Cadmium induces testosterone synthesis disorder by testicular cell damage via TLR4/MAPK/NF-κB signaling pathway leading to reduced sexual behavior in piglets

Cadmium (Cd) is a highly toxic metal pollutant that can endanger the life and health of animals. Toll-like receptor 4 (TLR4) can result in testicular cell damage by positively regulating mitogen-activated protein kinase (MAPK)/nuclear factor-kappaB (NF-κB) signaling pathway. Meanwhile, Testosterone...

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Main Authors: Yulong Li, Yue Zhang, Rui Feng, Peng Zheng, He Huang, Sitong Zhou, Wenbo Ji, Fushuo Huang, Honggui Liu, Guixue Zhang
Format: Article
Language:English
Published: Elsevier 2022-03-01
Series:Ecotoxicology and Environmental Safety
Subjects:
Online Access:http://www.sciencedirect.com/science/article/pii/S0147651322001853
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author Yulong Li
Yue Zhang
Rui Feng
Peng Zheng
He Huang
Sitong Zhou
Wenbo Ji
Fushuo Huang
Honggui Liu
Guixue Zhang
author_facet Yulong Li
Yue Zhang
Rui Feng
Peng Zheng
He Huang
Sitong Zhou
Wenbo Ji
Fushuo Huang
Honggui Liu
Guixue Zhang
author_sort Yulong Li
collection DOAJ
description Cadmium (Cd) is a highly toxic metal pollutant that can endanger the life and health of animals. Toll-like receptor 4 (TLR4) can result in testicular cell damage by positively regulating mitogen-activated protein kinase (MAPK)/nuclear factor-kappaB (NF-κB) signaling pathway. Meanwhile, Testosterone (T) synthesis disorder can affect sexual behavior. However, the harmful influence of Cd on animal sexual behavior during its growth and development and the role of TLR4/MAPK/NF-κB signaling pathway in testicular cell damage and testosterone production remained poorly understood. Forty-two-day-old male piglets were fed with diets that contained CdCl2 (20 mg Cd/kg) for 40 days to explore the toxic effects of Cd on sexual behavior. The results showed that Cd activated TLR4, promoted MAPK (p-ERK, p-JNK, and p-p38)/NF-κB expression, induced apoptosis (Caspase-3, Cleaved Caspase3, Bax, Cyt-c, and Caspase-9 expression increased, but Bcl-2 expression decreased) and necroptosis (MLKL, RIPK1, and RIPK3 expression increased) in piglet testis. In addition, Cd exposure decreased mRNA expression of STAR, CYP11A1, 3β-HSD, CYP17A1, and 17β-HSD of testis and the concentrations of T and thyroid-stimulating hormone (TSH). Both the mRNA and protein expression levels of the major genes in TLR4/MAPK/NF-κB signaling pathway, apoptosis signaling pathway, and necroptosis signaling pathway increased significantly and the expression levels of testosterone decreased gradually in pig Leydig cells cultured in vitro after being treated with different concentrations of Cd. Moreover, Cd reduced sexual behavior (the parameters of sniffing, chin resting, and mounting decreased) in piglets. In conclusion, Cd induced testicular cell damage via TLR4/MAPK/NF-κB signaling pathway leading to testosterone synthesis disorder and sexual behavior reduction in piglets.
