Bis (2-butoxyethyl) Phthalate Delays Puberty Onset by Increasing Oxidative Stress and Apoptosis in Leydig Cells in Rats.

Miao Qing Liu; Hai Qiong Chen; Hai Peng Dai; Jing Jing LI; Fu Hong Tian; Yi Yan Wang; Cong De Chen; Xiao Heng LI; Jun Wei LI; Zhong Rong LI; Ren Shan GE

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Bis (2-butoxyethyl) Phthalate Delays Puberty Onset by Increasing Oxidative Stress and Apoptosis in Leydig Cells in Rats.

Author: Miao Qing LIU ^{1
,

2} ; Hai Qiong CHEN ^{1
,

2} ; Hai Peng DAI ^{1
,

2} ; Jing Jing LI ² ; Fu Hong TIAN ² ; Yi Yan WANG ² ; Cong De CHEN ^{1
,

2} ; Xiao Heng LI ² ; Jun Wei LI ² ; Zhong Rong LI ^{1
,

2} ; Ren Shan GE ^{1
,

2}
Author Information

1. Department of Pediatric Surgery, the Second Affiliated Hospital and Yuying Children's Hospital of Wenzhou Medical University, Wenzhou 325027, Zhejiang, China
2. Key Laboratory of Structural Malformations in Children of Zhejiang Province, Wenzhou 325000, Zhejiang, China.
Publication Type:Journal Article
Keywords: Bis (2-butoxyethyl) phthalate; Gonadotropin; Leydig cells; Oxidative stress; Testosterone
MeSH: Rats; Male; Animals; Leydig Cells/metabolism*; Testosterone; Glycogen Synthase Kinase 3 beta/pharmacology*; Rats, Sprague-Dawley; Sexual Maturation; Testis; Oxidative Stress; TOR Serine-Threonine Kinases/metabolism*; Apoptosis
From: Biomedical and Environmental Sciences 2023;36(1):60-75
CountryChina
Language:English
Abstract: OBJECTIVE:This study investigated the effects of bis (2-butoxyethyl) phthalate (BBOP) on the onset of male puberty by affecting Leydig cell development in rats.
METHODS: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.
RESULTS: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 (P < 0.05). BBOP at 500 mg/kg bw per day decreased Leydig cell number mg/kg bw per day and downregulated Cyp11a1, Insl3, Hsd11b1, and Dhh in the testes, and Lhb and Fshb mRNAs in the pituitary gland (P < 0.05). The malondialdehyde content in the testis significantly increased, while Sod1 and Sod2 mRNAs were markedly down-regulated, by BBOP treatment at 250-500 mg/kg bw per day (P < 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 (P < 0.05). Finally, BBOP at 100 or 500 μmol/L induced ROS and apoptosis in Leydig cells after 24 h of treatment in vitro (P < 0.05).
CONCLUSION:BBOP delays puberty onset by increasing oxidative stress and apoptosis in Leydig cells in rats.
UNLABELLED:The graphical abstract is available on the website www.besjournal.com.