Di-(2-ethylhexyl) phthalate induces testicular endoplasmic reticulum stress and germ cell apoptosis in adolescent mice
- 7 January 2021
- journal article
- research article
- Published by Springer Science and Business Media LLC in Environmental Science and Pollution Research
- Vol. 28 (17), 21696-21705
- https://doi.org/10.1007/s11356-020-12210-z
Abstract
Di-(2-ethylhexyl) phthalate (DEHP) is a male reproductive toxicant. This research is aimed at investigating the effect of pubertal DEHP exposure on testicular endoplasmic reticulum (ER) stress and germ cell apoptosis. Five-week-old male mice were orally administered with DEHP (0, 0.5, 50, or 500 mg/kg/day) for 35 days. Testis weight and sperm count were reduced in mice exposed to 500 mg/kg/day DEHP. The number of seminiferous tubules in stages VII–VIII, mature seminiferous tubules, was reduced and the number of seminiferous tubules in stages IX–XII, immature seminiferous tubules, was elevated in mice treated with 500 mg/kg/day DEHP. Numerous apoptotic germ cells were observed in mouse seminiferous tubules exposed to 50 and 500 mg/kg/day DEHP. Moreover, cleaved caspase-3 was elevated in mouse testes exposed to 500 mg/kg/day DEHP. In addition, Bcl-2 was reduced and Bax/Bcl-2 was elevated in mouse testes exposed to 500 mg/kg/day DEHP. Additional experiment showed that GRP78, an ER molecular chaperone, was downregulated in mouse testes exposed to 500 mg/kg/day DEHP. Testicular p-IRE-1α, p-JNK, and CHOP, three markers of ER stress, were upregulated in mice exposed to 500 mg/kg/day DEHP. These results suggest that pubertal exposure to high doses of DEHP induces germ cell apoptosis partially through initiating ER stress in testes.Keywords
Funding Information
- National Natural Science Foundation of China (91743105, 81930093)
- Natural Science Foundation of Anhui Province (1908085QH367)
This publication has 48 references indexed in Scilit:
- Acute 1-NP exposure induces inflammatory responses through activating various inflammatory signaling pathways in mouse lungs and human A549 cellsEcotoxicology and Environmental Safety, 2020
- Butylated hydroxyanisole induces testicular dysfunction in mouse testis cells by dysregulating calcium homeostasis and stimulating endoplasmic reticulum stressScience of The Total Environment, 2020
- Phthalate esters in biota, air and water in an agricultural area of western China, with emphasis on bioaccumulation and human exposureScience of The Total Environment, 2020
- The C/EBP Homologous Protein (CHOP) Transcription Factor Functions in Endoplasmic Reticulum Stress-Induced Apoptosis and Microbial InfectionFrontiers in Immunology, 2019
- The Unfolded Protein Response and Cell Fate ControlMolecular Cell, 2018
- Phthalate esters in the environment: A critical review of their occurrence, biodegradation, and removal during wastewater treatment processesScience of The Total Environment, 2016
- Leaching of the plasticizer di(2-ethylhexyl)phthalate (DEHP) from plastic containers and the question of human exposureApplied Microbiology and Biotechnology, 2014
- Transgenerational Effects of Di-(2-ethylhexyl) Phthalate on Testicular Germ Cell Associations and Spermatogonial Stem Cells in Mice1Biology of Reproduction, 2013
- Crosstalk Between Endoplasmic Reticulum Stress and Mitochondrial Pathway Mediates Cadmium-Induced Germ Cell Apoptosis in TestesToxicological Sciences, 2011
- Arsenic Trioxide Impairs Spermatogenesis via Reducing Gene Expression Levels in Testosterone Synthesis PathwayChemical Research in Toxicology, 2008