In utero and lactational exposure to 2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD) affects bone tissue in rhesus monkeys.
Bone tissue is one of the target tissues for dioxins and dioxin-like compounds. Therefore, the aim of this study was to investigate effects of in utero and lactational exposure to 2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD), on bone tissue in rhesus monkey, the most human-like experimental model available. Pregnant rhesus monkeys (Macaca mulatta; age 4-10 years) were exposed to TCDD with a total dose of 40.5-42.0 or 405-420ng/kg bodyweight by repeated subcutaneous injections starting at gestational day 20 and followed by injections every 30 days until 90 days after delivery. At a mean age of 7 years the offspring were sacrificed and the femur bone dissected. Results from peripheral Quantitative Computed Tomography (pQCT) analyses of the metaphyseal part of the femur bones in female offspring showed significant increases in trabecular bone mineral content (BMC; +84.6%, p<0.05, F-value (F)=5.9) in the low-dose treatment group compared with the controls. In the same animals, analysis of the mid-diaphyseal part revealed increases in total BMC (+21.3%, p<0.05, F=5.2) and cortical cross-sectional area (CSA; +16.4%, p<0.01, F=7.4) compared with the controls. In males, changes in biomechanical properties indicating more fragile bone were observed. Displacement at failure were significantly increased in the male low-dose group compared to the controls (+38.0%, p<0.05, F=11). The high dose of TCDD did not induce any significant changes in bone morphology. In conclusion, in utero and lactational low-dose, but not high-dose exposure to 2,3,7,8-TCDD induced disruption of bone tissue development in rhesus monkey, a result suggesting that similar effects might occur in humans also.
Institute of Environmental Medicine, Karolinska Institutet, Nobels väg 13, Box 210, S-17177 Stockholm, Sweden.
Sanne A B
SA
Hermsen
Sune
S
Larsson
Akihiro
A
Arima
Atsunobu
A
Muneoka
Toshio
T
Ihara
Hiroshi
H
Sumida
Toshio
T
Fukusato
Shunichiro
S
Kubota
Mineo
M
Yasuda
P Monica
PM
Lind
D000818:Animals; D001696:Biomechanical Phenomena / Q000187:drug effects; D015519:Bone Density / Q000187:drug effects; D001846:Bone Development / Q000187:drug effects*; D018483:Diaphyses / Q000033:anatomy & histology / Q000187:drug effects / Q000196:embryology; D004305:Dose-Response Relationship, Drug; D005260:Female; D005269:Femur / Q000033:anatomy & histology / Q000187:drug effects / Q000196:embryology; D047109:Fetal Development / Q000187:drug effects*; D007150:Immunohistochemistry; D007774:Lactation; D008137:Longitudinal Studies; D008253:Macaca mulatta; D008297:Male; D023421:Models, Animal; D009929:Organ Size / Q000187:drug effects; D000072317:Polychlorinated Dibenzodioxins / Q000633:toxicity*; D011247:Pregnancy; D011297:Prenatal Exposure Delayed Effects; D015203:Reproducibility of Results; D014057:Tomography, X-Ray Computed
D000072317:Polychlorinated Dibenzodioxins