Di (2-ethylhexyl) phthalate-induced reproductive toxicity involved in dna damage-dependent oocyte apoptosis and oxidative stress in Caenorhabditis elegans

Di(2-ethylhexyl)phthalate (DEHP) is a typical endocrine-disrupting chemical and reproductive toxicant. Although previous studies have attempted to describe the mechanism by which DEHP exposure results in reproductive dysfunction, few studies focused on puberty, a critical period of reproductive development, and the increased susceptibility to injury in adolescents. To elucidate the mechanism underpinning the testicular effects of DEHP in puberty, we sought to investigate the JAZF1/TR4 pathway in the testes of pubertal rats. Specifically, we focused on the role of the JAZF1/TR4 pathway in male reproduction, including the genes JAZF1, TR4, Sperm 1, and Cyclin A1. In the present study, rats were exposed to increasing concentrations of DEHP (0, 250, 500, and 1000 mg/kg/day) by oral gavages for 30 days. Then we assayed testicular zinc and oxidative stress levels. Our results indicated that DEHP exposure could lead to oxidative stress and decrease the contents of testicular zinc. Additionally, significant morphological changes and cell apoptosis were observed in testes exposed to DEHP, as identified by hematoxylin and eosin staining and the terminal deoxynucleotidyl transferase-mediated nick and labeling assay. By measuring the expression levels of the above relevant genes by qPCR, we found the DEHP-induced increased expression of JAZF1 and decreased expression of TR4, Sperm 1, and Cyclin A1. Therefore, we have demonstrated that in vivo exposure to DEHP might induce reproductive toxicity in pubertal male rats through the JAZF1/TR4 pathway and oxidative stress.

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Di(2-ethylhexyl) phthalate induced reproductive toxicity involved in DNA damage-dependent oocyte apoptosis using alternative Caenorhabditis elegans model

Toxicology Letters ◽

10.1016/j.toxlet.2016.06.1338 ◽

2016 ◽

Vol 258 ◽

pp. S70-S71 ◽

Cited By ~ 1

Author(s):

R. Liu ◽

Z. Jian ◽

D. Yang ◽

Y. Pu ◽

L. Yin

Keyword(s):

Dna Damage ◽

Caenorhabditis Elegans ◽

Reproductive Toxicity ◽

Ethylhexyl Phthalate

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Phthalates and Alternative Plasticizers Differentially affect Phenotypic Parameters in Gonadal Somatic and Germ Cell Lines

Biology of Reproduction ◽

10.1093/biolre/ioab216 ◽

2021 ◽

Author(s):

Abishankari Rajkumar ◽

Trang Luu ◽

Marc A Beal ◽

Tara S Barton-Maclaren ◽

Barbara F Hales ◽

...

Keyword(s):

Oxidative Stress ◽

Cell Line ◽

Cell Lines ◽

Lipid Droplet ◽

Reproductive Toxicity ◽

Mitochondrial Activity ◽

Steroidogenic Cell ◽

Ethylhexyl Phthalate ◽

And Oxidative Stress ◽

Sertoli Cell Line

Abstract The developmental and reproductive toxicity associated with exposure to phthalates has motivated a search for alternatives. However, there is limited knowledge regarding the adverse effects of some of these chemicals. We used high-content imaging to compare the effects of mono (2-ethylhexyl) phthalate (MEHP) with six alternative plasticizers: di-2-ethylhexyl terephthalate (DEHTP); diisononyl-phthalate (DINP); di-isononylcyclohexane-1,2-dicarboxylate (DINCH); 2-ethylhexyl adipate (DEHA); 2,2,4-trimethyl 1,3-pentanediol diisobutyrate (TXIB) and di-iso-decyl-adipate (DIDA). A male germ spermatogonial cell line (C18-4), a Sertoli cell line (TM4) and two steroidogenic cell lines (MA-10 Leydig and KGN granulosa) were exposed for 48h to each chemical (0.001-100 μM). Cell images were analyzed to assess cytotoxicity and effects on phenotypic endpoints. Only MEHP (100 μM) was cytotoxic and only in C18-4 cells. However, several plasticizers had distinct phenotypic effects in all four cell lines. DINP increased Calcein intensity in C18-4 cells, whereas DIDA induced oxidative stress. In TM4 cells, MEHP, and DINCH affected lipid droplet numbers, while DEHTP and DINCH increased oxidative stress. In MA-10 cells, MEHP increased lipid droplet areas and oxidative stress; DINP decreased the number of lysosomes, while DINP, DEHA and DIDA altered mitochondrial activity. In KGN cells, MEHP, DINP and DINCH increased the number of lipid droplets, whereas DINP decreased the number of lysosomes, increased oxidative stress and affected mitochondria. The Toxicological Priority Index (ToxPi) provided a visual illustration of the cell line specificity of the effects on phenotypic parameters. The lowest administered equivalent doses were observed for MEHP. We propose that this approach may assist in screening alternative plasticizers.

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