Developmental Exposure to Low Levels of Ethinylestradiol Affects Play Behavior in Juvenile Female Rats

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) is a widely produced, powerful synthetic estrogen that is widespread in the environment mainly because is a component of the contraceptive pill. In addition, fetuses may be exposed to EE2 when pregnancy is undetected during contraceptive treatment. To understand whether exposure to EE₂ during gestation or lactation affects social play, we exposed 72 female Sprague-Dawley rats to EE₂ or vehicle either during gestation (gestation day (GD) 5 through GD 20) or during lactation (from postnatal day (PND) 1 through PND 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 equivalent to that received during contraceptive treatment (400 ng/kg/day). Behavioral testing was carried out between PND 40 and 45. A principal component analysis of frequencies of behavioral items observed during play sessions identified three main components: defensive-like play, aggressive-like play, and exploration. Aggressive-like play was significantly increased by both doses of EE₂, and the gestational administration was in general more effective than the lactational one. Defensive-like play and exploration were not significantly affected by treatment. This research showed that low and very low doses of EE₂ that mimic clinical or environmental exposure during development can affect important aspects of social behavior even during restricted time windows.