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

Moral R, Wang R, Russo IH, Mailo DA, Lamartiniere CA, Russo J - BMC Genomics (2007)

Bottom Line: BBP has shown endocrine-disrupting properties, thus having a potential effect on hormone-sensitive tissues.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.These results suggest that BBP has an effect in the gene expression profile of the mammary gland.

View Article: PubMed Central - HTML - PubMed

Affiliation: Breast Cancer Research Laboratory, Fox Chase Cancer Center, Philadelphia, PA 19111, USA. Raquel.Moral@uab.es

ABSTRACT

Background: 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).

Results: 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.

Conclusion: These results suggest that BBP has an effect in the gene expression profile of the mammary gland.

Show MeSH

Related in: MedlinePlus

Comparative expression analyses of selected genes. Gene expression analyses by real time RT-PCR in comparison with results from microarrays. Grey bars represent results obtained in the microarrays, black bars represent results obtained in the real time RT-PCR. Results show the mean fold expression of the treated group related to control group. The functional categories significantly over-represented are indicated (21 days). *: significant differences compared to control group (p < 0.05).
© Copyright Policy - open-access
Related In: Results  -  Collection

License
getmorefigures.php?uid=PMC2200869&req=5

Figure 3: Comparative expression analyses of selected genes. Gene expression analyses by real time RT-PCR in comparison with results from microarrays. Grey bars represent results obtained in the microarrays, black bars represent results obtained in the real time RT-PCR. Results show the mean fold expression of the treated group related to control group. The functional categories significantly over-represented are indicated (21 days). *: significant differences compared to control group (p < 0.05).

Mentions: To validate the results from microarrays we have chosen several genes that were differentially expressed in the mammary glands from BBP treated rats: transcription factors related to proliferation and differentiation (Foxg1, Hfh1, Nfyc, Ahr, Wt1, Tsn), other genes related to differentiation (Fabp3), adhesion (Cdh8) and communication (Gad1). We analyzed the gene expression of those genes by real time RT-PCR. Results of the validation are shown in Figure 3. In the BBP exposed animals Foxg1, Hfh1, Nfyc and Ahr were between 1.6- and 2-fold up-regulated in comparison to their gene expression in untreated animals. These differences, although discrete, were statistically significant for Hfh1 and Ahr, and close to significance for the other genes. We also obtained statistically significant increases in the expression of Fabp3, Wt1 and Cadh8. By 35 and 50 days, BBP exposure induced a significant decrease in the expression of Gad1. The decrease of this gene found by microarrays at 21 days as well as the increase in Tsn observed by 100 days of age was not confirmed by real time PCR.


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

Moral R, Wang R, Russo IH, Mailo DA, Lamartiniere CA, Russo J - BMC Genomics (2007)

Comparative expression analyses of selected genes. Gene expression analyses by real time RT-PCR in comparison with results from microarrays. Grey bars represent results obtained in the microarrays, black bars represent results obtained in the real time RT-PCR. Results show the mean fold expression of the treated group related to control group. The functional categories significantly over-represented are indicated (21 days). *: significant differences compared to control group (p < 0.05).
© Copyright Policy - open-access
Related In: Results  -  Collection

License
Show All Figures
getmorefigures.php?uid=PMC2200869&req=5

Figure 3: Comparative expression analyses of selected genes. Gene expression analyses by real time RT-PCR in comparison with results from microarrays. Grey bars represent results obtained in the microarrays, black bars represent results obtained in the real time RT-PCR. Results show the mean fold expression of the treated group related to control group. The functional categories significantly over-represented are indicated (21 days). *: significant differences compared to control group (p < 0.05).
Mentions: To validate the results from microarrays we have chosen several genes that were differentially expressed in the mammary glands from BBP treated rats: transcription factors related to proliferation and differentiation (Foxg1, Hfh1, Nfyc, Ahr, Wt1, Tsn), other genes related to differentiation (Fabp3), adhesion (Cdh8) and communication (Gad1). We analyzed the gene expression of those genes by real time RT-PCR. Results of the validation are shown in Figure 3. In the BBP exposed animals Foxg1, Hfh1, Nfyc and Ahr were between 1.6- and 2-fold up-regulated in comparison to their gene expression in untreated animals. These differences, although discrete, were statistically significant for Hfh1 and Ahr, and close to significance for the other genes. We also obtained statistically significant increases in the expression of Fabp3, Wt1 and Cadh8. By 35 and 50 days, BBP exposure induced a significant decrease in the expression of Gad1. The decrease of this gene found by microarrays at 21 days as well as the increase in Tsn observed by 100 days of age was not confirmed by real time PCR.

Bottom Line: BBP has shown endocrine-disrupting properties, thus having a potential effect on hormone-sensitive tissues.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.These results suggest that BBP has an effect in the gene expression profile of the mammary gland.

View Article: PubMed Central - HTML - PubMed

Affiliation: Breast Cancer Research Laboratory, Fox Chase Cancer Center, Philadelphia, PA 19111, USA. Raquel.Moral@uab.es

ABSTRACT

Background: 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).

Results: 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.

Conclusion: These results suggest that BBP has an effect in the gene expression profile of the mammary gland.

Show MeSH
Related in: MedlinePlus