Abstract :
[en] Rat sexual maturation is preceded by a reduction of the interpulse interval (IPI) of gonadotropinreleasing
hormone (GnRH) neurosecretion. This work aims at studying disruption of that neuroendocrine
event in females after early exposure to a very low dose of Bisphenol A (BPA), a
ubiquitous endocrine disrupting chemical.
Female rats were exposed to vehicle or BPA 25 ng/kg.day, 25 g/kg.day, or 5 mg/kg.day from
postnatal day (PND) 1 to 5 or 15. Exposure to 25 ng/kg.day of BPA for 5 or 15 days was followed
by a delay in developmental reduction of GnRH IPI studied ex vivo on PND 20. After 15 days of
exposure to that low dose of BPA, vaginal opening tended to be delayed. In contrast, exposure to
BPA 5 mg/kg.day for 15 days resulted in a premature reduction inGnRHIPI and a trend toward early
vaginal opening. RNAseq analysis on PND20 indicated that exposure to BPA resulted in opposing
dose effectsonthemRNAexpression of hypothalamic genes involved inGABAA neurotransmission.
The study of GnRH secretion in vitro in the presence of GABAA receptor agonist/antagonist confirmed
an increased or a reduced GABAergic tone after in vivo exposure to the very low or the high
dose of BPA, respectively.
Overall, we show for the first time that neonatal 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 neuroendocrine maturation related to puberty through
increased inhibitory GABAergic neurotransmission.
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