Involvement of neuropathy target esterase in tri-ortho-cresyl phosphate-induced testicular spermatogenesis failure and growth inhibition of spermatogonial stem cells in mice

Chen, Jiaxiang; Xu, Linlin; Mei, Jinhong; Yu, Xu-Bo; Kuang, Haibin; Liu, Hongyu; Wu, Yi‐Jun; Wang, Jinglei

doi:10.1016/j.toxlet.2012.03.004

Cited by 34 publications

(35 citation statements)

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“…TOCP, one of the three TCP isomers, has been widely used in the industry (Craig & Barth 1999, Winder & Balouet 2002, Chen et al 2012). TOCP can induce neurotoxicity (Craig & Barth 1999, Zhang et al 2007 and immunotoxicity (Foil et al 1980, Brinkerhoff et al 1981 in animals.…”

Section: Discussionmentioning

confidence: 99%

“…In the current study, we found that TOCP inhibited cell proliferation of rat spermatogonial stem cells in a dose-dependent manner. However, as far as the SH-SY5Y cells are concerned, the viability of the cells can be inhibited by TOCP with a higher concentration or a longer time (Chang et al 2006, Long & Wu 2008, Chen et al 2012.…”

Section: Discussionmentioning

confidence: 99%

“…We also found that saligenin cyclic-o-tolyl phosphate (SCOTP), which was converted from TOCP by cytochrome P450 (CYP450), significantly inhibited viability of mice spermatogonial stem cells (Chen et al 2012). However, inhibition of viability of spermatogonial stem cells might result from decrease in cell proliferation, induction of apoptosis, and autophagy.…”

Section: Introductionmentioning

confidence: 96%

“…TOCP has been shown to decrease sperm density in the cauda epididymis, inhibit testicular enzyme activities, and disrupt the seminiferous epithelium in rats and mice (Somkuti et al 1987a, 1991, Chen et al 2012. However, the precise mechanisms remain to be elusive.…”

Section: Introductionmentioning

confidence: 99%

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Tri-ortho-cresyl phosphate induces autophagy of rat spermatogonial stem cells

Liu¹,

Wang²,

Wei³

et al. 2015

Reproduction

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Tri-ortho-cresyl phosphate (TOCP) has been widely used as plasticizers, plastic softeners, and flame retardants in industry and reported to have a deleterious effect on the male reproductive system in animals besides delayed neurotoxicity. Our preliminary results found that TOCP could disrupt the seminiferous epithelium in the testis and inhibit spermatogenesis, but the precise mechanism is yet to be elucidated. This study shows that TOCP inhibited viability of rat spermatogonial stem cells in a dose-dependent manner. TOCP could not lead to cell cycle arrest in the cells; the mRNA levels of p21, p27, p53, and cyclin D1 in the cells were also not affected by TOCP. Meanwhile, TOCP did not induce apoptosis of rat spermatogonial stem cells. After treatment with TOCP, however, both LC3-II and the ratio of LC3-II/LC3-I were markedly increased; autophagy proteins ATG5 and beclin 1 were also increased after treatment with TOCP, indicating that TOCP could induce autophagy in the cells. Ultrastructural observation under the transmission electron microscopy indicated that autophagic vesicles in the cytoplasm containing extensively degraded organelles such as mitochondria and endoplasmic reticulum increased significantly after the cells were treated with TOCP. In summary, we have shown that TOCP can inhibit viability of rat spermatogonial stem cells and induce autophagy of the cells, without affecting cell cycle and apoptosis.

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Section: Discussionmentioning

confidence: 99%

Section: Discussionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 96%

Section: Introductionmentioning

confidence: 99%

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Tri-ortho-cresyl phosphate induces autophagy of rat spermatogonial stem cells

Liu¹,

Wang²,

Wei³

et al. 2015

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“…Some organophosphates may be involved in inflammation or inflammatory diseases such as asthma (Proskocil et al 2013;Banks and Lein 2012). Neurodegeneration and spermatotoxicity may be additional side effects Chen et al 2012).…”

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confidence: 99%

Monocrotophos in Gandaman village: India school lunch deaths and need for improved toxicity testing

et al. 2013

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Tri‐ortho‐cresyl phosphate (TOCP)‐induced reproductive toxicity involved in placental apoptosis, autophagy and oxidative stress in pregnant mice

Yang

Wang

et al. 2019

Environmental Toxicology

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Tri-ortho-cresyl phosphate (TOCP) has been widely used as plasticizers, and reported causing reproductive toxicity in mammals. However, little is known about the toxic effect on the placenta. In this study, dams were orally administered different doses of TOCP to explore the effect of TOCP on placental development. Results showed that TOCP exposure significantly reduced numbers of implanted embryo, caused atrophy and collapse of ectoplacental cone, and decreased total areas of placenta and numbers of PCNA-positive cells. Expression levels of placental development genes were prominently downregulated in the TOCP-treated groups. Moreover, TOCP administration induced placental apoptosis and autophagy by upregulating P53, Bax, Beclin-1, ratio of LC3 II/LC3 I and Atg5 and downregulating Bcl-2 protein.In addition, TOCP exposure markedly inhibited activities of catalase and superoxide dismutase and increased the production of H 2 O 2 and malondialdehyde. Collectively, these findings suggest that apoptosis, autophagy and oxidative stress may be involved in the TOCP-induced reproductive toxicity. K E Y W O R D S apoptosis, autophagy, oxidative stress, placenta, toxicity, tri-ortho-cresyl phosphate 1 | INTRODUCTION Tri-ortho-cresyl phosphate (TOCP) is the important one of three isomer of tricresyl phosphate (including o-, m-, and p-cresyl). 1 As a plasticizer and organophosphates (OPs) compound, it is widely used in plastics, paint, flame retardant, gasoline additives, solvents, lubricants, and so on. 2,3 In 1930, lots of cases of paralysis were reported in the United States of America due to eating the extract of Jamaica ("jake") contaminated with TOCP, which can produce a delayed neurodegenerative syndrome called OP-induced delayed neuropathy (OPIDN) in human beings and sensitive species. 4,5 Since then, similar symptoms have also occurred in other parts of the world. 6,7 OPIDN is characterized by distal axonal lesions, ataxia, and neuronal degeneration in the spinal cord andthe peripheral nervous systems. 6,8,9 Apart from neurotoxicity, it has been found that TOCP exposure can induce the reproductive toxicology. 1,10 Studies 11,12 have demonstrated that TOCP treatment for 5 or 63 days decreased the motility and density of cauda epididymal sperm and inhibited testicular enzymes activity in a dose-dependent manner and changed sperm morphology in male rats. Chen et al 1,13 found that TOCP suppressed the viability and proliferation of rat spermatogonial stem cells by inducing cell autophagy or inhibiting the neuropathy target esterase.Incubations with TOCP for 48 hours significantly decreased the viability and testosterone secretion of mouse Leydig TM3 cells via the

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Involvement of neuropathy target esterase in tri-ortho-cresyl phosphate-induced testicular spermatogenesis failure and growth inhibition of spermatogonial stem cells in mice

Cited by 34 publications

References 41 publications

Tri-ortho-cresyl phosphate induces autophagy of rat spermatogonial stem cells

Tri-ortho-cresyl phosphate induces autophagy of rat spermatogonial stem cells

Monocrotophos in Gandaman village: India school lunch deaths and need for improved toxicity testing

Tri‐ortho‐cresyl phosphate (TOCP)‐induced reproductive toxicity involved in placental apoptosis, autophagy and oxidative stress in pregnant mice

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