Biochemical mechanisms of tributyltin chloride-induced cell toxicity in Sertoli cells
Tributyltin chloride (TBTCL) is a widely used fungicide and heat stabilizer in compositions of PVC. TBTCL has been detected in human bodies and potentially causes harmful effects on humans’ thyroid, cardiovascular and other organs. As one of the first examples of endocrine disruptors, the toxicity e...
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| Published in | Ecotoxicology and environmental safety Vol. 255; p. 114725 |
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| Main Authors | , , , , , , , , , |
| Format | Journal Article |
| Language | English |
| Published |
Netherlands
Elsevier Inc
15.04.2023
Elsevier |
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| Abstract | Tributyltin chloride (TBTCL) is a widely used fungicide and heat stabilizer in compositions of PVC. TBTCL has been detected in human bodies and potentially causes harmful effects on humans’ thyroid, cardiovascular and other organs. As one of the first examples of endocrine disruptors, the toxicity effects of TBTCL on the male reproduction system have aroused concerns. However, the potential cellular mechanisms are not fully explored. In the current study, by using Sertoli cells, a critical regulator of spermatogenesis as a cell model, we showed that with 200 nM exposure for 24 h, TBTCL causes apoptosis and cell cycle arrest. RNA sequencing analyses suggested that TBTCL probably activates endoplasmic reticulum (ER) stress, and disrupts autophagy. Biochemical analysis showed that TBTCL indeed induces ER stress and the dysregulation of autophagy. Interestingly, activation of ER stress and inhibition of autophagy is responsible for TBTCL-induced apoptosis and cell cycle arrest. Our results thus uncovered a novel insight into the cellular mechanisms for TBTCL-induced toxicology in Sertoli cells.
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•Tributyltin chloride causes apoptosis and cell cycle arrest in mouse Sertoli cells.•Tributyltin chloride induces endoplasmic reticulum (ER) stress and autophagy flux blockade.•Tributyltin chloride induced apoptosis and cell cycle arrest via autophagy process.•Disordered autophagy process is responsible for tributyltin chloride-induced apoptosis and cell cycle arrest.•We provided a new understanding in the mechanisms of TBTCL-induced testis toxicity. |
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| AbstractList | Tributyltin chloride (TBTCL) is a widely used fungicide and heat stabilizer in compositions of PVC. TBTCL has been detected in human bodies and potentially causes harmful effects on humans' thyroid, cardiovascular and other organs. As one of the first examples of endocrine disruptors, the toxicity effects of TBTCL on the male reproduction system have aroused concerns. However, the potential cellular mechanisms are not fully explored. In the current study, by using Sertoli cells, a critical regulator of spermatogenesis as a cell model, we showed that with 200 nM exposure for 24 h, TBTCL causes apoptosis and cell cycle arrest. RNA sequencing analyses suggested that TBTCL probably activates endoplasmic reticulum (ER) stress, and disrupts autophagy. Biochemical analysis showed that TBTCL indeed induces ER stress and the dysregulation of autophagy. Interestingly, activation of ER stress and inhibition of autophagy is responsible for TBTCL-induced apoptosis and cell cycle arrest. Our results thus uncovered a novel insight into the cellular mechanisms for TBTCL-induced toxicology in Sertoli cells.Tributyltin chloride (TBTCL) is a widely used fungicide and heat stabilizer in compositions of PVC. TBTCL has been detected in human bodies and potentially causes harmful effects on humans' thyroid, cardiovascular and other organs. As one of the first examples of endocrine disruptors, the toxicity effects of TBTCL on the male reproduction system have aroused concerns. However, the potential cellular mechanisms are not fully explored. In the current study, by using Sertoli cells, a critical regulator of spermatogenesis as a cell model, we showed that with 200 nM exposure for 24 h, TBTCL causes apoptosis and cell cycle arrest. RNA sequencing analyses suggested that TBTCL probably activates endoplasmic reticulum (ER) stress, and disrupts autophagy. Biochemical analysis showed that TBTCL indeed induces ER stress and the dysregulation of autophagy. Interestingly, activation of ER stress and inhibition of autophagy is responsible for TBTCL-induced apoptosis and cell cycle arrest. Our results thus uncovered a novel insight into the cellular mechanisms for TBTCL-induced toxicology in Sertoli cells. Tributyltin chloride (TBTCL) is a widely used fungicide and heat stabilizer in compositions of PVC. TBTCL has been detected in human bodies and potentially causes harmful effects on humans’ thyroid, cardiovascular and other organs. As one of the first examples of endocrine disruptors, the toxicity effects of TBTCL on the male reproduction system have aroused concerns. However, the potential cellular mechanisms are not fully explored. In the current study, by using Sertoli cells, a critical regulator of spermatogenesis as a cell model, we showed that with 200 nM exposure for 24 h, TBTCL causes apoptosis and cell cycle arrest. RNA sequencing analyses suggested that TBTCL probably activates endoplasmic reticulum (ER) stress, and disrupts autophagy. Biochemical analysis showed that TBTCL indeed induces ER stress and the dysregulation of autophagy. Interestingly, activation of ER stress and inhibition of autophagy is responsible for TBTCL-induced apoptosis and cell cycle arrest. Our results thus uncovered a novel insight into the cellular mechanisms for TBTCL-induced toxicology in Sertoli cells. [Display omitted] •Tributyltin chloride causes apoptosis and cell cycle arrest in mouse Sertoli cells.•Tributyltin chloride induces endoplasmic reticulum (ER) stress and autophagy flux blockade.•Tributyltin chloride induced apoptosis and cell cycle arrest via autophagy process.•Disordered autophagy process is responsible for tributyltin chloride-induced apoptosis and cell cycle arrest.•We provided a new understanding in the mechanisms of TBTCL-induced testis toxicity. Tributyltin chloride (TBTCL) is a widely used fungicide and heat stabilizer in compositions of PVC. TBTCL has been detected in human bodies and potentially causes harmful effects on humans' thyroid, cardiovascular and other organs. As one of the first examples of endocrine disruptors, the toxicity effects of TBTCL on the male reproduction system have aroused concerns. However, the potential cellular mechanisms are not fully explored. In the current study, by using Sertoli cells, a critical regulator of spermatogenesis as a cell model, we showed that with 200 nM exposure for 24 h, TBTCL causes apoptosis and cell cycle arrest. RNA sequencing analyses suggested that TBTCL probably activates endoplasmic reticulum (ER) stress, and disrupts autophagy. Biochemical analysis showed that TBTCL indeed induces ER stress and the dysregulation of autophagy. Interestingly, activation of ER stress and inhibition of autophagy is responsible for TBTCL-induced apoptosis and cell cycle arrest. Our results thus uncovered a novel insight into the cellular mechanisms for TBTCL-induced toxicology in Sertoli cells. |
| ArticleNumber | 114725 |
| Author | Li, Huiying Tang, Li Chen, Junhui Zhang, Wei Cheng, Guangqing Zhong, Wenbin Fan, Tianyun Wang, Jigang Chen, Pengchen Song, Yali |
| Author_xml | – sequence: 1 givenname: Pengchen surname: Chen fullname: Chen, Pengchen organization: Dongguan Maternal and Child Health Care Hospital, Postdoctoral Innovation Practice Base of Southern Medical University, Dongguan 523125, Guangdong, China – sequence: 2 givenname: Junhui surname: Chen fullname: Chen, Junhui organization: Department of Nephrology, Shenzhen key Laboratory of Kidney Diseases, and Shenzhen Clinical Research Centre for Geriatrics, Shenzhen People's Hospital (The Second Clinical Medical College, Jinan University, The First Affiliated Hospital, Southern University of Science and Technology), Shenzhen 518020, China – sequence: 3 givenname: Wei surname: Zhang fullname: Zhang, Wei organization: Department of Nephrology, Shenzhen key Laboratory of Kidney Diseases, and Shenzhen Clinical Research Centre for Geriatrics, Shenzhen People's Hospital (The Second Clinical Medical College, Jinan University, The First Affiliated Hospital, Southern University of Science and Technology), Shenzhen 518020, China – sequence: 4 givenname: Li surname: Tang fullname: Tang, Li organization: Dongguan Maternal and Child Health Care Hospital, Postdoctoral Innovation Practice Base of Southern Medical University, Dongguan 523125, Guangdong, China – sequence: 5 givenname: Guangqing surname: Cheng fullname: Cheng, Guangqing organization: Artemisinin Research Center, and Institute of Chinese Materia Medica, China Academy of Chinese Medical Sciences, Beijing 100700, China – sequence: 6 givenname: Huiying surname: Li fullname: Li, Huiying organization: Dongguan Maternal and Child Health Care Hospital, Postdoctoral Innovation Practice Base of Southern Medical University, Dongguan 523125, Guangdong, China – sequence: 7 givenname: Tianyun surname: Fan fullname: Fan, Tianyun organization: Dongguan Maternal and Child Health Care Hospital, Postdoctoral Innovation Practice Base of Southern Medical University, Dongguan 523125, Guangdong, China – sequence: 8 givenname: Jigang surname: Wang fullname: Wang, Jigang email: jgwang@icmm.ac.cn organization: Dongguan Maternal and Child Health Care Hospital, Postdoctoral Innovation Practice Base of Southern Medical University, Dongguan 523125, Guangdong, China – sequence: 9 givenname: Wenbin surname: Zhong fullname: Zhong, Wenbin email: 929313440@qq.com organization: Dongguan Maternal and Child Health Care Hospital, Postdoctoral Innovation Practice Base of Southern Medical University, Dongguan 523125, Guangdong, China – sequence: 10 givenname: Yali surname: Song fullname: Song, Yali email: syl@smu.edu.cn organization: Dongguan Maternal and Child Health Care Hospital, Postdoctoral Innovation Practice Base of Southern Medical University, Dongguan 523125, Guangdong, China |
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| Keywords | Sertoli cell Tributyltin chloride Autophagy Endoplasmic reticulum stress |
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| SubjectTerms | Apoptosis Autophagy Endoplasmic Reticulum Stress Humans Male Sertoli cell Sertoli Cells Spermatogenesis Thyroid Gland Trialkyltin Compounds - toxicity Tributyltin chloride |
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| Title | Biochemical mechanisms of tributyltin chloride-induced cell toxicity in Sertoli cells |
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