TCM Department, Children's Hospital of Fudan University, Shanghai 201102, China.
Pediatric Department, Ruijin Hospital affiliated to Shanghai Jiao Tong University, Shanghai 200020, China.
Reprod Toxicol. 2022 Jun;110:141-149. doi: 10.1016/j.reprotox.2022.04.005. Epub 2022 Apr 14.
Bisphenol A (BPA) is ubiquitous in the environment and its adverse effects on precocious puberty have been reported. But its mechanism is not clear. In the present study, the potential effects of BPA on endocrine functions of hypothalamus, especially in the arcuate (ARC) nucleus and anteroventral periventricular (AVPe) nucleus, were studied from postnatal day 15 (PND15) to PND35 in female Sprague-Dawley (SD) rats. Neonatal rats were exposed to 0.5 mg·kg·day BPA or corn oil vehicle from PND1 to PND14 via intramuscular injection. From PND20 to PND 25, BPA caused enrichment of H3K4me2 and H3K4me3 at Kiss1 promoter, concurrent with elevated gene expressions of Kiss1 and GnRH1 in ARC and strikingly increased serum E2 levels in BPA group on PND25. Until PND30, BPA induced obviously overexpression of Kiss1 and GnRH1 in AVPe nucleus. Subsequently, the vagina opening and first ovulation had occurred earlier in rats with BPA exposure in respect to vehicle by PND35. In this study, it is suggested that the effects of BPA on precocious puberty may be due to its action to activate Kiss1 gene in ARC during the juvenile period (from PND20 to PND25) firstly, subsequently to evoke the AVPe neurons, resulting in precocious puberty in the end.
双酚 A（BPA）在环境中无处不在，其对性早熟的不良影响已有报道。但其机制尚不清楚。本研究从出生后第 15 天（PND15）到第 35 天（PND35），在雌性 Sprague-Dawley（SD）大鼠中研究了 BPA 对下丘脑内分泌功能的潜在影响，特别是在弓状核（ARC）和前腹侧脑室周围核（AVPe）。新生大鼠从 PND1 到 PND14 通过肌肉注射接受 0.5mg·kg·day BPA 或玉米油载体。从 PND20 到 PND25，BPA 导致 Kiss1 启动子处 H3K4me2 和 H3K4me3 的富集，同时伴随着 ARC 中 Kiss1 和 GnRH1 基因表达的升高，以及 BPA 组血清 E2 水平在 PND25 时明显升高。直到 PND30，BPA 诱导了 AVPe 核中 Kiss1 和 GnRH1 的明显过表达。随后，与载体组相比，BPA 暴露组的大鼠阴道开口和首次排卵更早发生在 PND35。在这项研究中，BPA 引起性早熟的作用可能是由于其在幼年期（从 PND20 到 PND25）首先激活 ARC 中的 Kiss1 基因，随后激活 AVPe 神经元，最终导致性早熟。
