Diethylstilbesterol has Gender-Specific Effects on Weight Gain and Bone Development in Mice

Abstract

Neonatal exposure to diethylstilbesterol (DES) in female mice programs estrogen-sensitive tissues, resulting in greater body weight gain and positive effects on bone architecture at adulthood. Using the CD-1 mouse model, the objective of the present study was to examine how short-term neonatal exposure to DES modulates weight gain as well as bone mineral density (BMD), bone strength, and bone microarchitecture in both males and females at adulthood. Male and female offspring (n =  8–12 pups/treatment/gender) were randomized to DES (2 mg/kg bw/d) or control (corn oil) from postnatal day 1 to 5 (subcutaneous injection, once daily) and sacrificed at 4 mo of age. Body weight was measured weekly, while bone mineral, strength, and microarchitecture were measured at 4 mo of age. DES treatment resulted in significantly higher body weight in females but lower weight in males at 4 mo of age. In DES-treated females, markedly higher BMD of lumbar vertebrae (LV1–LV3) was translated into significantly stronger LV2 that was more resistant to fracture; similar effects were observed at the femur midpoint. At the spine, males had a markedly lower BMD and peak load, suggesting an adverse effect. Microstructural analyses demonstrated that functional changes in femurs, i.e., peak load, were primarily due to modulation of cortical bone. In conclusion, neonatal exposure to DES exerted gender-specific effects on body weight gain and bone health.

Acknowledgements

W. Ward holds a Future Leader Award from the International Life Sciences Institute North America (ILSI N.A.), and this work was supported, in part, by a grant from the ILSI N.A. The opinions expressed herein are those of the authors and do not necessarily represent the views of ILSI N.A.