Exposure to 2,3,7,8-tetrachlorodibenzo-p-dioxin promotes inflammation in mouse testes: The critical role of Klotho in Sertoli cells

Meihua Jin, Jing Lou, Huihui Yu, Miao Miao, Guangchuan Wang, Hao Ai, Yu Huang, Sangwon Han, Donghe Han, Guang Yu

Research output: Contribution to journalArticle

Abstract

Increasing evidence shows that 2,3,7,8-tetrachlorodibenzo-p-dioxin(TCDD) enhances inflammation, and inflammation has a significant negative impact on fertility. Therefore, the aim of this study was to investigate the effects of TCDD on testis inflammation. Pregnant mice and primary Sertoli cells were treated with TCDD, and male offspring and Sertoli cells were treated with lipopolysaccharides(LPS). We then measured testis apoptotic cells, proinflammatory cytokines, and observed the Klotho/PDLIM2/p65 pathway. In vivo results revealed that TCDD further enhanced LPS-increased testis apoptotic cells and concentrations of testicular proinflammatory cytokines (IL1β, IL18, and IL12) (p < 0.05). An in vitro investigation showed the levels of proinflammatory cytokines were increased in TCDD + LPS-treated cells compared with LPS-treated cells (p < 0.05). Compared with the LPS-treated cells, expression of Klotho and PDLIM2 was significantly decreased in TCDD + LPS-treated cells (p < 0.05), while expression of p65 and NLRP3 were significantly increased in the cotreatment cells (p < 0.05). However, the addition of Klotho to the TCDD + LPS-cotreated cells significantly increased PDLIM2 and decreased p65 activation and NLRP3 (p < 0.05). Meanwhile, mRNA levels and the secretion of proinflammatory cytokines were both suppressed by exogenous Klotho (p < 0.05). Administration of Klotho decreased TCDD + LPS-induced cytokines and apoptosis in mice (p < 0.05). Taken together, TCDD may increase testicular inflammation by affecting the secretion of proinflammatory cytokines in Sertoli cells via the Klotho/PDLIM2/p65 pathway, which influences the testicular microenvironment and induces germ cell apoptosis.

Original languageEnglish
Pages (from-to)134-143
Number of pages10
JournalToxicology Letters
Volume295
DOIs
Publication statusPublished - 2018 Oct 1

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Sertoli Cells
Testis
Lipopolysaccharides
Inflammation
Cells
Cytokines
Apoptosis
Polychlorinated Dibenzodioxins
1,4-dioxin
Interleukin-18
Interleukin-12
Germ Cells
Fertility
Chemical activation
Messenger RNA

All Science Journal Classification (ASJC) codes

  • Toxicology

Cite this

Jin, Meihua ; Lou, Jing ; Yu, Huihui ; Miao, Miao ; Wang, Guangchuan ; Ai, Hao ; Huang, Yu ; Han, Sangwon ; Han, Donghe ; Yu, Guang. / Exposure to 2,3,7,8-tetrachlorodibenzo-p-dioxin promotes inflammation in mouse testes : The critical role of Klotho in Sertoli cells. In: Toxicology Letters. 2018 ; Vol. 295. pp. 134-143.
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abstract = "Increasing evidence shows that 2,3,7,8-tetrachlorodibenzo-p-dioxin(TCDD) enhances inflammation, and inflammation has a significant negative impact on fertility. Therefore, the aim of this study was to investigate the effects of TCDD on testis inflammation. Pregnant mice and primary Sertoli cells were treated with TCDD, and male offspring and Sertoli cells were treated with lipopolysaccharides(LPS). We then measured testis apoptotic cells, proinflammatory cytokines, and observed the Klotho/PDLIM2/p65 pathway. In vivo results revealed that TCDD further enhanced LPS-increased testis apoptotic cells and concentrations of testicular proinflammatory cytokines (IL1β, IL18, and IL12) (p < 0.05). An in vitro investigation showed the levels of proinflammatory cytokines were increased in TCDD + LPS-treated cells compared with LPS-treated cells (p < 0.05). Compared with the LPS-treated cells, expression of Klotho and PDLIM2 was significantly decreased in TCDD + LPS-treated cells (p < 0.05), while expression of p65 and NLRP3 were significantly increased in the cotreatment cells (p < 0.05). However, the addition of Klotho to the TCDD + LPS-cotreated cells significantly increased PDLIM2 and decreased p65 activation and NLRP3 (p < 0.05). Meanwhile, mRNA levels and the secretion of proinflammatory cytokines were both suppressed by exogenous Klotho (p < 0.05). Administration of Klotho decreased TCDD + LPS-induced cytokines and apoptosis in mice (p < 0.05). Taken together, TCDD may increase testicular inflammation by affecting the secretion of proinflammatory cytokines in Sertoli cells via the Klotho/PDLIM2/p65 pathway, which influences the testicular microenvironment and induces germ cell apoptosis.",
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Exposure to 2,3,7,8-tetrachlorodibenzo-p-dioxin promotes inflammation in mouse testes : The critical role of Klotho in Sertoli cells. / Jin, Meihua; Lou, Jing; Yu, Huihui; Miao, Miao; Wang, Guangchuan; Ai, Hao; Huang, Yu; Han, Sangwon; Han, Donghe; Yu, Guang.

In: Toxicology Letters, Vol. 295, 01.10.2018, p. 134-143.

Research output: Contribution to journalArticle

TY - JOUR

T1 - Exposure to 2,3,7,8-tetrachlorodibenzo-p-dioxin promotes inflammation in mouse testes

T2 - The critical role of Klotho in Sertoli cells

AU - Jin, Meihua

AU - Lou, Jing

AU - Yu, Huihui

AU - Miao, Miao

AU - Wang, Guangchuan

AU - Ai, Hao

AU - Huang, Yu

AU - Han, Sangwon

AU - Han, Donghe

AU - Yu, Guang

PY - 2018/10/1

Y1 - 2018/10/1

N2 - Increasing evidence shows that 2,3,7,8-tetrachlorodibenzo-p-dioxin(TCDD) enhances inflammation, and inflammation has a significant negative impact on fertility. Therefore, the aim of this study was to investigate the effects of TCDD on testis inflammation. Pregnant mice and primary Sertoli cells were treated with TCDD, and male offspring and Sertoli cells were treated with lipopolysaccharides(LPS). We then measured testis apoptotic cells, proinflammatory cytokines, and observed the Klotho/PDLIM2/p65 pathway. In vivo results revealed that TCDD further enhanced LPS-increased testis apoptotic cells and concentrations of testicular proinflammatory cytokines (IL1β, IL18, and IL12) (p < 0.05). An in vitro investigation showed the levels of proinflammatory cytokines were increased in TCDD + LPS-treated cells compared with LPS-treated cells (p < 0.05). Compared with the LPS-treated cells, expression of Klotho and PDLIM2 was significantly decreased in TCDD + LPS-treated cells (p < 0.05), while expression of p65 and NLRP3 were significantly increased in the cotreatment cells (p < 0.05). However, the addition of Klotho to the TCDD + LPS-cotreated cells significantly increased PDLIM2 and decreased p65 activation and NLRP3 (p < 0.05). Meanwhile, mRNA levels and the secretion of proinflammatory cytokines were both suppressed by exogenous Klotho (p < 0.05). Administration of Klotho decreased TCDD + LPS-induced cytokines and apoptosis in mice (p < 0.05). Taken together, TCDD may increase testicular inflammation by affecting the secretion of proinflammatory cytokines in Sertoli cells via the Klotho/PDLIM2/p65 pathway, which influences the testicular microenvironment and induces germ cell apoptosis.

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