17α-methyltestosterone induced hepatocyte apoptosis through endoplasmic reticulum stress in <italic style="font-style: italic">Takifugu fasciatus</italic>

Xuanyin CHEN; Sheng LUO; Yanfang LI; Rui LI; Xiaojun LI; Zhengyang HU; Shaowu YIN; Tao WANG

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17α-methyltestosterone induced hepatocyte apoptosis through endoplasmic reticulum stress in Takifugu fasciatus

Biology | Updated：2025-02-19

- 17α-methyltestosterone induced hepatocyte apoptosis through endoplasmic reticulum stress in Takifugu fasciatus
- 17α-methyltestosterone induced hepatocyte apoptosis through endoplasmic reticulum stress in Takifugu fasciatus
- 海洋湖沼学报(英文) 2025年43卷第1期页码：219-231
- Affiliations：
  
  1.College of Marine Science and Engineering, Jiangsu Province Engineering Research Center for Aquatic Animals Breeding and Green Efficient Aquacultural Technology, Nanjing Normal University, Nanjing 210023, China
  2.Co-Innovation Center for Marine Bio-Industry Technology of Jiangsu Province, Lianyungang 222005, China
- Author bio：
  
  seawater88@126.com
- Funds：
  
  the Jiangsu Agriculture Science and Technology Innovation Fund (No. CX (22) 2029), the National Natural Science Foundation of China(32172948;31800436);the “JBGS” Project of Seed Industry Revitalization in Jiangsu Province (No. JBGS (2021)034), and the Postgraduate Research & Practice Innovation Program of Jiangsu Province(SJCX23_0616)
- DOI：
  中图分类号：
- 收稿：2024-01-16，
  
  纸质出版：2025-01-01
- Accepted：
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17α-methyltestosterone induced hepatocyte apoptosis through endoplasmic reticulum stress in Takifugu fasciatus[J]. 海洋湖沼学报(英文), 2025,43(1):219-231.

CHEN Xuanyin,LUO Sheng,LI Yanfang,et al.17α-methyltestosterone induced hepatocyte apoptosis through endoplasmic reticulum stress in Takifugu fasciatus[J].Journal of Oceanology and Limnology,2025,43(01):219-231.
17α-methyltestosterone induced hepatocyte apoptosis through endoplasmic reticulum stress in Takifugu fasciatus[J]. 海洋湖沼学报(英文), 2025,43(1):219-231. DOI：

CHEN Xuanyin,LUO Sheng,LI Yanfang,et al.17α-methyltestosterone induced hepatocyte apoptosis through endoplasmic reticulum stress in Takifugu fasciatus[J].Journal of Oceanology and Limnology,2025,43(01):219-231. DOI：

摘要

Abstract

17α-methyltestosterone (17α-MT) is an emerging pollutant

which is harmful to the endocrine system and reproduction of fish. We investigated the effects of different concentrations of 17α-MT (0

and 100 mg/kg) on endoplasmic reticulum stress (ERS) and apoptosis in the liver of

Takifugu

fasciatus

. Results show that: (1) with the increase of 17α-MT treatment concentration

liver transaminases (alanine aminotransferase; aspartate aminotransferase) and the mRNA expression of ERS marker genes (glucose-regulated protein 78; calreticulin) of

fasciatus

were significantly increased compared with the control group (

0.05); (2) the activity of succinate dehydrogenase (SDH)

Caspase3 and Caspase9 in the liver of

fasciatus

increased with the increase of 17α-MT concentration compared with the control group (

0.05); (3) by using 4-phenylbutyricacid (4-PBA) inhibitors to stimulate ERS through in vitro experiments

the expression of ERS

and apoptosis-related genes significantly decreased (

0.05)

and the apoptosis rate of

fasciatus

hepatocytes was significantly inhibited (

0.05) under 17α-MT treatment. This study confirmed that ERS played an important role in the induction of apoptosis in the hepatocytes of

fasciatus

which enriched the ecotoxicological information of environmental androgens.

