Abstract：Objective To evaluate the effects of neonatal exposure to different doses of bisphenol A (BPA) on the vaginal opening day (VOD), hypothalamic Kiss-1 mRNA expression, and ovarian estrogen receptor (ER) mRNA expression in female rats. Methods Neonatal female Sprague-Dawley (SD) rats were randomly divided into six groups: blank control, vehicle, 17β-estradiol (17β-estradiol, E2, 10 μg/d), low-dose BPA [25 μg(kg·d)], medium-dose BPA [50 μg(kg·d)], and high-dose BPA groups [250 μg(kg·d)]. The rats were subcutaneously injected with respective agents on postnatal days 0-6. The VOD was recorded, and each rat was sacrificed on the same day. The hypothalamus and ovary were taken and weighed, and the organ coefficients of hypothalamus and ovary were calculated. The hypothalamic Kiss-1 mRNA expression and ovarian ERα and ERβ mRNA expression were measured by real-time PCR. Results Compared with the control group, the E2 and medium-and high-dose BPA groups had advanced VOD, and the E2 group had significantly reduced hypothalamic Kiss-1 mRNA expression and ovarian ERβ mRNA expression (PConclusions Neonatal exposure to medium-and high-dose BPA[50 and 250 μg/(kg·d)] can induce precocious puberty in rats, but it may not result from the change in hypothalamic Kiss-1 mRNA expression. Neonatal exposure to low-dose BPA [25 μg/(kg·d)] does not induce precocious puberty in rats.
YANG Fan,CHEN Lin-Qi,JIN Mei-Fang et al. Impact of neonatal exposure to different doses of bisphenol A on puberty in female rats[J]. CJCP, 2014, 16(7): 754-758.
Krishnan AV, Stathis P, Permuth SF, et al. Bisphenol-A: an estrogenic substance is released from polycarbonate flasks during autoclaving[J]. Endocrinology, 1993, 132(6): 2279-2286.
[2]
Adewale HB, Jefferson WN, Newbold RR, et al. Neonatal bisphenol-a exposure alters rat reproductive development and ovarian morphology without impairing activation of gonadotropin-releasing hormone neurons[J]. Biol Reprod, 2009, 81(4): 690-699.
[3]
Bouskine A, Nebout M, Brucker-Davis F, et al. Low doses of bisphenol A promote human seminoma cell proliferation by activating PKA and PKG via a membrane G-protein-coupled estrogen receptor[J]. Environ Health Perspect, 2009, 117(7): 1053-1058.
[4]
Tyl RW, Myers CB, Marr MC, et al. Three-generation reproductive toxicity study of dietary bisphenol A in CD Sprague-Dawley rats[J]. Toxicol Sci, 2002, 68(1): 121-146.
[5]
Roa J, Vigo E, Castellano JM, et al. Follicle-stimulating hormone responses to kisspeptin in the female rat at the preovulatory period: modulation by estrogen and progesterone receptors[J]. Endocrinology, 2008, 149(11): 5783-5790.
[6]
Losa-Ward SM, Todd KL, McCaffrey KA, et al. Disrupted organization of RFamide pathways in the hypothalamus is associated with advanced puberty in female rats neonatally exposed to bisphenol A[J]. Biol Reprod, 2012, 87(2): 28.
[7]
Navarro VM, Castellano JM, Fernandez-Fernandez R, et al. Characterization of the potent luteinizing hormone-releasing activity of Kiss-1 peptide, the natural ligand of GPR54[J]. Endocrinology, 2005, 146(1): 156-163.
[8]
Lapatto R, Pallais JC, Zhang D, et al. Kiss1-/-mice exhibit more variable hypogonadism than Gpr54-/-mice[J]. Endocrinology, 2007, 148(10): 4927-4936.
[9]
Bottner M, Thelen P, Jarry H. Estrogen receptor beta: tissue distribution and the still largely enigmatic physiological function[J]. J Steroid Biochem Mol Biol, 2014, 139: 245-251.
Navarro VM, Sanchez-Garrido MA, Castellano JM, et al. Persistent impairment of hypothalamic Kiss-1 system after exposures to estrogenic compounds at critical periods of brain sex differentiation[J]. Endocrinology, 2009, 150(5): 2359-2367.
Organization WH. Joint FAO/WHO Expert Meeting to Review Toxicological and Health Aspects of Bisphenol A: Summary Report[J]. World Health Organization, Ottawa, CA. 2010.
Patisaul HB, Todd KL, Mickens JA, et al. Impact of neonatal exposure to the ERalpha agonist PPT, bisphenol-A or phytoestrogens on hypothalamic kisspeptin fiber density in male and female rats[J]. Neurotoxicology, 2009, 30(3): 350-357.
