Kinetics of selected di-n-butyl phthalate metabolites and fetal testosterone following repeated and single administration in pregnant rats

Clewell, Rebecca A.; Kremer, John J.; Williams, Carla C.; Campbell, Jerry L.; Sochaski, Mark A.; Andersen, Melvin E.; Borghoff, Susan J.

doi:10.1016/j.tox.2008.10.010

Cited by 30 publications

(17 citation statements)

References 38 publications

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“…Whether this involves altered Leydig cell numbers, function, or altered hypothalamic-pituitary activity is under investigation. Other studies (65) also suggest that similar doses of another phthalate may have positive effects on postnatal Leydig cell function, and a recent study has shown that even in fetal life (e21.5), exposure to DBP 100 mg/kg may cause a rebound increase (at 48 h) in ITT levels after initially causing suppression (66). These observations suggest that phthalate effects on Leydig cell function in rats may not always be negative.…”

mentioning

confidence: 84%

Glucocorticoids Amplify Dibutyl Phthalate-Induced Disruption of Testosterone Production and Male Reproductive Development

et al. 2009

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Common male reproductive abnormalities including cryptorchidism, hypospadias, and low sperm counts may comprise a testicular dysgenesis syndrome (TDS), resulting from fetal testis dysfunction during a critical developmental period involving reduced androgen production/action. The recent increase in TDS prevalence suggests environmental/lifestyle factors may be etiologically important. The developing fetus is exposed to multimodal challenges, and we hypothesized that exposure to a combination of factors rather than single agents may be important in the pathogenesis of TDS. We experimentally induced fetal testis dysfunction in rats via treatment of pregnant females daily from embryonic day (e) 13.5 to e21.5 with vehicle, 100 or 500 mg/kg . d dibutyl phthalate (DBP), 0.1 mg/kg . d dexamethasone (Dex), or a combination of DBP + Dex. In adulthood, penile length/normality, testis weight/descent, prostate weight, and plasma testosterone levels were measured plus anogenital distance (AGD) as a measure of androgen action within the masculinization programming window. Intratesticular testosterone and steroidogenic enzyme gene expression were measured in fetal testes at e17.5. High-dose DBP reduced fetal intratesticular testosterone and steroidogenic gene expression; induced mild hypospadias (31%) and cryptorchidism (53%); and reduced penile length, AGD, and testis and prostate weight in adulthood. Dex alone had no effect except to reduce birth weight but amplified the adverse effects of 500 mg/kg . d DBP and exacerbated the effects of 100 mg/kg . d DBP. All adverse effects were highly correlated to AGD, emphasizing the etiological importance of the masculinization programming window. These findings suggest that exposure to common environmental chemicals in combination with, for example, maternal stress, may increase the risk of common male reproductive abnormalities, with implications for human populations.

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confidence: 84%

Glucocorticoids Amplify Dibutyl Phthalate-Induced Disruption of Testosterone Production and Male Reproductive Development

et al. 2009

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“…Clewell et al found a concentration of 100µM of MBP (the active metabolite of DBP) in fetal testes approximately 1 hour after administration of 500mg/kg DBP to pregnant Dams. This was followed by a peak of 150µM after 2 hours [45]. By comparison, the in vitro exposure to cells in the current study was to 100µM of parent compound.…”

Section: Discussionmentioning

confidence: 93%

Comparison of toxicogenomic responses to phthalate ester exposure in an organotypic testis co-culture model and responses observed in vivo

Harris

Hermsen

et al. 2015

Reproductive Toxicology

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We have developed a three-dimensional testicular co-culture system (3D-TCS) which mimics in vivo testes. In this study, transcriptomic responses to phthalate esters (PE’s) were compared in the 3D-TCS with responses in rat testes in vivo. Microarray data from the 3D-TCS and from in vivo testes were used to compare changes in gene expression patterns after exposure to developmentally toxic (DTPE) or developmentally non-toxic (DNTPE) phthalate esters. DTPE treatments clustered separately from DNTPE treatments based on principle components analysis both in vitro and in vivo. Pathway analysis using GO-Elite software showed that terms relating to steroid metabolism or reproductive development were enriched both in vitro and in vivo after DTPE exposure. Processes such as cell cycle, cell proliferation and apoptosis were enriched for DTPE treatments in vitro, but not in vivo. Based on these analyses we concluded that transcriptomic responses in the 3D-TCS reflect key aspects of in vivo phthalate toxicity.

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“…PA, p-Tol, BA and p-CBA) at relatively high concentrations. Among them, PA is known as reproductive and developmental toxicants for animals and suspected endocrine disruptors for humans [10,30,31]. p-Tol and other two benzoic compounds solvents were also reported to affect the sperm viability and the function of accessory gonad [13].…”

Section: Discussionmentioning

confidence: 99%

Toxicity of purified terephthalic acid manufacturing wastewater on reproductive system of male mice (Mus musculus)

Zhang

Sun²,

Zhang

et al. 2010

Journal of Hazardous Materials

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Kinetics of selected di-n-butyl phthalate metabolites and fetal testosterone following repeated and single administration in pregnant rats

Cited by 30 publications

References 38 publications

Glucocorticoids Amplify Dibutyl Phthalate-Induced Disruption of Testosterone Production and Male Reproductive Development

Glucocorticoids Amplify Dibutyl Phthalate-Induced Disruption of Testosterone Production and Male Reproductive Development

Comparison of toxicogenomic responses to phthalate ester exposure in an organotypic testis co-culture model and responses observed in vivo

Toxicity of purified terephthalic acid manufacturing wastewater on reproductive system of male mice (Mus musculus)

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