Prenatal exposure to mixtures of xenoestrogens and repetitive element DNA methylation changes in human placenta

Nadia Vilahur, Mariona Bustamante, Hyang Min Byun, Mariana F. Fernandez, Loreto Santa Marina, Mikel Basterrechea, Ferran Ballester, Mario Murcia, Adonina Tardón, Ana Fernández-Somoano, Xavier P. Estivill, Nicolas Olea, Jordi Sunyer, Andrea A. Baccarelli

Research output: Contribution to journalArticle

24 Citations (Scopus)

Abstract

Background: Prenatal exposure to endocrine disrupting compounds (EDCs) has previously shown to alter epigenetic marks. Objectives: In this work we explore whether prenatal exposure to mixtures of xenoestrogens has the potential to alter the placenta epigenome, by studying DNA methylation in retrotransposons as a surrogate of global DNA methylation. Methods: The biomarker total effective xenoestrogen burden (TEXB) was measured in 192 placentas from participants in the longitudinal INMA Project. DNA methylation was quantitatively assessed by bisulfite pyrosequencing on 10 different retrotransposons including 3 different long interspersed nuclear elements (LINEs), 4 short interspersed nuclear elements (SINEs) and 3 human endogenous retroviruses (HERVs). Associations were tested using linear mixed-effects regression models and sex interaction was evaluated. Results: A significant sex interaction was observed for AluYb8 (p-value for interaction <. 0.001, significant at Bonferroni corrected p-value threshold of 0.0025). Boys with the highest TEXB-alpha levels of exposure (third tertile) presented on average a decrease of 0.84% in methylation compared to those in the first tertile (p-value. <. 0.001), while no significant effects were found in girls (p-value=0.134). Conclusions: Our findings suggest that boys may be more susceptible to the effect of exposure to xenoestrogens during prenatal development, producing shifts in DNA methylation of certain sensitive genomic repetitive sequences in a tissue important for fetal growth and development.

Original languageEnglish
Pages (from-to)81-87
Number of pages7
JournalEnvironment International
Volume71
DOIs
Publication statusPublished - 2014
Externally publishedYes

Fingerprint

methylation
DNA
growth and development
biomarker
genomics
exposure
effect

Keywords

  • Biomarker
  • Global DNA methylation
  • Placenta
  • Sex
  • TEXB
  • Xenoestrogens

ASJC Scopus subject areas

  • Environmental Science(all)

Cite this

Vilahur, N., Bustamante, M., Byun, H. M., Fernandez, M. F., Santa Marina, L., Basterrechea, M., ... Baccarelli, A. A. (2014). Prenatal exposure to mixtures of xenoestrogens and repetitive element DNA methylation changes in human placenta. Environment International, 71, 81-87. https://doi.org/10.1016/j.envint.2014.06.006

Prenatal exposure to mixtures of xenoestrogens and repetitive element DNA methylation changes in human placenta. / Vilahur, Nadia; Bustamante, Mariona; Byun, Hyang Min; Fernandez, Mariana F.; Santa Marina, Loreto; Basterrechea, Mikel; Ballester, Ferran; Murcia, Mario; Tardón, Adonina; Fernández-Somoano, Ana; Estivill, Xavier P.; Olea, Nicolas; Sunyer, Jordi; Baccarelli, Andrea A.

In: Environment International, Vol. 71, 2014, p. 81-87.

