Related Experiment Video

Updated: May 14, 2026

Detection of Signaling Effector-Complexes Downstream of BMP4 Using in situ PLA, a Proximity Ligation Assay
12:52

Detection of Signaling Effector-Complexes Downstream of BMP4 Using in situ PLA, a Proximity Ligation Assay

Published on: March 3, 2011

Identification of transcription factors and coactivators affected by dibutylphthalate interactions in fetal rat

Simon M Plummer1, Dhritiman Dan, Joanne Quinney

  • 1CXR Biosciences Ltd, Dundee DD1 5JJ, UK. simonplummer@micromatrices.com

Toxicological Sciences : an Official Journal of the Society of Toxicology
|January 30, 2013
PubMed

Insights

Dibutylphthalate (DBP) exposure in fetal rats disrupts steroidogenesis by inhibiting steroidogenic factor 1 (SF1) binding and increasing peroxisome proliferator-activated receptor alpha (PPARα) binding to key genes. This suggests PPARα acts as a transrepressor, contributing to testicular maldevelopment.

Area of Science:

  • Endocrinology
  • Toxicology
  • Molecular Biology

Background:

  • In utero exposure to dibutylphthalate (DBP) causes antiandrogenic effects in fetal rat testes.
  • Previous studies suggest DBP's effects involve indirect inhibition of steroidogenic factor 1 (SF1).
  • Peroxisome proliferator-activated receptor alpha (PPARα) involvement via coactivator sequestration was hypothesized.

Purpose of the Study:

  • To investigate the role of PPARα in DBP-induced testicular maldevelopment.
  • To assess the DNA binding of PPARα, SF1, CBP, and RNA polymerase II in DBP-exposed fetal rat testes.
  • To determine if DBP alters SF1 and PPARα binding to steroidogenic genes.

Main Methods:

  • Chromatin immunoprecipitation (ChIP) microarray analysis was performed on fetal rat testes.
  • Gene expression data from gestational days 15, 17, and 19 were analyzed.
  • Specific gene targets including CYP11a, StAR, CYP17a, and FSHR were examined for protein binding.

Main Results:

  • DBP treatment reduced SF1 binding to CYP11a, StAR, and CYP17a genes.
  • DBP treatment increased PPARα binding to regulatory regions of CYP11a, StAR, and CYP17a.
  • PPARα binding was not detected in the FSHR promoter, which was unaffected by DBP.

Conclusions:

  • DBP-induced repression of SF1-regulated steroidogenic genes correlates with reduced SF1 DNA binding and increased PPARα DNA binding.
  • PPARα may function as an indirect transrepressor of SF1 on steroidogenic genes in response to DBP.
  • These findings elucidate a mechanism for DBP's antiandrogenic effects during testicular development.

More Related Videos

Long-term Behavioral and Reproductive Consequences of Embryonic Exposure to Low-dose Toxicants07:08

Long-term Behavioral and Reproductive Consequences of Embryonic Exposure to Low-dose Toxicants

Published on: March 6, 2018

Developmental Toxicity Assay Based on Real-Time Monitoring of Fibroblast Growth Factor Signal Disruption in Human Induced Pluripotent Stem Cells05:45

Developmental Toxicity Assay Based on Real-Time Monitoring of Fibroblast Growth Factor Signal Disruption in Human Induced Pluripotent Stem Cells

Published on: October 10, 2025

Related Concept Videos

Master Transcription Regulators02:23

Master Transcription Regulators

Master transcription regulators are regulatory proteins that are predominantly responsible for regulating the expression of multiple genes. Often these genes work in concert to drive a  complex process. Activation of a master transcription regulator can lead to a cascade of transcriptional activation necessary for that outcome. These regulators can directly bind to the regulatory sequences of the various genes involved, or they can indirectly regulate transcription by binding to regulatory...
General Transcription Factors01:30

General Transcription Factors

Tissue-specific transcription factors contribute to diverse cellular functions in mammals. For example, the gene for beta globin, a major component of hemoglobin, is present in all cells of the body. However, it is only expressed in red blood cells because the transcription factors that can bind to the promoter sequences of the beta globin gene are only expressed in these cells. Tissue-specific transcription factors also ensure that mutations in these factors may impair only the function of...