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Keywords

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Abo-Al-Ela H G , El-Nahas A F , Mahmoud S et al . 2017 . The extent to which immunity, apoptosis and detoxification gene expression interact with 17 alpha-methyltestosterone . Fish & Shellfish Immunology , 60 : 289 - 298 , https://doi.‍o‍rg/10.1016/j.fsi.2016.11.057 https://doi.‍o‍rg/10.1016/j.fsi.2016.11.057 . https://do 10.1016/j.fsi.2016.11.057 http://dx.doi.org/10.1016/j.fsi.2016.11.057

Aspuria P J P , Lunt S Y , Väremo L et al . 2014 . Succinate dehydrogenase inhibition leads to epithelial-mesenchymal transition and reprogrammed carbon metabolism . Cancer & Metabolism , 2 : 21 , https://doi.org/10.1186/2049-3002-2-21 https://doi.org/10.1186/2049-3002-2-21 .

Battogtokh G , Choi Y S , Kang D S et al . 2018 . Mitochondria-targeting drug conjugates for cytotoxic, anti-oxidizing and sensing purposes: current strategies and future perspectives . Acta Pharmaceutica Sinica B , 8 ( 6 ): 862 - 880 , https://doi.org/10.1016/j.apsb.2018.05.006 https://doi.org/10.1016/j.apsb.2018.05.006 .

Carnevali O , Santangeli S , Forner-Piquer I et al . 2018 . Endocrine-disrupting chemicals in aquatic environment: what are the risks for fish gametes? Fish Physiology and Biochemistry , 44 ( 6 ): 1561 - 1576 , https://doi.‍org/10.1007/s10695-018-0507-z https://doi.‍org/10.1007/s10695-018-0507-z . https://do 10.1007/s10695-018-0507-z http://dx.doi.org/10.1007/s10695-018-0507-z

Cejudo-Marín R , Tárrega C , Nunes-Xavier C E et al . 2012 . Caspase-3 cleavage of DUSP6/MKP3 at the interdomain region generates active MKP3 fragments that regulate ERK 1 /2 subcellular localization and function . Journal of Molecular Biology , 420 ( 1-2 ): 128 - 138 , https://doi.org/10.1016/j.jmb.2012.04.004 https://doi.org/10.1016/j.jmb.2012.04.004 .

Deng J , Yu L Q , Liu C S et al . 2009 . Hexabromocyclododecane-induced developmental toxicity and apoptosis in zebrafish embryos . Aquatic Toxicology , 93 ( 1 ): 29 - 366 , https://doi.org/10.1016/j.aquatox.2009.03.001 https://doi.org/10.1016/j.aquatox.2009.03.001 .

Ding J N , Zhang S S , Razanajatovo R M et al . 2018 . Accumulation, tissue distribution, and biochemical effects of polystyrene microplastics in the freshwater fish red tilapia ( Oreochromis niloticus ) . Environmental Pollution , 238 : 1 - 9 , https://doi.org/10.1016/j.envpol.2018.03.001 https://doi.org/10.1016/j.envpol.2018.03.001 .

Fu D Y , Hu Y D , Chu P et al . 2021 . Histopathological and calreticulin changes in the liver and gill of Takifugu fasciatus demonstrate the effects of copper nanoparticle and copper sulphate exposure . Aquaculture Reports , 20 : 100662 , https://doi.org/10.1016/j.aqrep.2021.100662 https://doi.org/10.1016/j.aqrep.2021.100662 .

Gelles J D , Mohammed J N , Chen Y Y et al . 2022 . A kinetic fluorescence polarization ligand assay for monitoring BAX early activation . Cell Reports Methods , 2 ( 3 ): 100174 , https://doi.org/10.1016/j.crmeth.2022.100174 https://doi.org/10.1016/j.crmeth.2022.100174 .

Gore A C , Chappell V A , Fenton S E et al . 2015 . Executive summary to EDC-2: the endocrine society’s second scientific statement on endocrine-disrupting chemicals . Endocrine Reviews , 36 ( 6 ): 593 - 602 , https://doi.org/10.1210/er.2015-1093 https://doi.org/10.1210/er.2015-1093 .

