an adverse effect. Microstructural analyses demonstrated that functional changes in femurs (i.e. peak load) were primarily due to changes in cortical bone. In conclusion, early exposure to DES has gender‐specific effects on body weight and bone health.