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spelling doaj.art-ddda35b4fe45442bbd02f70d333f0b972022-12-21T18:35:32ZengElsevierEcotoxicology and Environmental Safety0147-65132022-03-01233113345Cadmium induces testosterone synthesis disorder by testicular cell damage via TLR4/MAPK/NF-κB signaling pathway leading to reduced sexual behavior in pigletsYulong Li0Yue Zhang1Rui Feng2Peng Zheng3He Huang4Sitong Zhou5Wenbo Ji6Fushuo Huang7Honggui Liu8Guixue Zhang9College of Animal Science and Technology, Northeast Agricultural University, Harbin 150030, PR ChinaCollege of Veterinary Medicine, Northeast Agricultural University, Harbin 150030, PR ChinaCollege of Animal Science and Technology, Northeast Agricultural University, Harbin 150030, PR ChinaCollege of Animal Science and Technology, Northeast Agricultural University, Harbin 150030, PR ChinaCollege of Animal Science and Technology, Northeast Agricultural University, Harbin 150030, PR ChinaCollege of Animal Science and Technology, Northeast Agricultural University, Harbin 150030, PR ChinaCollege of Animal Science and Technology, Northeast Agricultural University, Harbin 150030, PR ChinaCollege of Animal Science and Technology, Northeast Agricultural University, Harbin 150030, PR ChinaCollege of Animal Science and Technology, Northeast Agricultural University, Harbin 150030, PR China; Key Laboratory of Swine Facilities Engineering, Ministry of Agriculture and Rural Affairs, Harbin 150030, PR China; Corresponding author at: College of Animal Science and Technology, Northeast Agricultural University, Harbin 150030, PR China.College of Animal Science and Technology, Northeast Agricultural University, Harbin 150030, PR China; Corresponding author.Cadmium (Cd) is a highly toxic metal pollutant that can endanger the life and health of animals. Toll-like receptor 4 (TLR4) can result in testicular cell damage by positively regulating mitogen-activated protein kinase (MAPK)/nuclear factor-kappaB (NF-κB) signaling pathway. Meanwhile, Testosterone (T) synthesis disorder can affect sexual behavior. However, the harmful influence of Cd on animal sexual behavior during its growth and development and the role of TLR4/MAPK/NF-κB signaling pathway in testicular cell damage and testosterone production remained poorly understood. Forty-two-day-old male piglets were fed with diets that contained CdCl2 (20 mg Cd/kg) for 40 days to explore the toxic effects of Cd on sexual behavior. The results showed that Cd activated TLR4, promoted MAPK (p-ERK, p-JNK, and p-p38)/NF-κB expression, induced apoptosis (Caspase-3, Cleaved Caspase3, Bax, Cyt-c, and Caspase-9 expression increased, but Bcl-2 expression decreased) and necroptosis (MLKL, RIPK1, and RIPK3 expression increased) in piglet testis. In addition, Cd exposure decreased mRNA expression of STAR, CYP11A1, 3β-HSD, CYP17A1, and 17β-HSD of testis and the concentrations of T and thyroid-stimulating hormone (TSH). Both the mRNA and protein expression levels of the major genes in TLR4/MAPK/NF-κB signaling pathway, apoptosis signaling pathway, and necroptosis signaling pathway increased significantly and the expression levels of testosterone decreased gradually in pig Leydig cells cultured in vitro after being treated with different concentrations of Cd. Moreover, Cd reduced sexual behavior (the parameters of sniffing, chin resting, and mounting decreased) in piglets. In conclusion, Cd induced testicular cell damage via TLR4/MAPK/NF-κB signaling pathway leading to testosterone synthesis disorder and sexual behavior reduction in piglets.http://www.sciencedirect.com/science/article/pii/S0147651322001853CadmiumTLR4/MAPK/NF-κB signaling pathwayTesticular cell damageTestosteroneSexual behavior
spellingShingle Yulong Li
Yue Zhang
Rui Feng
Peng Zheng
He Huang
Sitong Zhou
Wenbo Ji
Fushuo Huang
Honggui Liu
Guixue Zhang
Cadmium induces testosterone synthesis disorder by testicular cell damage via TLR4/MAPK/NF-κB signaling pathway leading to reduced sexual behavior in piglets
Ecotoxicology and Environmental Safety
Cadmium
TLR4/MAPK/NF-κB signaling pathway
Testicular cell damage
Testosterone
Sexual behavior
title Cadmium induces testosterone synthesis disorder by testicular cell damage via TLR4/MAPK/NF-κB signaling pathway leading to reduced sexual behavior in piglets
title_full Cadmium induces testosterone synthesis disorder by testicular cell damage via TLR4/MAPK/NF-κB signaling pathway leading to reduced sexual behavior in piglets
title_fullStr Cadmium induces testosterone synthesis disorder by testicular cell damage via TLR4/MAPK/NF-κB signaling pathway leading to reduced sexual behavior in piglets
title_full_unstemmed Cadmium induces testosterone synthesis disorder by testicular cell damage via TLR4/MAPK/NF-κB signaling pathway leading to reduced sexual behavior in piglets
title_short Cadmium induces testosterone synthesis disorder by testicular cell damage via TLR4/MAPK/NF-κB signaling pathway leading to reduced sexual behavior in piglets
title_sort cadmium induces testosterone synthesis disorder by testicular cell damage via tlr4 mapk nf κb signaling pathway leading to reduced sexual behavior in piglets
topic Cadmium
TLR4/MAPK/NF-κB signaling pathway
Testicular cell damage
Testosterone
Sexual behavior
url http://www.sciencedirect.com/science/article/pii/S0147651322001853
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