Hetz C . 2012 . The unfolded protein response: controlling cell fate decisions under ER stress and beyond . Nature Reviews Molecular Cell Biology , 13 ( 2 ): 89 - 102 , https://doi.org/10.1038/nrm3270 https://doi.org/10.1038/nrm3270 .

Hourihan J M , Mazzeo L E M , Fernández-Cárdenas L P et al . 2016 . Cysteine sulfenylation directs IRE-1 to activate the SKN-1/Nrf2 antioxidant response . Molecular Cell , 63 ( 4 ): 553 - 566 , https://doi.org/10.1016/j.molcel.2016.07.019 https://doi.org/10.1016/j.molcel.2016.07.019 .

Huang B , Wang B , Ren D et al . 2013 . Occurrence, removal and bioaccumulation of steroid estrogens in Dianchi Lake catchment, China . Environment International , 59 : 262 - 273 , https://doi.org/10.1016/j.envint.2013.06.018 https://doi.org/10.1016/j.envint.2013.06.018 .

Ji W , Liang H L , Zhou W S et al . 2013 . Apoptotic responses of zebrafish ( Danio rerio ) after exposure with microcystin-LR under different ambient temperatures . Journal of Applied Toxicology , 33 ( 8 ): 799 - 806 , https://doi.org/10.1002/jat.2735 https://doi.org/10.1002/jat.2735 .

Kasonga T K , Coetzee M A A , Kamika I et al . 2021 . Endocrine-disruptive chemicals as contaminants of emerging concern in wastewater and surface water: a review . Journal of Environmental Management , 277 : 111485 , https://doi.org/10.1016/j.jenvman.2020.111485 https://doi.org/10.1016/j.jenvman.2020.111485 .

Kim J H , Kang J C . 2016 . Oxidative stress, neurotoxicity, and metallothionein (MT) gene expression in juvenile rock fish Sebastes schlegelii under the different levels of dietary chromium (Cr 6+ ) exposure . Ecotoxicology and Environmental Safety , 125 : 78 - 84 , https://doi.org/10.1016/j.ecoenv.2015.12.001 https://doi.org/10.1016/j.ecoenv.2015.12.001 .

Lin J Y , Ho T J , Tsai B C K et al . 2021 . Exercise renovates H 2 S and Nrf2-related antioxidant pathways to suppress apoptosis in the natural ageing process of male rat cortex . Biogerontology , 22 ( 5 ): 495 - 506 , https://doi.‍org/10.1007/s10522-021-09929-8 https://doi.‍org/10.1007/s10522-021-09929-8 . https://do 10.1007/s10522-021-09929-8 http://dx.doi.org/10.1007/s10522-021-09929-8

Lin T T , Liu X , Xiao D X et al . 2017 . Plasma levels of immune factors and sex steroids in the male seahorse Hippocampus erectus during a breeding cycle . Fish Physiology and Biochemistry , 43 ( 3 ): 889 - 899 , https://doi.org/10.1007/s10695-017-0343-6 https://doi.org/10.1007/s10695-017-0343-6 .

Liu H J , Dong M , Jiang W D et al . 2022 . Acute nitrite exposure-induced oxidative damage, endoplasmic reticulum stress, autophagy and apoptosis caused gill tissue damage of grass carp ( Ctenopharyngodon idella ): relieved by dietary protein . Ecotoxicology and Environmental Safety , 243 : 113994 , https://doi.org/10.1016/j.ecoenv.2022.113994 https://doi.org/10.1016/j.ecoenv.2022.113994 .

Liu S , Xu P , Liu X G et al . 2020 . Histological and sex-determining genes expression effects of 17α-methyltestosterone on mandarin fish Siniperca chuatsi gonad development . Research Square , https://doi.org/10.21203/rs.2.20021/v1 https://doi.org/10.21203/rs.2.20021/v1 .

Liu S Z , Chen Y , Li T Y et al . 2023 . Effects of 17α-methyltestosterone on the transcriptome and sex hormones in the brain of Gobiocypris rarus . International Journal of Molecular Sciences , 24 ( 4 ): 3571 , https://doi.org/10.3390/IJMS2403571 https://doi.org/10.3390/IJMS2403571 .

