Research article
Effect of in utero exposure to diethystilbesterol on lumbar and femoral bone, articular cartilage and the intervertebral disc in male and female adult mice progeny with and without swimming exercise
Arthritis Research & Therapy 2012, 14:R17 doi:10.1186/ar3696
Published: 23 January 2012Abstract (provisional)
Introduction
Developmental exposure to estrogens has been shown to affect the musculoskeletal system. Furthermore, recent studies have shown that environmental exposure to estrogen-like compounds is much higher than originally anticipated. The aim of this study was to determine the effects of diethylstilbestrol (DES), a well-known estrogen agonist, on articular cartilage, intervertebral disc (IVD), and bone phenotype.
Methods
C57Bl/6 pregnant mice were dosed orally with vehicle (peanut oil) or 0.1, 1.0 and 10 ug/kg/day of DES on gestational days 11 to 14. Male and female pups were allowed to mature without further treatment until 3 months of age, when swim and sedentary groups were formed. After euthanasia, bone mineral density (BMD), bone mineral content (BMC), bone area (BA), and trabecular bone area (TBA) of the lumbar vertebrae and femur were measured using a PIXImus Bone Densitometer System (GE Medical Systems). Intervertebral disc (IVD) proteoglycan was measured by the DMMB assay. Histological analysis of proteoglycan for IVD and articular cartilage was performed with Safranin O staining and degeneration parameters scored.
Results
The lumbar BMC, was significantly increased in female swims at both the highest and lowest dose of DES, while the femoral BMC was only increased at the highest. The males, on the other hand, showed a decreased BMC at the highest dose of DES for both lumbar and femoral bone. The female swim group had an increased BA at the highest dose of DES while the male counterpart showed a decreased BA for femoral bone. The TBA showed a similar pattern. Proteoglycan analysis of lumbar IVD's showed a decrease at the lowest doses but a significant increase at the highest doses for both males and females. Histology showed morphological changes of the IVD and articular cartilage for all doses of DES.
Conclusions
DES significantly affected the musculoskeletal system of adult mice. Results suggest that environmental estrogen contaminants can have a detrimental effect on the developmental lumbar bone growth and mineralization in mice. Further studies measuring the impact of environmental estrogen mimics, such as bisphenol A, are then warranted.