Individual variation of the genetic response to bisphenol a in human foreskin fibroblast cells derived from cryptorchidism and hypospadias patients.
<h4>Background/purpose</h4>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...
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oai:doaj.org-article:67d83a867c9b4833801bf87e09b8a9da2021-11-18T08:03:18ZIndividual variation of the genetic response to bisphenol a in human foreskin fibroblast cells derived from cryptorchidism and hypospadias patients.1932-620310.1371/journal.pone.0052756https://doaj.org/article/67d83a867c9b4833801bf87e09b8a9da2012-01-01T00:00:00Zhttps://www.ncbi.nlm.nih.gov/pmc/articles/pmid/23285176/?tool=EBIhttps://doaj.org/toc/1932-6203<h4>Background/purpose</h4>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.<h4>Methodology/principal findings</h4>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).<h4>Conclusions/significance</h4>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.Xian-Yang QinHideko SoneYoshiyuki KojimaKentaro MizunoKatsuhiko UeokaKoji MuroyaMami MiyadoAya HisadaHiroko ZahaTomokazu FukudaJun YoshinagaJunzo YonemotoKenjiro KohriYutaro HayashiMaki FukamiTsutomu OgataPublic Library of Science (PLoS)articleMedicineRScienceQENPLoS ONE, Vol 7, Iss 12, p e52756 (2012) |
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Medicine R Science Q Xian-Yang Qin Hideko Sone Yoshiyuki Kojima Kentaro Mizuno Katsuhiko Ueoka Koji Muroya Mami Miyado Aya Hisada Hiroko Zaha Tomokazu Fukuda Jun Yoshinaga Junzo Yonemoto Kenjiro Kohri Yutaro Hayashi Maki Fukami Tsutomu Ogata Individual variation of the genetic response to bisphenol a in human foreskin fibroblast cells derived from cryptorchidism and hypospadias patients. |
| description |
<h4>Background/purpose</h4>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.<h4>Methodology/principal findings</h4>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).<h4>Conclusions/significance</h4>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. |
| format |
article |
| author |
Xian-Yang Qin Hideko Sone Yoshiyuki Kojima Kentaro Mizuno Katsuhiko Ueoka Koji Muroya Mami Miyado Aya Hisada Hiroko Zaha Tomokazu Fukuda Jun Yoshinaga Junzo Yonemoto Kenjiro Kohri Yutaro Hayashi Maki Fukami Tsutomu Ogata |
| author_facet |
Xian-Yang Qin Hideko Sone Yoshiyuki Kojima Kentaro Mizuno Katsuhiko Ueoka Koji Muroya Mami Miyado Aya Hisada Hiroko Zaha Tomokazu Fukuda Jun Yoshinaga Junzo Yonemoto Kenjiro Kohri Yutaro Hayashi Maki Fukami Tsutomu Ogata |
| author_sort |
Xian-Yang Qin |
| title |
Individual variation of the genetic response to bisphenol a in human foreskin fibroblast cells derived from cryptorchidism and hypospadias patients. |
| title_short |
Individual variation of the genetic response to bisphenol a in human foreskin fibroblast cells derived from cryptorchidism and hypospadias patients. |
| title_full |
Individual variation of the genetic response to bisphenol a in human foreskin fibroblast cells derived from cryptorchidism and hypospadias patients. |
| title_fullStr |
Individual variation of the genetic response to bisphenol a in human foreskin fibroblast cells derived from cryptorchidism and hypospadias patients. |
| title_full_unstemmed |
Individual variation of the genetic response to bisphenol a in human foreskin fibroblast cells derived from cryptorchidism and hypospadias patients. |
| title_sort |
individual variation of the genetic response to bisphenol a in human foreskin fibroblast cells derived from cryptorchidism and hypospadias patients. |
| publisher |
Public Library of Science (PLoS) |
| publishDate |
2012 |
| url |
https://doaj.org/article/67d83a867c9b4833801bf87e09b8a9da |
| work_keys_str_mv |
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