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The plasticizer butyl benzyl phthalate induces genomic changes in rat mammary gland after neonatal/prepubertal exposure.

ABSTRACT: Phthalate esters like n-butyl benzyl phthalate (BBP) are widely used plasticizers. BBP has shown endocrine-disrupting properties, thus having a potential effect on hormone-sensitive tissues. The aim of this study is to determine the effect of neonatal/prepubertal exposure (post-natal days 2-20) to BBP on maturation parameters and on the morphology, proliferative index and genomic signature of the rat mammary gland at different ages of development (21, 35, 50 and 100 days).Here we show that exposure to BBP increased the uterine weight/body weight ratio at 21 days and decreased the body weight at time of vaginal opening. BBP did not induce significant changes on the morphology of the mammary gland, but increased proliferative index in terminal end buds at 35 days and in lobules 1 at several ages. Moreover, BBP had an effect on the genomic profile of the mammary gland mainly at the end of the exposure (21 days), becoming less prominent thereafter. By this age a significant number of genes related to proliferation and differentiation, communication and signal transduction were up-regulated in the glands of the exposed animals.These results suggest that BBP has an effect in the gene expression profile of the mammary gland.

SUBMITTER: Moral R

PROVIDER: S-EPMC2200869 | biostudies-literature | 2007 Dec

REPOSITORIES: biostudies-literature

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The plasticizer butyl benzyl phthalate induces genomic changes in rat mammary gland after neonatal/prepubertal exposure.

Moral Raquel R Wang Richard R Russo Irma H IH Mailo Daniel A DA Lamartiniere Coral A CA Russo Jose J

BMC genomics 20071206

<h4>Background</h4>Phthalate esters like n-butyl benzyl phthalate (BBP) are widely used plasticizers. BBP has shown endocrine-disrupting properties, thus having a potential effect on hormone-sensitive tissues. The aim of this study is to determine the effect of neonatal/prepubertal exposure (post-natal days 2-20) to BBP on maturation parameters and on the morphology, proliferative index and genomic signature of the rat mammary gland at different ages of development (21, 35, 50 and 100 days).<h4> ...[more]

PMID: 18062813

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Project description:BackgroundEnvironmental estrogens are exogenous estrogen-mimicking compounds that can interfere with endogenous endocrine systems. Several of these endocrine disruptors have been shown to alter normal development and influence tumorigenesis in experimental models. N-butyl benzyl phthalate (BBP), a widely used plasticizer, is a well-known endocrine disruptor. The aim of this study was to elucidate the effect of prenatal exposure to BBP on the morphology, proliferative index, and genomic signature of the rat mammary gland at different ages.MethodsIn utero exposure was performed by gavage of pregnant Sprague Dawley CD rats with 120mg or 500mg BBP/kg/day from day 10 post-conception to delivery. Female litters were euthanized at 21, 35, 50 and 100 days. The morphology and proliferative index of the mammary gland were studied from whole mount preparations and BrdU incorporation, respectively. Gene expression profile was assessed by microarrays. Several genes found differentially expressed and related to different functional categories were further validated by real time RT-PCR.ResultsPrenatal exposure of BBP induced delayed vaginal opening and changes in the post-natal mammary gland long after the end of the treatment, mainly by 35 days of age. Exposure to the high dose resulted in modifications in architecture and proliferative index of the mammary gland, mostly affecting the undifferentiated terminal end buds. Moreover, the expression profiles of this gland in the exposed rats were modified in a dose-dependent fashion. Analysis of functional categories showed that modified genes were related to immune function, cell signaling, proliferation and differentiation, or metabolism.ConclusionsOur data suggest that in utero exposure to BBP induced a delayed pubertal onset and modified morphology of the mammary gland. These alterations were accompanied by modifications in gene expression previously associated with an increased susceptibility to carcinogenesis.

