Species differences in the testicular toxicity of phthalate esters

Gray, Tim J.B.; Rowland, Ian; Foster, Paul M.D.; Gangolli, S.D.

doi:10.1016/0378-4274(82)90119-9

Cited by 130 publications

(64 citation statements)

References 18 publications

Supporting

Mentioning

Contrasting

Unclassified

Order By: Relevance

“…In this present study, there was no difference between the mean body weight and testicular weight. Elsewhere, Gray et al (1982) observed a decrease in testicular weight. Embryonic exposure to xenoestrogens produced a reduction in the growth of the cloacal gland at sexual maturity in male Japanese quail (Adkins, 1979;Halldin et al, 1999;Halldin et al, 2003).…”

Section: Effects On Histopathologymentioning

confidence: 95%

“…Consequently, intermediate stages of crowing development could be associated with reduced testosterone production stemming from social stimulation (Groothuis). Several reports (Gray et al, 1982;Barlow et al, 2003) have indicated that testosterone effects on germinal tissue are in fact, responsible for the observed decrease in seminiferous tubular height and the corresponding decrease in testis weight. In this present study, there was no difference between the mean body weight and testicular weight.…”

Section: Effects On Histopathologymentioning

confidence: 99%

See 1 more Smart Citation

The effects on steroidogenesis and histopathology of adult male Japanese quails (Coturnix coturnix japonica) testis following pre-pubertal exposure to di(n-butyl) phthalate (DBP)

Bello

Madekurozwa

Groenewald

et al. 2014

Comparative Biochemistry and Physiology Part C: Toxicology &

View full text Add to dashboard Cite

Keywords:Di-(n-butyl) phthalate Leydig cell Steroidogenesis Male Japanese quails Endocrine disruptionIn the present study, we have investigated the effects of 30-day dietary (pre-pubertal) exposure to different doses (0 (control), 1, 10, 50, 200 and 400 mg/kg bodyweight/day) of di(n-butyl) phthalate (DBP) on Leydig cells of adult male Japanese quails by quantifying the transcript levels for P450 side-chain cleavage (p450scc), P450c17 (CYP17), and 3β-and 17β-hydroxysteroid dehydrogenase (hsd) using quantitative (real-time) poly-merase chain reaction (qRT-PCR). In addition, the plasma testosterone levels were analysed using radioimmuno-assay (RIA) and testis was examined for evidence of gross pathology and histopathology. Our data showed that pre-pubertal exposure to DBP produced alterations in testicular architecture as evident by poorly developed or misshaped testis, and altered spermatogenesis due to tubular degeneration and atrophy of seminiferous tubules especially in the high DBP dose (200 and 400 mg/ kg) treated groups. In addition, DBP altered several key en-zymes involved in testicular steroidogenesis pathways in an apparent dose-dependent manner. For example, bi-phasic effects of DBP were observed for P450scc and 3β-hsd mRNA, that were generally increasing at low dose 10 mg/kg, and thereafter, an apparent dose-dependent decrease between 50 and 400 mg/kg. The steroidogenic acute regulatory (StAR) protein was at the lowest detectable limits and therefore not quantifiable. These effects did not parallel the non-significant changes observed for plasma testosterone levels. The present data is consis-tent with previous reports showing that DBP modulates Leydig cell steroidogenesis in several species, with a po-tential negative effect on reproduction in those avian species that are vulnerable to endocrine disrupting chemicals.

show abstract

Section: Effects On Histopathologymentioning

confidence: 95%

Section: Effects On Histopathologymentioning

confidence: 99%

The effects on steroidogenesis and histopathology of adult male Japanese quails (Coturnix coturnix japonica) testis following pre-pubertal exposure to di(n-butyl) phthalate (DBP)

Bello

Madekurozwa

Groenewald

et al. 2014

Comparative Biochemistry and Physiology Part C: Toxicology &

View full text Add to dashboard Cite

show abstract

“…Phthalate diesters are initially metabolized to the corresponding monoester and alcohol moieties. The testicular lesion can be reproduced by administration of the monoester but not by the alcohol (7)(8). Whether further metabolism of the monoester (9) is required has not yet been established.…”

Section: Introductionmentioning

confidence: 99%

“…Mice, guinea pigs, and ferrets are also susceptible to the induction of testicular injury by phthalate esters, but Syrian hamsters are comparatively resistant (8,10). The lesion is similar in all susceptible species, involving early detachment of spermatocytes and spermatids from the seminiferous epithelium, but little is known of the mechanisms underlying this effect.…”

Section: Introductionmentioning

confidence: 99%

Aspects of the testicular toxicity of phthalate esters.