Lopez-Cruzan M , Sharma R , Tiwari M et al . 2016 . Caspase-2 resides in the mitochondria and mediates apoptosis directly from the mitochondrial compartment . Cell Death Discovery , 2 : 16005 , https://doi.org/10.1038/cddiscovery.2016.5 https://doi.org/10.1038/cddiscovery.2016.5 .

Luo T , Chen B H , Wang X B . 2015 . 4-PBA prevents pressure overload-induced myocardial hypertrophy and interstitial fibrosis by attenuating endoplasmic reticulum stress . Chemico-Biological Interactions , 242 : 99 - 106 , https://doi.org/10.1016/j.cbi.2015.09.025 https://doi.org/10.1016/j.cbi.2015.09.025 .

Lyu Q , Hu J , Yang X K et al . 2019 . Expression profiles of dmrts and foxls during gonadal development and sex reversal induced by 17α-methyltestosterone in the orange-spotted grouper . General and Comparative Endocrinology , 274 : 26 - 36 , https://doi.org/10.1016/j.ygcen.2018.12.014 https://doi.org/10.1016/j.ygcen.2018.12.014 .

Ma S S , Liu Y X , Zhao C et al . 2023 . Copper induced intestinal inflammation response through oxidative stress induced endoplasmic reticulum stress in Takifugu fasciatus . Aquatic Toxicology , 261 : 106634 , https://doi.org/10.1016/J.AQUATOX.2023.106634 https://doi.org/10.1016/J.AQUATOX.2023.106634 .

Mandriani B , Castellana S , Rinaldi C et al . 2016 . Identification of P53-target genes in Danio rerio . Scientific Reports , 6 : 32474 , https://doi.org/10.1038/srep32474 https://doi.org/10.1038/srep32474 .

Mandula J K , Chang S , Mohamed E et al . 2022 . Ablation of the endoplasmic reticulum stress kinase PERK induces paraptosis and type I interferon to promote anti-tumor T cell responses . Cancer Cell , 40 ( 10 ): 1145 - 1160.e9 , https://doi.org/10.1016/J.CCELL.2022.08.016 https://doi.org/10.1016/J.CCELL.2022.08.016 .

Ni X Q , Lu W W , Zhang J S et al . 2018 . Inhibition of endoplasmic reticulum stress by intermedin1-53 attenuates angiotensin II-induced abdominal aortic aneurysm in ApoE KO Mice . Endocrine , 62 ( 1 ): 90 - 106 , https://doi.org/10.1007/s12020-018-1657-6 https://doi.org/10.1007/s12020-018-1657-6 .

Owen R , Jobling S . 2012 . Environmental science: the hidden costs of flexible fertility . Nature , 485 ( 7399 ): 441 , https://doi.org/10.1038/485441a https://doi.org/10.1038/485441a .

Pihán P , Carreras-Sureda A , Hetz C . 2017 . BCL-2 family: integrating stress responses at the ER to control cell demise . Cell Death & Differentiation , 24 ( 9 ): 1478 - 1487 , https://doi.org/10.1038/cdd.2017.82 https://doi.org/10.1038/cdd.2017.82 .

Prakash S , Kumar A , Okla M K et al . 2022 . Physiological responses of the symbiotic shrimp Ancylocaris brevicarpalis and its host sea anemone Stichodactyla haddoni to ocean acidification . Marine Pollution Bulletin , 175 : 113287 , https://doi.‍org/10.1016/j.marpolbul.2021.113287 https://doi.‍org/10.1016/j.marpolbul.2021.113287 . https://do 10.1016/j.marpolbul.2021.113287 http://dx.doi.org/10.1016/j.marpolbul.2021.113287

Ramesh M , Anitha S , Poopal R K et al . 2018 . Evaluation of acute and sublethal effects of chloroquine (C18H26CIN 3 ) on certain enzymological and histopathological biomarker responses of a freshwater fish Cyprinus carpio . Toxicology Reports , 5 : 18 - 27 , https://doi.org/10.1016/j.toxrep.2017.11.006 https://doi.org/10.1016/j.toxrep.2017.11.006 .