Project description:Phthalate diesters are extensively used as plasticizers in manufacturing plastic materials; however, because of their estrogenic properties, these chemicals have emerged as a global threat to human health. The present study investigated the course of degradation of a widely used plasticizer, benzyl butyl phthalate (BBP), by the bacterium PAE-6, belonging to the genus Rhodococcus. The metabolism of BBP, possessing structurally dissimilar side chains, was evaluated biochemically using a combination of respirometric, chromatographic, enzymatic, and mass-spectrometric analyses, depicting pathways of degradation. Consequently, the biochemical observations were corroborated by identifying possible catabolic genes from whole-genome analysis, and the involvement of inducible specific esterases and other degradative enzymes was validated by transcriptomic, reverse transcription-quantitative PCR (RT-qPCR) and proteomic analyses. Nonetheless, phthalic acid (PA), an intermediate of BBP, could not be efficiently metabolized by strain PAE-6, although the genome contains a PA-degrading gene cluster. This deficiency of complete degradation of BBP by strain PAE-6 was effectively managed by using a coculture of strains PAE-6 and PAE-2. The latter was identified as a Paenarthrobacter strain which can efficiently utilize PA. Based on sequence analysis of the PA-degrading gene cluster in strain PAE-6, it appeared that the alpha subunit of the multicomponent phthalate 3,4-dioxygenase harbors a number of altered residues in the multiple sequence alignment of homologous subunits, which may play a role(s) in poor turnover of PA. IMPORTANCE Benzyl butyl phthalate (BBP), an estrogenic, high-molecular-weight phthalic acid diester, is an extensively used plasticizer throughout the world. Due to its structural rigidity and hydrophobic nature, BBP gets adsorbed on sediments and largely escapes the biotic and abiotic degradative processes of the ecosystem. In the present study, a potent BBP-degrading bacterial strain belonging to the genus Rhodococcus was isolated that can also assimilate a number of other phthalate diesters of environmental concern. Various biochemical and multi-omics analyses revealed that the strain harbors all the required catabolic machinery for the degradation of the plasticizer and elucidated the inducible regulation of the associated catabolic genes and gene clusters.

Project description:BackgroundDBP is one of the most commonly used plasticizers for imparting desirable properties to polymers. The introduction of phthalates is reported to have occurred in the late 1920s, and there has been a significant rise in their release into the environment in past decades due to a lack of covalent bonding with the parent matrix. Because of their numerous applications in day-to-day life, phthalates have become ubiquitous and also classified as endocrine disruptors. Hence, several studies have been conducted to investigate the phthalate-mediated toxicities in animals; however, plants have not been explored to the same amount.MethodsTherefore, in the present study, the accumulation and translocation along with morpho-physiological perturbations in barley plants after 15, 30, 60, and 120 days of exposure to di-n-butyl phthalate (DBP) are investigated using standard protocols.ResultsThe maximal accumulation and translocation of DBP in the roots and shoots of barley plants was observed after 60 days of exposure. The exposure of DBP from 15 to 120 days was recorded to decline all the morphological indices (i.e., dry weight, net primary productivity, seed number per spike, and seed weight) of barley plants. The pigments content declined under DBP treatment for all exposure durations except 120 days exposure. Carbohydrate content increased after 15-30 days of exposure afterward it was observed to be decreased under 60 and 120 days of exposure. The protein content was declined in DBP stressed plants for 15-120 days. Proline content was increased in all exposure durations and maximal percent increase was recorded in 120 days of exposure. MDA content showed an increase at earlier exposure durations then followed by a decline in long-term exposure. Hydrogen peroxide content increased at all exposure durations. There were significant alterations observed in the activities of all antioxidative enzymes in comparison to the control. Furthermore, DBP stressed plants after 60 days were analyzed for the macromolecular variations using Fourier transform infrared spectroscopy (FTIR).ConclusionThus, the outcomes of the current work provide an appraisal of phthalates' uptake and translocation mediated phytotoxic responses in barley plants. These observations can help in developing genetically modified edible plants that are resistant to phthalates uptake, thereby ensuring food security.

Dataset Information

The plasticizer butyl benzyl phthalate induces genomic changes in rat mammary gland after neonatal/prepubertal exposure.

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The plasticizer butyl benzyl phthalate induces genomic changes in rat mammary gland after neonatal/prepubertal exposure.

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