Light and electron microscopic evidence of tri-o-cresyl phosphate (TOCP)-mediated testicular toxicity in Fischer 344 rats

Somkuti, Stephen G.; Lapadula, Daniel M.; Chapin, Robert E.; Abou‐Donia, Mohamed B.

doi:10.1016/0041-008x(91)90328-c

Cited by 38 publications

(22 citation statements)

References 29 publications

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“…Since testicular sperms received sufficient proteins, pyruvic acid and lactic acid originating from the mature Sertoli cells at 12 weeks, they were considered not to become HS. This notion could be supported by the fact that HS decreased to about 10% and almost zero in urine and the epididymis, respectively, at 12 weeks or older, and by the report that the epididymal HS increased in testicular toxicant-injured Sertoli cells (Somkuti et al 1991, Yamamoto et al 1999. In conventional toxicity studies with rats, when maturation was delayed due to illcondition and decreased body weights, HS incidence may be increased only in the treatment groups, especially at an age of around 12 weeks.…”

Section: Discussionsupporting

confidence: 51%

“…Many chemicals have been reported to affect sperm morphology in the epididymis of rats; they include adriamycin (Kato et al 2001), ethyl methanesulphonate (Takagi et al 2000), nitrobenzene (Yamamoto et al 2000), boric acid (Linder et al 1990), gossypol (Swan et al 1990), methyl chloride (Working et al 1985), 1-bromopropane (Ichihara et al 2000) and tri-o-cresyl phosphate (Somkuti et al 1991). Headless sperms (HS) are normally classified as one type of abnormal sperm morphology in a traditional toxicology study with rats (Lock & Soares 1980).…”

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confidence: 99%

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Occurrence of headless sperms in adolescent rat urine

Shimomura¹,

Sakurai²,

Shimada³

et al. 2008

Lab Anim

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SummaryIncreased incidence of headless sperms (HS) was spontaneously observed in the urine of adolescent naïve male SPF/VAF Crl:CD(SD) rats. To clarify the factors contributing to this event, the HS incidence in urine and the epididymis was periodically examined in conjunction with measurements of testis and epididymis weights, motility and morphology of sperms and testosterone, transferrin or follicle-stimulating hormone (FSH) concentrations in serum and/or the testis. The urinary HS incidence was 61%, 69%, 44%, 30%, 14%, 9% and 7% in 100 sperms counted at ages 8, 9, 10, 11, 12, 13 and 14 weeks, respectively; namely, HS peaked at 9 weeks, gradually decreased from 10 weeks and became almost a plateau from 12 weeks onwards. The epididymal HS incidence, which was lower than that in urine, peaked at 8 weeks, decreased from 10 weeks and became almost zero from 12 weeks. By scanning electron microscopy of HS in the epididymis, a narrow gap between the sperm head and neck was clearly seen along with the posterior ring. Concentrations of testicular testosterone and transferrin, a marker for Sertoli cell maturation, reached mature animal levels at 12 weeks. In contrast, no change in serum FSH concentration was seen throughout the study period. These results demonstrate that a marked increase in urinary HS incidence in naïve rats at ages 8-11 weeks would be a physiological phenomenon seen in connection with the process of Sertoli cell maturation.

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Section: Discussionsupporting

confidence: 51%

mentioning

confidence: 99%

Occurrence of headless sperms in adolescent rat urine

Shimomura¹,

Sakurai²,

Shimada³

et al. 2008

Lab Anim

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“…In addition, TOCP had adverse effects on male reproductive system. TOCP can inhibit sperm motility and decrease sperm number in both roosters (Somkuti et al 1987b) and rats (Somkuti et al 1991, Latendresse et al 1994. TOCP can also decrease the fertility index in Swiss (CD-1) mice and lead to decrease in the number of liveborn pups per litter (Chapin et al 1988).…”

Section: Discussionmentioning

confidence: 99%

“…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%

“…It has been reported that TOCP can induce reproductive toxicology (Somkuti et al 1987a(Somkuti et al , 1991, besides neurotoxicity (Craig & Barth 1999, Zhang et al 2007 and immunotoxicity (Foil et al 1980, Brinkerhoff et al 1981 in animals. 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.…”

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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Adhesion and Signaling Proteins Spatiotemporally Associated With Spermiation in the Rat

WINE,

CHAPIN

1999

Journal of Andrology

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Spermiation, the process by which late spermatids separate from the Sertoli cell, is disrupted by a number of toxicants. In this study, we used immunohistochemistry (IHC) to identify some of the proteins associated with the spermatid‐Sertoli junction. We confirmed the presence of tubulin, actin, and vinculin at the luminal edge of the seminiferous tubule, and we determined that paxillin is also present here. In other cell types, these proteins have been reported to colocalize with p integrins. Numerous attempts to identify 0 integrins by IHC and by use of Western blots were unsuccessful. Clear evidence was found for the presence of N‐cadherin and its associated intracellular proteins: β‐catenin, pp120, desmoglein, pp60src, and Csk. In addition, N‐cadherin and desmoglein were found around spermatids retained by the epithelium. From these data and previous literature reports, we propose a hypothetical model for spermatid adhesion and the control of that adhesion, thus providing a framework for hypotheses on the steps involved in the complex process of spermiation in rat testes.

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Light and electron microscopic evidence of tri-o-cresyl phosphate (TOCP)-mediated testicular toxicity in Fischer 344 rats

Cited by 38 publications

References 29 publications

Occurrence of headless sperms in adolescent rat urine

Occurrence of headless sperms in adolescent rat urine

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

Adhesion and Signaling Proteins Spatiotemporally Associated With Spermiation in the Rat

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