Alterations in estrogen levels during development affects the skeleton: use of an animal model


Exposure to estrogens during various stages of development has been shown to irreversibly influence responsive target organs. The recent finding of the presence of estrogen receptor in both osteoblasts and osteoclasts has suggested a direct role of steroid hormones on bone tissue. Furthermore, estrogens have important effects on bone turnover in both humans and experimental animal models. Thus,  this tissue is now regarded as a specific estrogen target tissue.

Alterations in estrogen levels during development affects the skeleton: use of an animal model, Environmental Health Perspectives, NCBI PubMed PMC1518867, 1995 Oct.

To investigate whether a short-term developmental exposure to estrogens can influence bone tissue, we have injected female mice with diethylstilbestrol (DES) from day 1 through day 5 of life. Additionally, a group of pregnant female mice were injected with different doses of DES from day 9 through 16 of pregnancy. Mice were then weaned at 21 days of age, and effects on bone tissue of the female mice were evaluated in adulthood (7-12 months of age).

These short-term treatments did not affect body weight of exposed mice. However, a dose-dependent increase in bone mass, both in the trabecular and compact compartments, was observed in the DES-exposed female offspring. Furthermore, femurs from DES-exposed females were shorter than femurs from controls. A normal skeletal mineralization accompanied these changes in the bone tissue. In fact, a parallel increase in total calcium content of the skeleton was found in concomitance with the increase in bone mass. Estrogen treatment induced an increase in the amount of mineralized skeleton when compared to untreated controls.

In summary, this report shows that alterations of estrogen levels during development can influence the early phases of bone tissue development inducing permanent changes in the skeleton. These changes appear to be related to bone cell programming in early phases of life.


At the present time our result cannot either indicate or rule out any potential teratogenic or carcinogenic effect of the early exposure to DES in the skeleton of these female mice. It is interesting to know, however, that there have been a few self reports of spondylolisthesis in women exposed prenatally to DES (23). Thus, it may be clinically important to further investigate the possibility that exposure of the human population to exogenous estrogens could permanently affect skeletal tissue. In particular, it will be clinically relevent to evaluate whether low or high doses of these steroids could affect the skeleton in different manner, for instance increasing peak bone density or inducing skeletal malformations at higher doses. In conclusion, our results show for the first time that developmental exposure to estrogens during certain stages can permanently influence bone tissue in an animal model. The observed changes appear to be due to an effect on bone cell programming since differences in bone cell number and activity are retained through adulthood.

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