PMID- 23285176
OWN - NLM
STAT- MEDLINE
DCOM- 20130627
LR  - 20211021
IS  - 1932-6203 (Electronic)
IS  - 1932-6203 (Linking)
VI  - 7
IP  - 12
DP  - 2012
TI  - Individual variation of the genetic response to bisphenol a in human foreskin 
      fibroblast cells derived from cryptorchidism and hypospadias patients.
PG  - e52756
LID - 10.1371/journal.pone.0052756 [doi]
LID - e52756
AB  - BACKGROUND/PURPOSE: We hypothesized that polymorphic differences among 
      individuals might cause variations in the effect that environmental endocrine 
      disruptors (EEDs) have on male genital malformations (MGMs). In this study, 
      individual variation in the genetic response to low-dose bisphenol A (BPA) was 
      investigated in human foreskin fibroblast cells (hFFCs) derived from child 
      cryptorchidism (CO) and hypospadias (HS) patients. METHODOLOGY/PRINCIPAL 
      FINDINGS: hFFCs were collected from control children without MGMs (n=5) and child 
      CO and HS patients (n=8 and 21, respectively). BPA exposure (10 nM) was found to 
      inhibit matrix metalloproteinase-11 (MMP11) expression in the HS group 
      (0.74-fold, P=0.0034) but not in the control group (0.93-fold, P=0.84) and CO 
      group (0.94-fold, P=0.70). Significantly lower levels of MMP11 expression were 
      observed in the HS group compared with the control group (0.80-fold, P=0.0088) 
      and CO group (0.79-fold, P=0.039) in response to 10 nM BPA. The effect of 
      single-nucleotide polymorphism rs5000770 (G>A), located within the aryl 
      hydrocarbon receptor nuclear translocator 2 (ARNT2) locus, on individual 
      sensitivity to low-dose BPA was investigated in the HS group. A significant 
      difference in neurotensin receptor 1 (NTSR1) expression in response to 10 nM BPA 
      was observed between AA and AG/GG groups (n=6 and 15, respectively. P=0.031). 
      However, no significant difference in ARNT2 expression was observed (P=0.18). 
      CONCLUSIONS/SIGNIFICANCE: This study advances our understanding of the 
      specificity of low-dose BPA effects on human reproductive health. Our results 
      suggest that genetic variability among individuals affects susceptibility to the 
      effects of EEDs exposure as a potential cause of HS.
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 - Sone, Hideko
AU  - Sone H
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 - Hisada, Aya
AU  - Hisada A
FAU - Zaha, Hiroko
AU  - Zaha H
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
LA  - eng
PT  - Journal Article
PT  - Research Support, Non-U.S. Gov't
DEP - 20121228
PL  - United States
TA  - PLoS One
JT  - PloS one
JID - 101285081
RN  - 0 (ARNT2 protein, human)
RN  - 0 (Basic Helix-Loop-Helix Transcription Factors)
RN  - 0 (Benzhydryl Compounds)
RN  - 0 (Endocrine Disruptors)
RN  - 0 (Phenols)
RN  - 0 (RNA, Messenger)
RN  - 138391-32-9 (Aryl Hydrocarbon Receptor Nuclear Translocator)
RN  - MLT3645I99 (bisphenol A)
SB  - IM
MH  - Alternative Splicing
MH  - Aryl Hydrocarbon Receptor Nuclear Translocator/genetics
MH  - Basic Helix-Loop-Helix Transcription Factors/genetics
MH  - Benzhydryl Compounds/administration & dosage/*adverse effects
MH  - Cells, Cultured
MH  - Cryptorchidism/etiology/*genetics
MH  - Endocrine Disruptors/administration & dosage/*adverse effects
MH  - Environmental Exposure/adverse effects
MH  - Fibroblasts/*drug effects/*metabolism
MH  - Foreskin/*cytology
MH  - Gene Order
MH  - Genotype
MH  - Humans
MH  - Hypospadias/etiology/*genetics
MH  - Male
MH  - Phenols/administration & dosage/*adverse effects
MH  - RNA, Messenger/genetics/metabolism
PMC - PMC3532342
COIS- Competing Interests: The authors have declared that no competing interests exist.
EDAT- 2013/01/04 06:00
MHDA- 2013/06/29 06:00
PMCR- 2012/12/28
CRDT- 2013/01/04 06:00
PHST- 2012/07/03 00:00 [received]
PHST- 2012/11/20 00:00 [accepted]
PHST- 2013/01/04 06:00 [entrez]
PHST- 2013/01/04 06:00 [pubmed]
PHST- 2013/06/29 06:00 [medline]
PHST- 2012/12/28 00:00 [pmc-release]
AID - PONE-D-12-20684 [pii]
AID - 10.1371/journal.pone.0052756 [doi]
PST - ppublish
SO  - PLoS One. 2012;7(12):e52756. doi: 10.1371/journal.pone.0052756. Epub 2012 Dec 28.