It is now established that mycoestrogen zearalenone (ZEN) disrupts reproductive physiology, but the specific mechanisms by which this occurs remain unknown, especially in brain. Growing evidence suggests that populations of estradiol (E2)-sensitive neurons in anteroventral periventricular (AVPV) and arcuate (ARC) nuclei, especially kisspeptin neurons, play a pivotal role in the timing of puberty onset, ovulation, and normal reproduction. The present study was conducted to find whether the ZEN can cause estrogen-like actions during the critical period of neonatal differentiation. In this study, we compared the effect of neonatal exposure to sesame oil, E2 benzoate (EB, 20 mg/kg body weight [bw]), and 3 various doses: 0.2, 1, and 2 mg/kg bw of ZEN (0.2, 1, and 2 ZEN) on the onset of puberty and estrus cyclicity as well as ovarian follicular profile, kisspeptin expression, and neuronal density in AVPV and ARC hypothalamic nuclei and E2 and luteinizing hormone (LH) levels on postnatal day 70. Control mice received no treatment. Vaginal opening was significantly advanced by EB and 2 ZEN. Disrupted estrus cycles and decreased follicular profiles were observed in EB, 1 ZEN, and 2 ZEN animals. In addition, EB, 1 ZEN, and 2 ZEN reduced the expression of kisspeptin and neuronal density of AVPV and ARC nuclei and caused a decrease in the LH and an increase in E2 plasma levels. Taken together, our observations provide physiological evidence that neonatal exposure to ZEN exerts estrogen-like actions in the estrogen-sensitive hypothalamic AVPV and ARC nuclei, controlling reproductive functions in adult female mice.

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