During the past decades, advancement in onset of pubertal timing has been observed. Recent changes also include a trend towards delay in completion of puberty, raising the question of environmental influences. Since pubertal timing appears to be programmed during foetal and neonatal life, factors such as endocrine disrupting chemicals (EDCs) could possibly interfere at those early stages. As an example, the insecticide DDT could partly account for the increased prevalence of sexual precocity among children adopted from developing countries. Bisphenol A (BPA) is a ubiquitous EDC present in plastics and cans. Human data suggested no association between BPA exposure and pubertal timing or even delayed menarche whereas studies in rodents indicated possible early onset of puberty.
EFSA has currently set the level of safe daily BPA exposure to 4 μg/kg per day. Female rats were exposed to vehicle or BPA 25 ng/kg per day or 5 mg/kg per day from postnatal day 1 to 5 or 15. After 15 days of exposure to 25 ng/kg per day of BPA, vaginal opening (VO) was delayed following a delayed developmental acceleration of pulsatile gonadotropin-releasing hormone (GnRH) secretion. Inversely, exposure to BPA 5 mg/kg per day for 15 days resulted in early VO following a premature acceleration of GnRH secretion. On PND 20, the mRNA expression of hypothalamic genes involved in GABAA neurotransmission showed opposing changes depending on the dose of BPA. The study of GnRH secretion after BPA exposure in presence of GABAA receptor agonist/antagonist confirmed that a very low BPA dose leads to delayed puberty through an increased GABAergic tone whereas a high BPA dose leads to early puberty through reduced GABAergic tone. Thus, early postnatal exposure to BPA leads to opposing dose-dependent effects on the neuroendocrine control of puberty in the female rat. A very low and environmentally relevant dose of BPA delays maturation of the neuroendocrine control of puberty through alteration of GABAergic neurotransmission.