Effect of early postnatal exposure to 17α-ethinylestradiol on female rat reproductive physiology

Objective 17α-Ethinylestradiol (EE2) is a synthetic compound used as an oral contraceptive in birth control pills. EE2 is a major contaminant in aquatic environments. It is considered an endocrine-disrupting chemical due to its oestrogenic activity. This study investigates the effect of repeated exposure to EE2 at a dose of 1 µg/kg·(body weight)/day on reproductive function and metabolism. Methods Female Sprague–Dawley rats were subcutaneously injected with EE2 at a dose of 1 µg/kg·(body weight)/day from postnatal day 1 until postnatal day 5, which corresponds to a highly sensitive period of neuroendocrine system organisation. Results The anogenital distance, body weight and blood levels of insulin and glucose of EE2-treated female rats were not different from those of control rats. These results indicate that growth and glucose metabolism were unaffected by treatment. In contrast, vaginal opening occurred significantly earlier in EE2-treated females than in control females. In adulthood, these females present an alteration of their oestrous cyclicity, characterised by persistent vaginal oestrus. Moreover, treated females showed altered uterine and ovarian morphology associated with lower circulating levels of oestradiol and progesterone. Conclusion These results indicate precocious onset of puberty and dysfunction of the reproductive organs. Therefore, early postnatal exposure to EE2 at a dose of 1 µg/kg·bw/d has delayed adverse effects on reproductive function.