Ramsdale M . 2012 . Programmed cell death in the cellular differentiation of microbial eukaryotes . Current Opinion in Microbiology , 15 ( 6 ): 646 - 652 , https://doi.org/10.1016/j.mib.2012.09.005 https://doi.org/10.1016/j.mib.2012.09.005 .

Rupa E J , Nahar J , Al-Amin M et al . 2023 . Cissus antractica -ZnO NPs induce apoptosis in A549 cells through ROS-generated p53/Bcl-2/Bax signaling pathways and inhibition of inflammatory cytokines . Coatings , 13 ( 12 ): 2077 , https://doi.org/10.3390/coatings13122077 https://doi.org/10.3390/coatings13122077 .

Seo M Y , Rhee K . 2018 . Caspase-mediated cleavage of the centrosomal proteins during apoptosis . Cell Death & Disease , 9 ( 5 ): 571 , https://doi.org/10.1038/s41419-018-0632-8 https://doi.org/10.1038/s41419-018-0632-8 .

Song Y F , Luo Z , Huang C et al . 2015 . Endoplasmic reticulum stress-related genes in yellow catfish Pelteobagrus fulvidraco : molecular characterization, tissue expression, and expression responses to dietary copper deficiency and excess. G3 (Genes Genomes Genetics) , 5 ( 10 ): 2091 - 2104 , https://doi.org/10.1534/g3.115.019950 https://doi.org/10.1534/g3.115.019950 .

Tan Y , Lin B , Ye Y et al . 2015 . Differential expression of serum microRNAs in cirrhosis that evolve into hepatocellular carcinoma related to hepatitis B virus . Oncology Reports , 33 ( 6 ): 2863 - 2870 , https://doi.org/10.3892/or.2015.3924 https://doi.org/10.3892/or.2015.3924 .

Tao N P , Wu R , Zhou P G et al . 2014 . Characterization of odor-active compounds in cooked meat of farmed obscure puffer ( Takifugu obscurus ) using gas chromatography-mass spectrometry-olfactometry . Journal of Food and Drug Analysis , 22 ( 4 ): 431 - 438 , https://doi.org/10.1016/j.jfda.2014.02.005 https://doi.org/10.1016/j.jfda.2014.02.005 .

Tong Q , Wu L , Jiang T et al . 2016 . Inhibition of endoplasmic reticulum stress-activated IRE1α-TRAF2-caspase-12 apoptotic pathway is involved in the neuroprotective effects of telmisartan in the rotenone rat model of Parkinson’s disease . European Journal of Pharmacology , 776 : 106 - 115 , https://doi.org/10.1016/j.ejphar.2016.02.042 https://doi.org/10.1016/j.ejphar.2016.02.042 .

Tretter L , Patocs A , Chinopoulos C . 2016 . Succinate, an intermediate in metabolism, signal transduction, ROS, hypoxia, and tumorigenesis . Biochimica et Biophysica Acta (BBA)-Bioenergetics , 1857 ( 8 ): 1086 - 1101 , https://doi.org/10.1016/j.bbabio.2016.03.012 https://doi.org/10.1016/j.bbabio.2016.03.012 .

Varticovski L , Stavreva D A , McGowan A et al . 2022 . Endocrine disruptors of sex hormone activities . Molecular and Cellular Endocrinology , 539 : 111415 , https://doi.org/10.1016/j.mce.2021.111415 https://doi.org/10.1016/j.mce.2021.111415 .

Wang L X , Zheng M M , Zhang S P et al . 2019a . Roles of mtDNA damage and disordered Ca 2+ homeostasis in the joint toxicities of cadmium and BDE209 . Ecotoxicology and Environmental Safety , 186 : 109767 , https://doi.org/10.1016/j.ecoenv.2019.109767 https://doi.org/10.1016/j.ecoenv.2019.109767 .

