Individual Variation of the Genetic Response to Bisphenol A in Human Foreskin Fibroblast Cells Derived from Cryptorchidism and Hypospadias Patients

Autor: Tomokazu Fukuda, Tsutomu Ogata, Jun Yoshinaga, Mami Miyado, Koji Muroya, Hideko Sone, Katsuhiko Ueoka, Yoshiyuki Kojima, Yutaro Hayashi, Hiroko Zaha, Junzo Yonemoto, Maki Fukami, Kentaro Mizuno, Kenjiro Kohri, Aya Hisada, Xian-Yang Qin
Jazyk: angličtina
Rok vydání: 2012
Předmět:
Male
Anatomy and Physiology
Endocrine Disruptors
Toxicology
Pediatrics
Foreskin
Reproductive Physiology
Genotype
Cryptorchidism
Gene Order
Basic Helix-Loop-Helix Transcription Factors
Cells
Cultured
Hypospadias
Multidisciplinary
Pediatric Urology
Environmental exposure
medicine.anatomical_structure
Medicine
Genital Anatomy
hormones
hormone substitutes
and hormone antagonists
Research Article
endocrine system
medicine.medical_specialty
Sexual Dysfunction
Genetic Toxicology
Science
Urology
Toxic Agents
Biology
Phenols
Molecular genetics
Internal medicine
medicine
Endocrine system
Humans
Sex organ
RNA
Messenger
Benzhydryl Compounds
Fibroblast
urogenital system
Aryl Hydrocarbon Receptor Nuclear Translocator
Reproductive System
Environmental Exposure
Fibroblasts
medicine.disease
Alternative Splicing
Endocrinology
Zdroj: PLoS ONE
PLoS ONE, Vol 7, Iss 12, p e52756 (2012)
ISSN: 1932-6203
Popis: Background/purposeWe 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 findingshFFCs 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/significanceThis 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.
Databáze: OpenAIRE
Externí odkaz: