Exposure to DEHP induces testis toxicity and injury through the ROS/mTOR/NLRP3 signaling pathway in immature rats

As the most abundantly used phthalate derivative, di-(2-ethylhexyl) phthalate (DEHP) leads to reproductive disorders, especially in males. Testicular injury can be triggered when the testis is exposed to DEHP during the immature stage. However, the potential mechanism is largely unclear. In the pres...

Descripción completa

Guardado en:

Detalles Bibliográficos
Autores principales:	Yifan Hong, Yu Zhou, Lianju Shen, Yuexin Wei, Chunlan Long, Yan Fu, Huan Wu, Junke Wang, Yuhao Wu, Shengde Wu, Guanghui Wei
Formato:	article
Lenguaje:	EN
Publicado:	Elsevier 2021
Materias:	DEHP ROS Pyroptosis Testicular injury Environmental pollution TD172-193.5 Environmental sciences GE1-350
Acceso en línea:	https://doaj.org/article/2df0e65399624ee8b6c9710c6f60b616
Etiquetas:	Agregar Etiqueta Sin Etiquetas, Sea el primero en etiquetar este registro!

id	oai:doaj.org-article:2df0e65399624ee8b6c9710c6f60b616
record_format	dspace
spelling	oai:doaj.org-article:2df0e65399624ee8b6c9710c6f60b6162021-11-06T04:15:00ZExposure to DEHP induces testis toxicity and injury through the ROS/mTOR/NLRP3 signaling pathway in immature rats0147-651310.1016/j.ecoenv.2021.112889https://doaj.org/article/2df0e65399624ee8b6c9710c6f60b6162021-12-01T00:00:00Zhttp://www.sciencedirect.com/science/article/pii/S0147651321010010https://doaj.org/toc/0147-6513As the most abundantly used phthalate derivative, di-(2-ethylhexyl) phthalate (DEHP) leads to reproductive disorders, especially in males. Testicular injury can be triggered when the testis is exposed to DEHP during the immature stage. However, the potential mechanism is largely unclear. In the present study, Sprague-Dawley rats were exposed to 0, 250 and 500 mg/kg/day DEHP from postnatal day (PND) 20 to PND 30. The spermatogonia cell line GC-1 and spermatocyte cell line GC-2 were exposed to different doses of monoethylhexyl phthalate (MEHP), a metabolite of DEHP. Testicular injury was observed. Oxidative stress was evaluated both in vivo and in vitro. Our results showed that after DEHP exposure, the testicular structure was damaged and spermatogenesis was disturbed. We also found that oxidative stress was increased, as indicated by the upregulation of the important factors in the antioxidant pathway. Furthermore, the expression of autophagy-related proteins was significantly downregulated. Autophagy inhibition led to activation of the pyroptosis pathway. Nucleotide-binding and oligomerisation (NOD) domain-like receptor (NLR) family pyrin domain (PYD)-containing 3 (NLRP3), Caspase-1 and cytokine interleukin-1β (IL-1β) were significantly upregulated. Additionally, an imbalance in self-renewal and differentiation was observed in germ cells after DEHP exposure, causing the cessation of germ cell development. In summary, these data suggest that DEHP exposure enhances oxidative stress, downregulates autophagy, induces NLRP3 inflammasome activation and subsequently triggers pyroptosis in vivo and in vitro, which provides novel insight into DEHP-related injury in immature testes in the context of pyroptosis.Yifan HongYu ZhouLianju ShenYuexin WeiChunlan LongYan FuHuan WuJunke WangYuhao WuShengde WuGuanghui WeiElsevierarticleDEHPROSPyroptosisTesticular injuryEnvironmental pollutionTD172-193.5Environmental sciencesGE1-350ENEcotoxicology and Environmental Safety, Vol 227, Iss , Pp 112889- (2021)
institution	DOAJ
collection	DOAJ
language	EN
topic	DEHP ROS Pyroptosis Testicular injury Environmental pollution TD172-193.5 Environmental sciences GE1-350
spellingShingle	DEHP ROS Pyroptosis Testicular injury Environmental pollution TD172-193.5 Environmental sciences GE1-350 Yifan Hong Yu Zhou Lianju Shen Yuexin Wei Chunlan Long Yan Fu Huan Wu Junke Wang Yuhao Wu Shengde Wu Guanghui Wei Exposure to DEHP induces testis toxicity and injury through the ROS/mTOR/NLRP3 signaling pathway in immature rats