Wang T , Wen X , Hu Y D et al . 2019b . Copper nanoparticles induced oxidation stress, cell apoptosis and immune response in the liver of juvenile Takifugu fasciatus . Fish & Shellfish Immunology , 84 : 648 - 655 , https://doi.org/10.1016/j.fsi.2018.10.053 https://doi.org/10.1016/j.fsi.2018.10.053 .

Wang X , Shen X B , Chen L et al . 2021 . Hepatic oxidative damage and Nrf2 pathway protein changes in rats following long-term manganese exposure . Toxicology and Industrial Health , 37 ( 5 ): 251 - 259 , https://doi.‍org/10.1177/0748233721993311 https://doi.‍org/10.1177/0748233721993311 . https://do 10.1177/0748233721993311 http://dx.doi.org/10.1177/0748233721993311

Wen B , Jin S R , Chen Z Z et al . 2018a . Single and combined effects of microplastics and cadmium on the cadmium accumulation, antioxidant defence and innate immunity of the discus fish ( Symphysodon aequifasciatus ) . Environmental Pollution , 243 : 462 - 471 , https://doi.org/10.1016/j.envpol.2018.09.029 https://doi.org/10.1016/j.envpol.2018.09.029 .

Wen X , Wang D , Li X R et al . 2018b . Differential expression of two Piwil orthologs during embryonic and gonadal development in pufferfish, Takifugu fasciatus . Comparative Biochemistry and Physiology Part B: Biochemistry and Molecular Biology , 219 - 220 : 44 - 51 , https://doi.org/10.1016/j.cbpb.2018.03.005 https://doi.org/10.1016/j.cbpb.2018.03.005 .

Wilkins H M , Marquardt K , Lash L H et al . 2012 . Bcl-2 is a novel interacting partner for the 2-oxoglutarate carrier and a key regulator of mitochondrial glutathione . Free Radical Biology and Medicine , 52 ( 2 ): 410 - 419 , https://doi.org/10.1016/j.freeradbiomed.2011.10.495 https://doi.org/10.1016/j.freeradbiomed.2011.10.495 .

Wu J Y , Henning P , Sjögren K et al . 2019 . The androgen receptor is required for maintenance of bone mass in adult male mice . Molecular and Cellular Endocrinology , 479 : 159 - 169 , https://doi.org/10.1016/j.mce.2018.10.008 https://doi.org/10.1016/j.mce.2018.10.008 .

Zeng M C , Sang W H , Chen S et al . 2017 . 4-PBA inhibits LPS-induced inflammation through regulating ER stress and autophagy in acute lung injury models . Toxicology Letters , 271 : 26 - 37 , https://doi.org/10.1016/j.toxlet.2017.02.023 https://doi.org/10.1016/j.toxlet.2017.02.023 .

Zhang Y B , Wang J , Lu L et al . 2020 . Genotoxic biomarkers and histological changes in marine medaka ( Oryzias melastigma ) exposed to 17α-ethynylestradiol and 17β-trenbolone . Marine Pollution Bulletin , 150 : 110601 , https://doi.org/10.1016/j.marpolbul.2019.110601 https://doi.org/10.1016/j.marpolbul.2019.110601 .

Zheng Y , Chen J Z , Liu Y et al . 2016 . Molecular mechanism of endocrine system impairment by 17α- methyltestosterone in gynogenic Pengze crucian carp offspring . Ecotoxicology and Environmental Safety , 128 : 143 - 152 , https://doi.org/10.1016/j.ecoenv.2015.11.034 https://doi.org/10.1016/j.ecoenv.2015.11.034 .

Zhu Y J , Fan Q D , Mao H L et al . 2013 . GRP78 from grass carp ( Ctenopharyngodon idella ) provides cytoplasm protection against thermal and Pb 2+ stress . Fish & Shellfish Immunology , 34 ( 2 ): 617 - 622 , https://doi.org/10.1016/j.fsi.2012.12.005 https://doi.org/10.1016/j.fsi.2012.12.005 .

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17α-methyltestosterone induced hepatocyte apoptosis through endoplasmic reticulum stress in Takifugu fasciatus

17α-methyltestosterone induced hepatocyte apoptosis through endoplasmic reticulum stress in Takifugu fasciatus

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Abstract

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Keywords

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