PMID- 22574217
OWN - NLM
STAT- MEDLINE
DCOM- 20120910
LR  - 20211021
IS  - 1932-6203 (Electronic)
IS  - 1932-6203 (Linking)
VI  - 7
IP  - 5
DP  - 2012
TI  - Identification of novel low-dose bisphenol a targets in human foreskin fibroblast 
      cells derived from hypospadias patients.
PG  - e36711
LID - 10.1371/journal.pone.0036711 [doi]
LID - e36711
AB  - BACKGROUND/PURPOSE: The effect of low-dose bisphenol A (BPA) exposure on human 
      reproductive health is still controversial. To better understand the molecular 
      basis of the effect of BPA on human reproductive health, a genome-wide screen was 
      performed using human foreskin fibroblast cells (hFFCs) derived from child 
      hypospadias (HS) patients to identify novel targets of low-dose BPA exposure. 
      METHODOLOGY/PRINCIPAL FINDINGS: Gene expression profiles of hFFCs were measured 
      after exposure to 10 nM BPA, 0.01 nM 17beta-estradiol (E2) or 1 nM 
      2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD) for 24 h. Differentially expressed 
      genes were identified using an unpaired Student's t test with P value cut off at 
      0.05 and fold change of more than 1.2. These genes were selected for network 
      generation and pathway analysis using Ingenuity Pathways Analysis, Pathway 
      Express and KegArray. Seventy-one genes (42 downregulated and 29 upregulated) 
      were identified as significantly differentially expressed in response to BPA, 
      among which 43 genes were found to be affected exclusively by BPA compared with 
      E2 and TCDD. Of particular interest, real-time PCR analysis revealed that the 
      expression of matrix metallopeptidase 11 (MMP11), a well-known effector of 
      development and normal physiology, was found to be inhibited by BPA (0.47-fold 
      and 0.37-fold at 10 nM and 100 nM, respectively). Furthermore, study of hFFCs 
      derived from HS and cryptorchidism (CO) patients (n = 23 and 11, respectively) 
      indicated that MMP11 expression was significantly lower in the HS group than in 
      the CO group (0.25-fold, P = 0.0027). CONCLUSIONS/SIGNIFICANCE: This present 
      study suggests that an involvement of BPA in the etiology of HS might be 
      associated with the downregulation of MMP11. Further study to elucidate the 
      function of the novel target genes identified in this study during genital 
      tubercle development might increase our knowledge of the effects of low-dose BPA 
      exposure on human reproductive health.
FAU - Qin, Xian-Yang
AU  - Qin XY
AD  - Health Risk Research Section, Research Center for Environmental Risk, National 
      Institute for Environmental Studies, Tsukuba, Ibaraki, Japan.
FAU - Kojima, Yoshiyuki
AU  - Kojima Y
FAU - Mizuno, Kentaro
AU  - Mizuno K
FAU - Ueoka, Katsuhiko
AU  - Ueoka K
FAU - Muroya, Koji
AU  - Muroya K
FAU - Miyado, Mami
AU  - Miyado M
FAU - Zaha, Hiroko
AU  - Zaha H
FAU - Akanuma, Hiromi
AU  - Akanuma H
FAU - Zeng, Qin
AU  - Zeng Q
FAU - Fukuda, Tomokazu
AU  - Fukuda T
FAU - Yoshinaga, Jun
AU  - Yoshinaga J
FAU - Yonemoto, Junzo
AU  - Yonemoto J
FAU - Kohri, Kenjiro
AU  - Kohri K
FAU - Hayashi, Yutaro
AU  - Hayashi Y
FAU - Fukami, Maki
AU  - Fukami M
FAU - Ogata, Tsutomu
AU  - Ogata T
FAU - Sone, Hideko
AU  - Sone H
LA  - eng
PT  - Journal Article
PT  - Research Support, Non-U.S. Gov't
DEP - 20120504
PL  - United States
TA  - PLoS One
JT  - PloS one
JID - 101285081
RN  - 0 (Benzhydryl Compounds)
RN  - 0 (Environmental Pollutants)
RN  - 0 (Phenols)
RN  - 0 (Polychlorinated Dibenzodioxins)
RN  - 0 (Receptors, Aryl Hydrocarbon)
RN  - 0 (Receptors, Estrogen)
RN  - 4TI98Z838E (Estradiol)
RN  - EC 3.4.24.- (Matrix Metalloproteinase 11)
RN  - MLT3645I99 (bisphenol A)
SB  - IM
MH  - Benzhydryl Compounds
MH  - Child, Preschool
MH  - Dose-Response Relationship, Drug
MH  - Environmental Pollutants/*pharmacology
MH  - Estradiol/pharmacology
MH  - Fibroblasts/*drug effects/*metabolism/pathology
MH  - Foreskin/*pathology
MH  - Genomics
MH  - Humans
MH  - Hypospadias/*pathology
MH  - Male
MH  - Matrix Metalloproteinase 11/genetics
MH  - Phenols/*pharmacology
MH  - Polychlorinated Dibenzodioxins/pharmacology
MH  - Receptors, Aryl Hydrocarbon/metabolism
MH  - Receptors, Estrogen/metabolism
MH  - Reproducibility of Results
MH  - Reproduction/drug effects
MH  - Signal Transduction/drug effects
MH  - Transcriptome/drug effects
PMC - PMC3344929
COIS- Competing Interests: The authors have declared that no competing interests exist.
EDAT- 2012/05/11 06:00
MHDA- 2012/09/11 06:00
PMCR- 2012/05/04
CRDT- 2012/05/11 06:00
PHST- 2012/03/06 00:00 [received]
PHST- 2012/04/12 00:00 [accepted]
PHST- 2012/05/11 06:00 [entrez]
PHST- 2012/05/11 06:00 [pubmed]
PHST- 2012/09/11 06:00 [medline]
PHST- 2012/05/04 00:00 [pmc-release]
AID - PONE-D-12-06650 [pii]
AID - 10.1371/journal.pone.0036711 [doi]
PST - ppublish
SO  - PLoS One. 2012;7(5):e36711. doi: 10.1371/journal.pone.0036711. Epub 2012 May 4.