RGD Reference Report - Time-response effects of testicular gene expression profiles in Sprague-Dawley male rats treated with di(n-butyl) phthalate. - Rat Genome Database

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Time-response effects of testicular gene expression profiles in Sprague-Dawley male rats treated with di(n-butyl) phthalate.

Authors: Ryu, JY  Lee, E  Kim, TH  Lee, YJ  Lee, J  Lee, BM  Kwack, SJ  Jung, KK  Han, SY  Kim, SH  Kacew, S  Kim, HS 
Citation: Ryu JY, etal., J Toxicol Environ Health A. 2008;71(23):1542-9.
RGD ID: 2317622
Pubmed: PMID:18923996   (View Abstract at PubMed)
DOI: DOI:10.1080/15287390802391992   (Journal Full-text)

Phthalate esters were reported to damage fetal and postnatal testes of experimental animals, but the molecular mechanisms underlying these effects remain unknown. The time-response effects of di(n-butyl) phthalate (DBP) on the expression patterns of the testicular genes in male Sprague-Dawley rats were examined for different periods of exposure (1, 7, 14, or 28 d). The steroidogenic- or spermatogenic-related gene expression patterns were measured using reverse-transcription polymerase chain reaction (RT-PCR). After 28 d of exposure, the serum concentrations of DBP and monobutyl phthalate (MBP) increased in a dose-dependent manner, and were significantly higher in the DBP-treated rats than in the control rats. Liver weight was increased markedly at 28 d after DBP exposure at 750 mg/kg/d. Testicular weight was reduced significantly after 14 and 28 d of exposure. DBP (750 mg/kg/d) produced a significant increase in scavenger receptor class B1 (SR-B1) and steroidogenic acute regulatory (StAR) mRNA after 14 and 28 d of exposure. The level of cytochrome P-450 (P450) side-chain cleavage (P450scc) mRNA decreased in the group treated with DBP at 750 mg/kg/d at 7 d. After 14 and 28 d of exposure, there was an apparent increase in P450scc mRNA. High doses of DBP significantly increased the Cyp17 mRNA level after 28 d of exposure. At 7 d, a significant decrease in Cyp19 mRNA was observed only in the group exposed to 750 mg/kg/d DBP. In addition, DBP significantly decreased the levels of a spermatid-specific gene (Spag4) and lactate dehydrogenase A (LDHA) mRNA after 7 d of exposure. The levels of androgen receptor (AR), estrogen receptor-alpha (ER-alpha), and retinoid X receptor-gamma (RXR-r) expression decreased significantly in a time- or dose-dependent manner. DBP significantly increased the peroxisome proliferator-activated receptor-gamma (PPAR-r) and phosphorylated extracellular-signal-regulated kinase (p-ERK1/2) levels in the testis. These results suggest that the acute and chronic effects of DBP on the steroidogenic pathways in the testes show mechanistically distinct patterns. Data thus provide some insights into the molecular mechanisms underlying DBP-induced testicular dysgenesis.

Gene Ontology Annotations    Click to see Annotation Detail View

Biological Process
TermQualifierEvidenceWithReferenceNotesSourceOriginal Reference(s)
phthalate metabolic process  IEP 2317622din-butyl phthalateRGD 
response to organic cyclic compound  IEP 2317622din-butyl phthalateRGD 
response to organic cyclic compound  IEP 2317622 RGD 

Objects Annotated

Genes (Rattus norvegicus)
Cyp11a1  (cytochrome P450, family 11, subfamily a, polypeptide 1)
Cyp17a1  (cytochrome P450, family 17, subfamily a, polypeptide 1)
Rxrg  (retinoid X receptor gamma)

Objects referenced in this article
Gene Cyp19a1 cytochrome P450, family 19, subfamily a, polypeptide 1 Rattus norvegicus

Additional Information