description	As the most abundantly used phthalate derivative, di-(2-ethylhexyl) phthalate (DEHP) leads to reproductive disorders, especially in males. Testicular injury can be triggered when the testis is exposed to DEHP during the immature stage. However, the potential mechanism is largely unclear. In the present study, Sprague-Dawley rats were exposed to 0, 250 and 500 mg/kg/day DEHP from postnatal day (PND) 20 to PND 30. The spermatogonia cell line GC-1 and spermatocyte cell line GC-2 were exposed to different doses of monoethylhexyl phthalate (MEHP), a metabolite of DEHP. Testicular injury was observed. Oxidative stress was evaluated both in vivo and in vitro. Our results showed that after DEHP exposure, the testicular structure was damaged and spermatogenesis was disturbed. We also found that oxidative stress was increased, as indicated by the upregulation of the important factors in the antioxidant pathway. Furthermore, the expression of autophagy-related proteins was significantly downregulated. Autophagy inhibition led to activation of the pyroptosis pathway. Nucleotide-binding and oligomerisation (NOD) domain-like receptor (NLR) family pyrin domain (PYD)-containing 3 (NLRP3), Caspase-1 and cytokine interleukin-1β (IL-1β) were significantly upregulated. Additionally, an imbalance in self-renewal and differentiation was observed in germ cells after DEHP exposure, causing the cessation of germ cell development. In summary, these data suggest that DEHP exposure enhances oxidative stress, downregulates autophagy, induces NLRP3 inflammasome activation and subsequently triggers pyroptosis in vivo and in vitro, which provides novel insight into DEHP-related injury in immature testes in the context of pyroptosis.
format	article
author	Yifan Hong Yu Zhou Lianju Shen Yuexin Wei Chunlan Long Yan Fu Huan Wu Junke Wang Yuhao Wu Shengde Wu Guanghui Wei
author_facet	Yifan Hong Yu Zhou Lianju Shen Yuexin Wei Chunlan Long Yan Fu Huan Wu Junke Wang Yuhao Wu Shengde Wu Guanghui Wei
author_sort	Yifan Hong
title	Exposure to DEHP induces testis toxicity and injury through the ROS/mTOR/NLRP3 signaling pathway in immature rats
title_short	Exposure to DEHP induces testis toxicity and injury through the ROS/mTOR/NLRP3 signaling pathway in immature rats
title_full	Exposure to DEHP induces testis toxicity and injury through the ROS/mTOR/NLRP3 signaling pathway in immature rats
title_fullStr	Exposure to DEHP induces testis toxicity and injury through the ROS/mTOR/NLRP3 signaling pathway in immature rats
title_full_unstemmed	Exposure to DEHP induces testis toxicity and injury through the ROS/mTOR/NLRP3 signaling pathway in immature rats
title_sort	exposure to dehp induces testis toxicity and injury through the ros/mtor/nlrp3 signaling pathway in immature rats
publisher	Elsevier
publishDate	2021
url	https://doaj.org/article/2df0e65399624ee8b6c9710c6f60b616
work_keys_str_mv	AT yifanhong exposuretodehpinducestestistoxicityandinjurythroughtherosmtornlrp3signalingpathwayinimmaturerats AT yuzhou exposuretodehpinducestestistoxicityandinjurythroughtherosmtornlrp3signalingpathwayinimmaturerats AT lianjushen exposuretodehpinducestestistoxicityandinjurythroughtherosmtornlrp3signalingpathwayinimmaturerats AT yuexinwei exposuretodehpinducestestistoxicityandinjurythroughtherosmtornlrp3signalingpathwayinimmaturerats AT chunlanlong exposuretodehpinducestestistoxicityandinjurythroughtherosmtornlrp3signalingpathwayinimmaturerats AT yanfu exposuretodehpinducestestistoxicityandinjurythroughtherosmtornlrp3signalingpathwayinimmaturerats AT huanwu exposuretodehpinducestestistoxicityandinjurythroughtherosmtornlrp3signalingpathwayinimmaturerats AT junkewang exposuretodehpinducestestistoxicityandinjurythroughtherosmtornlrp3signalingpathwayinimmaturerats AT yuhaowu exposuretodehpinducestestistoxicityandinjurythroughtherosmtornlrp3signalingpathwayinimmaturerats AT shengdewu exposuretodehpinducestestistoxicityandinjurythroughtherosmtornlrp3signalingpathwayinimmaturerats AT guanghuiwei exposuretodehpinducestestistoxicityandinjurythroughtherosmtornlrp3signalingpathwayinimmaturerats
_version_	1718443906899640320

Exposure to DEHP induces testis toxicity and injury through the ROS/mTOR/NLRP3 signaling pathway in immature rats

Ejemplares similares