Testicular Atrophy Produced by Phthalate Esters

Gray, Tim J.B.; Butterworth, K.R.

doi:10.1007/978-3-642-67729-8_106

Cited by 117 publications

(49 citation statements)

References 4 publications

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“…In this study, 4 time durations (1,3,6, and 9 hr) and 5 MEHP concentrations (control, 1 Â 10 À6 , 1 Â 10 À3 , 1, and 100 nmol.ml À1 ) were designed. The harvesting was carried out at 1, 3, 6, and 9 hr after administration.…”

Section: Testicular Tissue Culturementioning

confidence: 99%

Effects of Mono(2-ethylhexyl) Phthalate (MEHP) on Testes in Rats In Vitro

Andriana¹,

Tay²,

Tachiwana³

et al. 2004

Okajimas Folia Anat. Jpn.

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Summary: The phthalate esters have been used as plasticizers for various plastic products, and their testicular toxicity has been reported. In this study, the effects of mono(2-ethylhexyl) phthalate (MEHP), one of the phthalate esters, on prepubertal rat testes in vitro were examined. The testes of 20-day-old Sprague Dawley (SD) rats were cut into smaller pieces and seeded in medium, and then the specimens were obtained for light and transmission electron microscopic observations. As a result, at 1 hr after exposure to MEHP, TUNEL-positive spermatogenic cells were identified, and they gradually increased in number in time-and dose-dependent manners. Ultrastructurally, apoptotic spermatogenic cells (characterized with chromatin condensation, cytoplasm shrinkage without membrane rupture, still-functioning cell organelles, and packed cell contents in membrane-bounded bodies), necrotic spermatogenic cells (characterized with swollen and ruptured mitochondria, plasma membrane lysis, spilt cell contents, and chromatin clumps), apoptotic Sertoli cells (highly condensed nuclei and nuclear membrane lysis) and necrotic Sertoli cells (marginated chromatins along the nuclear membrane, some swollen and ruptured cell organelles, e.g. mitochondria) could be identified. Conclusively, based on transmission electron microscopic observations, MEHP treatment may affect spermatogenic cells, and lead them to necrosis. Thus, testicular tissue cultures and cell cultures are of advantageous for screening testicular toxicity of chemicals.Phthalic acid esters have already been proved as a potential compound to reduce fertility, and induce testicular atrophy in laboratory animals (Thomas and Thomas, 1984). One of the most widely-studied male reproductive toxicants in rats is di(2-ethylhexyl) phthalate (DEHP) (Richburg and Boekelheide, 1996). Albro et al. (1973), Rowland et al. (1977), Lake et al. (1977), and Thomas and Thomas (1984) have reported that after oral administration, phthalates are rapidly hydrolyzed in gut and other tissues by nonspecific esterases to produce the corresponding monoester. Pollack et al. (1985) also have reported that mono(2-ethylhexyl) phthalate (MEHP) is one of the most potently occurring monoester and an ultimate testicular toxic metabolite.Recently, research interest tends have changed from DEHP to MEHP. Although Richburg andBoekelheide (1996), andSuominen et al. (2003) have conducted MEHP experiments using laboratory animals (in vivo), there is still lack of MEHP testing using the testicular tissue culture (in vitro). The tissue culture is advantageous to clarify the direct effects of chemicals on target cells. Therefore, in this study, prepubertal Sprague-Dawley (SD) rat testes were used to ascertain the effects of MEHP on rat testicular tissue culture (in vitro), with specific focus on the morphological alterations of Sertoli and spermatogenic cells. Materials and MethodsBiochemical effects of mono(2-ethylhexyl) phthalate (MEHP) on Sertoli and spermatogenic cells in prepubertal male Sprague-Dawley rats (at

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Section: Testicular Tissue Culturementioning

confidence: 99%

Effects of Mono(2-ethylhexyl) Phthalate (MEHP) on Testes in Rats In Vitro

Andriana¹,

Tay²,

Tachiwana³

et al. 2004

Okajimas Folia Anat. Jpn.

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“…Gray and Butterworth (37) showed in a 90-day toxicity study in rats that DEHP caused testicular atrophy. Sem- iniferous tubular atrophy, comprising a loss of spermatids and spermatocytes, occurred when young (4-week-old) rats were given 10 daily doses of DEHP Somewhat older rats (e.g., 10-and 15-week-old) showed less testicular damage or none at all.…”

Section: Testicular Effectsmentioning

confidence: 99%

Effects of Phthalic Acid Esters (PAEs) on the Neonate and Aspects of Teratogenic Actions

Thomas¹,

Wienckowski²,

Gillies³

et al. 1986

Environmental Health Perspectives

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A review of the literature reveals that several different phthalic acid esters (PAEs) are capable of causing testicular damage. Phthalate-induced zinc deficiency is consistent with germinal epithelial damage. Among experimental animals, mice perhaps show the greatest sensitivity to phthalate-induced terata, but high doses/exposure are required. Little toxicologic information is available with regard to phthalate-induced effects upon the neonate.

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“…Such effects as testicular atrophy (1) and peroxisome proliferation in rodents (2) are also seen on administration of the primary hydrolysis products of phthalate esters (3)(4)(5). Effects produced by, e.g.…”

Section: Introductionmentioning

confidence: 96%

Absorption, Metabolism, and Excretion of Di(2-Ethylhexyl) Phthalate by Rats and Mice

Albro¹

1986

Environmental Health Perspectives

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There is convincing evidence in the literature that most of the adverse biological effects of phthalate diesters are actually effects of metabolites rather than of the parent compounds. If so, the dramatic species differences in endpoint metabolic profiles make it essential that metabolism of phthalates be understood in detail, including the factors that may alter the metabolism. A metabolic pathway for phthalates having saturated alkyl groups has been postulated based on identification of metabolites produced in vivo and excreted in urine. The first few steps in the postulated pathway have been confirmed in vitro using enzymatically active preparations from rats and mice; some details of the nature of these early steps have been learned. Although some information concerning later steps is available, much remains to be learned in this area. Species differences are postulated to involve kinetics of several biochemical and physiological events acting in concert or competition. Among these interacting factors are competition of at least three enzymes for phthalate monoesters as substrate, relative kidney clearance rates for different metabolites, relative Km values of oxidative enzymes for the same precursors in different species, and relative equilibria between glucuronide formation and hydrolysis.

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Testicular Atrophy Produced by Phthalate Esters

Cited by 117 publications

References 4 publications

Effects of Mono(2-ethylhexyl) Phthalate (MEHP) on Testes in Rats In Vitro

Effects of Mono(2-ethylhexyl) Phthalate (MEHP) on Testes in Rats In Vitro

Effects of Phthalic Acid Esters (PAEs) on the Neonate and Aspects of Teratogenic Actions

Absorption, Metabolism, and Excretion of Di(2-Ethylhexyl) Phthalate by Rats and Mice

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