Effect of neonatal exposure to diethylstilbestrol and tamoxifen on pelvis and femur in male mice

Fukazawa, Yugo; Nobata, Sigenori; Katoh, Miho; Tanaka, Masami; Kobayashi, Sinji; Ohta, Yasuhiko; Hayashi, Yokichi; Iguchi, Taisen

doi:10.1002/(sici)1097-0185(199603)244:3<416::aid-ar12>3.0.co;2-s

Cited by 15 publications

(2 citation statements)

References 30 publications

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“…High-dose DES (0.5 to 3 mg/kg/day) administered on Postnatal Days 1-5 resulted in altered adult femur length and strength [22][23][24][25][26]. Exposure to other xenoestrogens has been reported to alter long bone parameters.…”

Section: Introductionmentioning

confidence: 99%

Developmental Exposure to Xenoestrogens at Low Doses Alters Femur Length and Tensile Strength in Adult Mice1

Pelch

Carleton

Phillips

et al. 2012

Biology of Reproduction

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Developmental exposure to high doses of the synthetic xenoestrogen diethylstilbestrol (DES) has been reported to alter femur length and strength in adult mice. However, it is not known if developmental exposure to low, environmentally relevant doses of xenoestrogens alters adult bone geometry and strength. In this study we investigated the effects of developmental exposure to low doses of DES, bisphenol A (BPA), or ethinyl estradiol (EE(2)) on bone geometry and torsional strength. C57BL/6 mice were exposed to DES, 0.1 μg/kg/day, BPA, 10 μg/kg/day, EE(2), 0.01, 0.1, or 1.0 μg/kg/day, or vehicle from Gestation Day 11 to Postnatal Day 12 via a mini-osmotic pump in the dam. Developmental Xenoestrogen exposure altered femoral geometry and strength, assessed in adulthood by micro-computed tomography and torsional strength analysis, respectively. Low-dose EE(2), DES, or BPA increased adult femur length. Exposure to the highest dose of EE(2) did not alter femur length, resulting in a nonmonotonic dose response. Exposure to EE(2) and DES but not BPA decreased tensile strength. The combined effect of increased femur length and decreased tensile strength resulted in a trend toward decreased torsional ultimate strength and energy to failure. Taken together, these results suggest that exposure to developmental exposure to environmentally relevant levels of xenoestrogens may negatively impact bone length and strength in adulthood.

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Section: Introductionmentioning

confidence: 99%

Developmental Exposure to Xenoestrogens at Low Doses Alters Femur Length and Tensile Strength in Adult Mice1

Pelch

Carleton

Phillips

et al. 2012

Biology of Reproduction

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“…Tamoxifen acts directly on the neonatal mouse pubis and os penis to inhibit its ossification Iguchi, 1992;Iguchi and Ohta, 1996). Neonatal DES exposure induced persistent reduction of calcium and phosphorus in the pelvis and femur in aged mice (Fukazawa et al, 1996), indicating that neonatal DES and tamoxifen exposure result in permanent changes in bone tissue in mice.…”

Section: Abnormalities In Skeletal Tissue Andmentioning

confidence: 99%

Endocrine Disruption and Developmental Abnormalities of Female Reproduction

Iguchi

Satō

2000

Am Zool

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The developing organism is particularly sensitive to exposure to estrogenic chemicals during a critical period in the induction of longterm changes in female reproductive organs, and persistent molecular alterations induced by the perinatal estrogenic agents. The perinatal mouse model can be utilized as an indicator of possible longterm consequences of exposure to exogenous estrogenic compounds including environmental endocrine disruptors. Attention should be paid to abnormalities in female genital organs exposed to estrogenic endocrine disruptors during fetal and early postnatal development in mammals including humans.

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Early estrogen exposure induces abnormal development of Fundulus heteroclitus

et al. 2002

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Many chemicals released into the environment exhibit estrogenic activity, having the potential to disrupt development and the functioning of the endocrine system. In order to establish a model system to study the effects of such environmental chemicals on aquatic animals, we examined the effects of a natural estrogen, 17 beta-estradiol (E(2)), on early development of Fundulus heteroclitus. Embryos of F. heteroclitus were reared in seawater containing 10(-10), 10(-8), and 10(-6) M E(2) throughout the experiment. Hatching and survival rates decreased in a dose-dependent manner, and fry treated with 10(-6) M E(2) and 10(-8) M E(2) were dead by two weeks and 12 weeks after hatching, respectively. More than 85% of fry treated with 10(-8) M E(2) showed malformations: i.e., eye extrusion, crooked vertebral column, faded lateral-stripe pattern eight weeks after hatching. Body weight and head and body lengths were significantly reduced in E(2)-treated fry when compared to controls. Ossification was not completed in vertebrae, cranial bones, and other bones in fry treated with 10(-8) M E(2) even 12 weeks after hatching. Sex ratio of control fry was 57% male and 43% female, whereas fry treated with 10(-8) M E(2) were 100% female eight weeks after hatching. The present results demonstrate that exogenous estrogen induced death of embryos and fry, malformations, sex reversal, and incomplete ossification of vertebrae and cranial bones, which would result in shorter body and head lengths and in malformed vertebrae leading to a hunchback condition.

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Effect of neonatal exposure to diethylstilbestrol and tamoxifen on pelvis and femur in male mice

Cited by 15 publications

References 30 publications

Developmental Exposure to Xenoestrogens at Low Doses Alters Femur Length and Tensile Strength in Adult Mice1

Developmental Exposure to Xenoestrogens at Low Doses Alters Femur Length and Tensile Strength in Adult Mice1

Endocrine Disruption and Developmental Abnormalities of Female Reproduction

Early estrogen exposure induces abnormal development of Fundulus heteroclitus

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