Prepubertal overexposure to manganese induce precocious puberty through GABA receptor/nitric oxide pathway in immature female rats.

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ID: 74328
2020
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Abstract
Gamma-aminobutyric acid (GABA) plays a critical role in regulation of gonadotropin-releasing hormone (GnRH) through GABA receptor (GABAR). Nitric oxide (NO) production has correlation with GABA and regulates GnRH secretion. This study was performed to examine the mechanisms by which manganese (Mn) accelerate puberty onset involves GABAR/NO pathway in the preoptic area-anterior hypothalamus (POA-AH) in immature female rats. First, female rats received daily dose of MnCl 0 (saline), 2.5, 5 and 10 mg/kg b.w by oral gavage during postnatal day (PND) 21-32. Animals administered with 10 mg/kg MnCl exhibited earlier puberty onset age and advanced ovary and uterus development than these in saline-treatment group. Furthermore, we found that decrease of GABAR result in elevated production of nitric oxide synthase1 (NOS1), NO and GnRH in the POA-AH. Second, we recorded the neuronal spikes alternation after perfusion with GABAR inhibitor bicuculline (BIC), GABAR agonist isoguvacine (isog), and MnCl from the POA-AH in acute brain slices of PND21 rats. Spontaneous firing revealed a powerful GABAR-mediated action on immature POA-AH and confirm that MnCl has a significant effect on GABAR. Third, we revealed that decrease in NOS1 and NO production by treatment with isog-alone or isog+MnCl contribute to the decrease of GnRH in the POA-AH and a delayed puberty onset age compared to treatment with MnCl-alone. Together, these results suggested that excessive exposure to MnCl stimulates NO production through decreased GABAR in the POA-AH to advance puberty onset in immature female rats.
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yang2020prepubertalecotoxicology Use this key to autocite in the manuscript while using SciMatic Manuscript Manager or Thesis Manager
Authors Yang, Xinxin;Tan, Jichun;Xu, Xiaoyan;Yang, Haibo;Wu, Fengdi;Xu, Bin;Liu, Wei;Shi, Pengcheng;Xu, Zhaofa;Deng, Yu;
Journal Ecotoxicology and environmental safety
Year 2020
DOI
S0147-6513(19)31229-1
URL
Keywords
nitric oxide manganese gaba(a)r gnrh precocious puberty

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