Developmental exposure to low levels of ethinylestradiol affects social play in juvenile male rats
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Toxicol Res. https://doi.org/10.1007/s43188-019-00035-z
Toxicological Research
ORIGINAL ARTICLE
Developmental exposure to low levels of ethinylestradiol affects social play in juvenile male rats Marco Zaccaroni1 · Alessandro Massolo2 · Laura Beani1 · Daniele Della Seta3 · Francesca Farabollini3 · Giulietta Giannelli1 · Leonida Fusani4 · Francesco Dessì‑Fulgheri1 Received: 26 August 2019 / Revised: 21 October 2019 / Accepted: 27 November 2019 © Korean Society of Toxicology 2020
Abstract Juvenile social play contributes to the development of adult social and emotional skills in humans and non-human animals and is therefore a useful endpoint to study the effects of endocrine disrupters on behavior in animal models. Ethinylestradiol (EE2), a widely produced, powerful synthetic estrogen is widespread in the environment mainly because it is a component of the contraceptive pill. To understand whether clinical or environmental exposure to E E2 during critical perinatal periods can affect male social play, we exposed 72 male Sprague–Dawley rats to E E2 or vehicle either during gestation (from gestation day (GD) 5 through 20) or during lactation (from postnatal day (PND) 1 through 21). Two doses of EE2 were used to treat the dams: a lower dose in the range of possible environmental exposure (4 ng/kg/day) and a higher dose similar to that received during contraceptive treatment (400 ng/kg/day). Social play was observed between PND 40 and 45. A principal component analysis (PCA) of frequencies of behavioral items observed during play sessions allowed to allocate behaviors to the two main components that we named aggressive-like play and defensive-like play. Aggressive-like play was increased by gestational and decreased by lactational exposure. Defensive-like play was decreased by treatment. For both types of play the lower dose (4 ng/kg/day) was as effective as the higher one. Total social activity was increased by gestational and decreased by lactational exposure. These findings provide further evidence that exposure to low and to very low doses of E E2 during critical periods of development can affect essential aspects of social behavior, and that the timing of exposure is critical to understand its developmental action. Keywords Endocrine disrupters · Ethinylestradiol · Xenoestrogens · Social play · Play fighting · Anogenital distance · Developmental windows · Cross-fostering · Rat
Leonida Fusani and Francesco Dessì-Fulgheri shared senior authorship. * Marco Zaccaroni [email protected] 1
Department di Biology, University of Firenze, Florence, Italy
2
Ethology Unit, Department of Biology, University of Pisa, Pisa, Italy and Laboratoire Chrono-environnement, Université Bourgogne Franche-Comté, Besançon, France
3
Department of Medicine, Surgery and Neuroscience University of Siena, Siena, Italy
4
Department of Cognitive Biology, University of Vienna, and Konrad Lorenz Institute of Ethology, University of Veterinary Medicine, Vienna, Austria
Abbreviations AFP α-Fetoprotein AGD Anogenita
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