Gray¹,

Gangolli²

1986

Environ Health Perspect

View full text Add to dashboard Cite

Di(2-ethylhexyl) phthalate (DEHP) produced seminiferous tubular atrophy and reductions in seminal vesicle and prostate weight in 4-week-old, but not in 15-week-old rats. Di-n-pentyl phthalate (DPP) did produce atrophy in the older rats but this developed more slowly than in young animals. Coadministration of testosterone or gonadotrophins did not protect against phthalate-induced testicular toxicity but did partly reverse the depression of seminal vesicle and prostate weight. Secretion of seminiferous tubule fluid and androgen binding protein by the Sertoli cells was markedly suppressed within 1 hr of a dose of DPP or mono-2-ethylhexyl phthalate (MEHP) in immature rats. This occurred less rapidly in mature rats.[14C]Mono-npentyl phthalate and [14C]MEHP penetrated the blood testis barrier only to a very limited extent. These findings and the early morphological changes in the Sertoli cells produced by DPP suggest that phthalate esters may act initially to cause Sertoli cell injury, the subsequent loss of germ cells occurring as a consequence of this.Some features of the testicular lesion could be reproduced in primary cocultures of rat Sertoli and germ cells. Structure activity studies with a range of phthalate monoesters showed good agreement between the induction of germ cell detachment in culture and testicular toxicity in vivo. Three metabolites of MEHP (metabolites V, VI, and IX) were much less toxic in culture than MEHP itself, suggesting that the latter may be the active testicular toxin from DEHP.

show abstract

“…The most prominent effect of DBP is testicular atrophy (Oishi & Hiraga 1980, Gray et al 1982. To date, several mechanisms have been proposed to explain the induction of testicular atrophy by DBP, such as the depletion of zinc (Oishi & Hiraga 1980), increased oxidative damage of proteins, lipids, and DNA (Fukuoka et al 1990), alteration of vimentin cytoskeleton organization (Kleymenova et al 2005), or membrane alteration in Sertoli cells leading to sloughing of spermatogenic cells (Kleymenova et al 2005).…”

Section: Introductionmentioning

confidence: 99%

Induction of spermatogenic cell apoptosis in prepubertal rat testes irrespective of testicular steroidogenesis: a possible estrogenic effect of di(n-butyl) phthalate

Alam

Ohsako²,

Matsuwaki³

et al. 2010

Reproduction

View full text Add to dashboard Cite

Although di(n-butyl) phthalate (DBP), a suspected endocrine disruptor, induces testicular atrophy in prepubertal male rats, whether it exerts estrogenic activity in vivo remains a matter of debate. In the present study, we explored the estrogenic potency of DBP using 3-week-old male rats, and then examined the relationship between estrogen-induced spermatogenic cell apoptosis and testicular steroidogenesis. Daily exposure to DBP for 7 days caused testicular atrophy due to loss of spermatogenic cells, whereas testicular steroidogenesis was almost the same with the control values. A single exposure of DBP decreased testicular steroidogenesis in addition to decreasing the level of serum LH at 3 h after DBP treatment, with an extremely high incidence of apoptotic spermatogenic cells at 6 h after administration. To elucidate the estrogenic activity of DBP, we carried out an inhibition study using pure antiestrogen ICI 182,780 (ICI) in a model of spermatogenic cell apoptosis induced by DBP or estradial-3-benzoate (EB). Although both the DBP-and EB-treated groups showed a significant increase in spermatogenic cell apoptosis, ICI pretreatment significantly decreased the number of apoptotic spermatogenic cells in these two groups. In contrast, testicular steroidogenesis and serum FSH were significantly reduced in all the treated groups, even in the DBPCICI and EBCICI groups. Taken together, these findings led us to conclude that estrogenic compounds such as DBP and EB induce spermatogenic cell apoptosis in prepubertal rats, probably by activating estrogen receptors in testis, and that reduction in testicular steroidogenic function induced by estrogenic compounds is not associated with spermatogenic cell apoptosis.

show abstract

Species differences in the testicular toxicity of phthalate esters

Cited by 130 publications

References 18 publications

The effects on steroidogenesis and histopathology of adult male Japanese quails (Coturnix coturnix japonica) testis following pre-pubertal exposure to di(n-butyl) phthalate (DBP)

The effects on steroidogenesis and histopathology of adult male Japanese quails (Coturnix coturnix japonica) testis following pre-pubertal exposure to di(n-butyl) phthalate (DBP)

Aspects of the testicular toxicity of phthalate esters.

Induction of spermatogenic cell apoptosis in prepubertal rat testes irrespective of testicular steroidogenesis: a possible estrogenic effect of di(n-butyl) phthalate

Contact Info

Product

Resources

About