Liu Miao Qing, Chen Hai Qiong, Dai Hai Peng, Li Jing Jing, Tian Fu Hong, Wang Yi Yan, Chen Cong De, Li Xiao Heng, Li Jun Wei, Li Zhong Rong, Ge Ren Shan
Department of Pediatric Surgery, the Second Affiliated Hospital and Yuying Children's Hospital of Wenzhou Medical University, Wenzhou 325027, Zhejiang, China;Key Laboratory of Structural Malformations in Children of Zhejiang Province, Wenzhou 325000, Zhejiang, China.
Key Laboratory of Structural Malformations in Children of Zhejiang Province, Wenzhou 325000, Zhejiang, China.
Biomed Environ Sci. 2023 Jan 20;36(1):60-75. doi: 10.3967/bes2023.006.
This study investigated the effects of bis (2-butoxyethyl) phthalate (BBOP) on the onset of male puberty by affecting Leydig cell development in rats.
Thirty 35-day-old male Sprague-Dawley rats were randomly allocated to five groups mg/kg bw per day that were gavaged for 21 days with BBOP at 0, 10, 100, 250, or 500 mg/kg bw per day. The hormone profiles; Leydig cell morphological metrics; mRNA and protein levels; oxidative stress; and AKT, mTOR, ERK1/2, and GSK3β pathways were assessed.
BBOP at 250 and/or 500 mg/kg bw per day decreased serum testosterone, luteinizing hormone, and follicle-stimulating hormone levels mg/kg bw per day ( < 0.05). BBOP at 500 mg/kg bw per day decreased Leydig cell number mg/kg bw per day and downregulated , , , and in the testes, and and mRNAs in the pituitary gland ( < 0.05). The malondialdehyde content in the testis significantly increased, while and mRNAs were markedly down-regulated, by BBOP treatment at 250-500 mg/kg bw per day ( < 0.05). Furthermore, BBOP at 500 mg/kg bw per day decreased AKT1/AKT2, mTOR, and ERK1/2 phosphorylation, and GSK3β and SIRT1 levels mg/kg bw per day ( < 0.05). Finally, BBOP at 100 or 500 μmol/L induced ROS and apoptosis in Leydig cells after 24 h of treatment ( < 0.05).
BBOP delays puberty onset by increasing oxidative stress and apoptosis in Leydig cells in rats.
The graphical abstract is available on the website www.besjournal.com.
本研究通过影响大鼠睾丸间质细胞发育，探讨邻苯二甲酸二（2-丁氧基乙基）酯（BBOP）对雄性青春期启动的影响。
将30只35日龄雄性Sprague-Dawley大鼠随机分为五组，分别以每天0、10、100、250或500mg/kg体重的剂量经口灌胃给予BBOP，持续21天。评估激素水平、睾丸间质细胞形态学指标、mRNA和蛋白质水平、氧化应激以及AKT、mTOR、ERK1/2和GSK3β信号通路。
每天250和/或500mg/kg体重的BBOP降低了血清睾酮、黄体生成素和促卵泡激素水平（P<0.05）。每天500mg/kg体重的BBOP减少了睾丸间质细胞数量，并下调了睾丸中的StAR、CYP11A1、3β-HSD和17β-HSD以及垂体中的LHβ和FSHβ mRNA水平（P<0.05）。每天250 - 500mg/kg体重的BBOP处理显著增加了睾丸中的丙二醛含量，同时显著下调了Nrf2和HO-1 mRNA水平（P<0.05）。此外，每天500mg/kg体重的BBOP降低了AKT1/AKT2、mTOR和ERK1/2的磷酸化水平以及GSK3β和SIRT1水平（P<0.05）。最后，100或500μmol/L的BBOP处理24小时后诱导了睾丸间质细胞中的活性氧生成和细胞凋亡（P<0.05）。
BBOP通过增加大鼠睾丸间质细胞中的氧化应激和细胞凋亡来延迟青春期启动。
图形摘要可在网站www.besjournal.com上获取。
