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Effect of methoxychlor on the onset of puberty in immature female rats : Early activation of hypothalamus-pituitary-gonadal axis
Background & Objectives: Methoxychlor(MET), an organochlorine insecticide, has been thought a potent endocrine disrupting chemical. The present study was undertaken to examine whether short-term exposure to MET can alter the onset of puberty and the associated reproductive parameters such as hormone receptor expressions in prepubertal female rats. Method: MET (1, 10 and 100 mg/kg/day) was administered daily from postnatal day 25 (PND 25) through the PND 34, and the animals were sacrificed on the PND 35. The first V.O. day was monitored, and the weights of reproductive tissues were measured. To assess the structural alterations in the ovary and uterus, the tissues were embedded in paraffin and stained for histological analysis. The transcriptional activities of hypothalamic and pituitary genes were measured using quantitative RT-PCRs. The uterine and hypothalamic proteins were extracted and used for the ER western blotting. Results: As a result, 100 mg group showed advanced V.O. than control, 1 mg group and 10 mg group. The wet weights of ovaries from MET-treated animal dose-dependently increased. The uterine weights were increased in 1 mg group and 10 mg group, while the 100 mg group samples were not significantly different from control tissues. The adrenal, kidney, spleen and thymus weights were not shown any significant change. Corpora lutea and fully grown follicles were observed in the ovaries from the 100 mg group, while numerous primary and secondary follicles were observed in the ovaries from control group. Myometrial thickness of MET-treated group was dose-dependently increased. Epithelial hypertrophy and well-developed glands were observed in the uterus from the 10 mg groups. Conclusions: The present study demonstrated that the short-term exposure to MET during the critical period of prepubertal stage could activate a reproductive endocrine system, resulting the early onset of puberty in immature female rats. Our study suggests that MET’s disrupting effect might be derived from premature activation of key reproduction-related genes in hypothalamus-pituitary neuroendocrine circuit.
