title: Effect of in utero exposure to diethylstilbestrol on lumbar and femoral bone, articular cartilage, and the intervertebral disc in male and female adult mice progeny with and without swimming exercise.
abstract: BACKGROUND
  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 μg/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 by using a PIXImus Bone Densitometer System. Intervertebral disc proteoglycan was measured with the DMMB assay. Histologic analysis of proteoglycan for IVD and articular cartilage was performed with safranin O staining, and degeneration parameters were scored.
  
  
  RESULTS
  The lumbar BMC was significantly increased in female swimmers at both the highest and lowest dose of DES, whereas the femoral BMC was increased only at the highest. The males, conversely, 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, whereas the male counterpart showed a decreased BA for femoral bone. The TBA showed a similar pattern. Proteoglycan analysis of lumbar IVDs showed a decrease at the lowest doses but a significant increase at the highest doses for both males and females. Histologic examination showed morphologic 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.
authors.affiliation: Lady Davis Institute for Medical Research, Sir Mortimer B, Davis-Jewish General Hospital, 3755 Chemin Cote Ste Catherine, Montréal, Quebec H3T 1E2, Canada.
authors.forename: Sora Al
authors.initials: SA
authors.lastname: Rowas
authors.forename: Rami
authors.initials: R
authors.lastname: Haddad
authors.forename: Rahul
authors.initials: R
authors.lastname: Gawri
authors.forename: Abdul Aziz
authors.initials: AA
authors.lastname: Al Ma'awi
authors.forename: Lorraine E
authors.initials: LE
authors.lastname: Chalifour
authors.forename: John
authors.initials: J
authors.lastname: Antoniou
authors.forename: Fackson
authors.initials: F
authors.lastname: Mwale
mesh_terms: D000284:Administration, Oral; D000818:Animals; D015519:Bone Density / Q000187:drug effects; D001842:Bone and Bones / Q000187:drug effects* / Q000378:metabolism / Q000473:pathology; D002358:Cartilage, Articular / Q000187:drug effects* / Q000378:metabolism / Q000473:pathology; D004054:Diethylstilbestrol / Q000633:toxicity*; D004305:Dose-Response Relationship, Drug; D004968:Estrogens, Non-Steroidal / Q000633:toxicity; D005260:Female; D005269:Femur / Q000187:drug effects / Q000378:metabolism / Q000473:pathology; D007403:Intervertebral Disc / Q000187:drug effects / Q000378:metabolism / Q000473:pathology; D008159:Lumbar Vertebrae / Q000187:drug effects / Q000378:metabolism / Q000473:pathology; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D011247:Pregnancy; D011297:Prenatal Exposure Delayed Effects / Q000139:chemically induced / Q000503:physiopathology*; D011509:Proteoglycans / Q000378:metabolism; D013550:Swimming / Q000502:physiology*; D013997:Time Factors; D055114:X-Ray Microtomography
chemical_list: D004968:Estrogens, Non-Steroidal; D011509:Proteoglycans; D004054:Diethylstilbestrol