Research output: Contribution to journalArticle

Vilahur, N, Bustamante, M, Byun, HM, Fernandez, MF, Santa Marina, L, Basterrechea, M, Ballester, F, Murcia, M, Tardón, A, Fernández-Somoano, A, Estivill, XP, Olea, N, Sunyer, J & Baccarelli, AA 2014, 'Prenatal exposure to mixtures of xenoestrogens and repetitive element DNA methylation changes in human placenta', Environment International, vol. 71, pp. 81-87. https://doi.org/10.1016/j.envint.2014.06.006
Vilahur, Nadia ; Bustamante, Mariona ; Byun, Hyang Min ; Fernandez, Mariana F. ; Santa Marina, Loreto ; Basterrechea, Mikel ; Ballester, Ferran ; Murcia, Mario ; Tardón, Adonina ; Fernández-Somoano, Ana ; Estivill, Xavier P. ; Olea, Nicolas ; Sunyer, Jordi ; Baccarelli, Andrea A. / Prenatal exposure to mixtures of xenoestrogens and repetitive element DNA methylation changes in human placenta. In: Environment International. 2014 ; Vol. 71. pp. 81-87.
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abstract = "Background: Prenatal exposure to endocrine disrupting compounds (EDCs) has previously shown to alter epigenetic marks. Objectives: In this work we explore whether prenatal exposure to mixtures of xenoestrogens has the potential to alter the placenta epigenome, by studying DNA methylation in retrotransposons as a surrogate of global DNA methylation. Methods: The biomarker total effective xenoestrogen burden (TEXB) was measured in 192 placentas from participants in the longitudinal INMA Project. DNA methylation was quantitatively assessed by bisulfite pyrosequencing on 10 different retrotransposons including 3 different long interspersed nuclear elements (LINEs), 4 short interspersed nuclear elements (SINEs) and 3 human endogenous retroviruses (HERVs). Associations were tested using linear mixed-effects regression models and sex interaction was evaluated. Results: A significant sex interaction was observed for AluYb8 (p-value for interaction <. 0.001, significant at Bonferroni corrected p-value threshold of 0.0025). Boys with the highest TEXB-alpha levels of exposure (third tertile) presented on average a decrease of 0.84{\%} in methylation compared to those in the first tertile (p-value. <. 0.001), while no significant effects were found in girls (p-value=0.134). Conclusions: Our findings suggest that boys may be more susceptible to the effect of exposure to xenoestrogens during prenatal development, producing shifts in DNA methylation of certain sensitive genomic repetitive sequences in a tissue important for fetal growth and development.",
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AU - Bustamante, Mariona

AU - Byun, Hyang Min

AU - Fernandez, Mariana F.

AU - Santa Marina, Loreto

AU - Basterrechea, Mikel

AU - Ballester, Ferran

AU - Murcia, Mario

AU - Tardón, Adonina

AU - Fernández-Somoano, Ana

AU - Estivill, Xavier P.

AU - Olea, Nicolas

AU - Sunyer, Jordi

AU - Baccarelli, Andrea A.

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N2 - Background: Prenatal exposure to endocrine disrupting compounds (EDCs) has previously shown to alter epigenetic marks. Objectives: In this work we explore whether prenatal exposure to mixtures of xenoestrogens has the potential to alter the placenta epigenome, by studying DNA methylation in retrotransposons as a surrogate of global DNA methylation. Methods: The biomarker total effective xenoestrogen burden (TEXB) was measured in 192 placentas from participants in the longitudinal INMA Project. DNA methylation was quantitatively assessed by bisulfite pyrosequencing on 10 different retrotransposons including 3 different long interspersed nuclear elements (LINEs), 4 short interspersed nuclear elements (SINEs) and 3 human endogenous retroviruses (HERVs). Associations were tested using linear mixed-effects regression models and sex interaction was evaluated. Results: A significant sex interaction was observed for AluYb8 (p-value for interaction <. 0.001, significant at Bonferroni corrected p-value threshold of 0.0025). Boys with the highest TEXB-alpha levels of exposure (third tertile) presented on average a decrease of 0.84% in methylation compared to those in the first tertile (p-value. <. 0.001), while no significant effects were found in girls (p-value=0.134). Conclusions: Our findings suggest that boys may be more susceptible to the effect of exposure to xenoestrogens during prenatal development, producing shifts in DNA methylation of certain sensitive genomic repetitive sequences in a tissue important for fetal growth and development.

AB - