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Environmental-Like Exposure to Low Levels of Estrogen Affects Sexual Behavior and Physiology of Female Rats

Department of Physiology (D.D.S., F.F.), University of Siena, 53100 Siena, Italy; Department of Evolutionary Biology (F.D.-F.), University of Florence, 50125 Florence, Italy; and Department of Biology and Evolution (L.F.), University of Ferrara, 44100 Ferrara, Italy

Address all correspondence and requests for reprints to: Dr. Daniele Della Seta, Department of Physiology, University of Siena, 53100 Siena, Italy. E-mail: dellasetad{at}unisi.it.

Xenoestrogens are endocrine-disrupting chemicals that mimic the action of endogenous estrogen hormones. Effects of xenoestrogen on aquatic wildlife are well documented, whereas the experimental evidence for impairment of reproductive behavior and physiology in mammals after exposure to xenoestrogens has been debated. The strongest arguments against such studies have been that the route, time course, and intensity of exposure did not simulate environmental exposure and that the chemicals tested have additional nonestrogenic toxic effects, hindering generalization of actual xenoestrogenic effects. Here we show that environmental-like exposure to the pure estrogen 17-ethinylestradiol during development alters reproductive behavior and physiology in adult female Sprague-Dawley rats. We simulated environmental exposure by giving low doses (0.4 and 0.004 µg/kg·d) of 17-ethinylestradiol orally to pregnant females from conception to weaning of the pups, which continued to receive the treatment until puberty. We studied the sexual behavior, estrous cycle, and estradiol plasma levels of intact female rats when they reached 3 months of age. Exposure to the higher dose strongly affected female sexual behavior and physiology, with suppression of lordosis and the estrous cycle and enhanced aggression toward males. The lower dose disrupted appetitive components of sexual behavior that influence the rate of copulation. Estradiol plasma levels were not affected by the treatment. Our study revealed that exposure to low oral doses of a pure estrogen during development alters female sexual behavior and physiology. These results suggest potential risks of reproductive failure from xenoestrogen exposure in realistic ecological conditions.