Integrated RNA sequencing and biochemical studies reveal endoplasmic reticulum stress and autophagy dysregulation contribute to Tri (2-Ethylhexyl) phosphate (TEHP)-induced cell injury in Sertoli cells

Chen, Pengchen1,2,3; Song, Yali1; Tang, Li1; Qiu, Zhuolin4; Chen, Junhui2,3; Xia, Siyu1; Iyaswamy, Ashok5,6; Cai, Jing1; Sun, Yan1; Yang, Chuanbin2,3; Wang, Jigang1,2,3,7,8

2024-11-01

10.1016/j.envpol.2024.124536

ENVIRONMENTAL POLLUTION   影响因子和分区

0269-7491

1873-6424

Tri (2-Ethylhexyl) phosphate (TEHP), widely used as a fire retardant and plasticizer, has been commonly found in the environment. Its potential health-related risks, especially reproductive toxicity, have aroused concern. However, the potential cellular mechanisms remain unexplored. In this study, we aimed to investigate the molecular mechanisms underlying TEHP-caused cell damage in Sertoli cells, which play a crucial role in supporting spermatogenesis. Our findings indicate that TEHP induces apoptosis in 15P-1 mouse Sertoli cells. Subsequently, we conducted RNA sequencing analyses, which suggested that ER stress, autophagy, and MAPKrelated pathways may participate in TEHP-induced cytotoxicity. Furthermore, we demonstrated that TEHP triggers ER stress, activates p38 MAPK, and inhibits autophagy flux. Then, we showed that the inhibition of ER stress or p38 MAPK activation attenuates TEHP-induced apoptosis, while the inhibition of autophagy flux is responsible for TEHP-induced apoptosis. These results collectively reveal that TEHP induces ER stress, activates p38, and inhibits autophagy flux, ultimately leading to apoptosis in Sertoli cells. These shed light on the molecular mechanisms underlying TEHP-associated testicular toxicity.

Tri (2-ethylhexyl) phosphate Sertoli cell Endoplasmic reticulum stress Autophagy dysregulation Reproductive toxicity

SCI ; EI

英语

通讯

Establishment of Sino-Austria "Belt and Road" Joint Laboratory on Traditional Chinese Medicine for Severe Infectious Diseases and Joint Research[2020YFE0205100] ; Innovation Team and Talents Cultivation Program of National Administration of Traditional Chinese Medicine[ZYYCXTD-C-202002] ; CACMS Innovation Fund["CI2023E002","CI2021A05101","CI2021A05104"] ; Scientific and Technological Innovation Project of China Academy of Chinese Medical Sciences[CI2021B014] ; Shenzhen Science and Technology Program["JCYJ20210324115800001","JCYJ20220818102613029","JCYJ20210324114014039"] ; Shenzhen Medical Research Fund of Shenzhen Medical Academy of Research and Translation[B2302051] ; Distinguished Expert Project of Sichuan Province Tianfu Scholar[CW202002] ; Fundamental Research Funds for the Central public welfare research institutes[ZZ13-ZD-07] ; National Natural Science Foundation of China[82374063]

Environmental Sciences & Ecology

Environmental Sciences

WOS:001288699000001

ELSEVIER SCI LTD

ENVIRONMENT/ECOLOGY

Web of Science

1.Southern Med Univ, Dongguan Maternal & Child Hlth Care Hosp, Postdoctoral Innovat Practice Base, Dongguan 523125, Guangdong, Peoples R China
2.Southern Univ Sci & Technol, Jinan Univ, Shenzhen Peoples Hosp, Shenzhen Inst Resp Dis,Affiliated Hosp 1,Clin Med, Shenzhen 518020, Guangdong, Peoples R China
3.Southern Univ Sci & Technol, Jinan Univ, Shenzhen Peoples Hosp, Shenzhen Clin Res Ctr Geriatr,Affiliated Hosp 1,Cl, Shenzhen 518020, Guangdong, Peoples R China
4.Southern Med Univ, Nanfang Hosp, Ctr Reprod Med, Dept Obstet & Gynecol, Guangzhou, Peoples R China
5.Hong Kong Baptist Univ, Sch Chinese Med, Hong Kong, Peoples R China
6.Karpagam Acad Higher Educ, Dept Biochem, Coimbatore 641021, India
7.China Acad Chinese Med Sci, Artemisinin Res Ctr, State Key Lab Qual Ensurance & Sustainable Use Dao, Beijing 100700, Peoples R China
8.China Acad Chinese Med Sci, Inst Chinese Mat Med, Beijing 100700, Peoples R China

Chen, Pengchen,Song, Yali,Tang, Li,et al. Integrated RNA sequencing and biochemical studies reveal endoplasmic reticulum stress and autophagy dysregulation contribute to Tri (2-Ethylhexyl) phosphate (TEHP)-induced cell injury in Sertoli cells[J]. ENVIRONMENTAL POLLUTION,2024,360.

Chen, Pengchen.,Song, Yali.,Tang, Li.,Qiu, Zhuolin.,Chen, Junhui.,...&Wang, Jigang.(2024).Integrated RNA sequencing and biochemical studies reveal endoplasmic reticulum stress and autophagy dysregulation contribute to Tri (2-Ethylhexyl) phosphate (TEHP)-induced cell injury in Sertoli cells.ENVIRONMENTAL POLLUTION,360.

Chen, Pengchen,et al."Integrated RNA sequencing and biochemical studies reveal endoplasmic reticulum stress and autophagy dysregulation contribute to Tri (2-Ethylhexyl) phosphate (TEHP)-induced cell injury in Sertoli cells".ENVIRONMENTAL POLLUTION 360(2024).