The impact of neonatal exposure to 17alpha-ethynylestradiol on the development of kisspeptin neurons in female rats

• Neonatal exposure to EE effects Kiss1 mRNA expression before weaning.
• The AVPV is more susceptible to neonatal EE treatment than the ARC.
• At relatively low EE doses, Kiss1 expression might be temporarily decreased before weaning.

Neonatal exposure to 17alpha-ethynylestradiol (EE) at relatively low doses leads to delayed effects characterized by the early onset of age-related anovulation. Kisspeptin neurons in the anteroventral periventricular nucleus (AVPV), located at the anterior hypothalamus, are proposed to play key roles in appearance of these delayed effects after maturation. To understand the initial changes, we investigated Kiss1 mRNA expression in the anterior and posterior hypothalamus before weaning in female rats that received neonatal exposure to EE at various doses (0.002–2000 μg/kg). The level of Kiss1 mRNA in the anterior hypothalamus was decreased from 0.002 μg/kg which did not induce delayed effects. In the posterior hypothalamus, Kiss1 mRNA expression did not differ among the groups except 2000 μg/kg group. These results suggest that neonatal exposure to EE affects the development of kisspeptin neurons and kisspeptin neurons in the AVPV are highly susceptible to neonatal EE treatment.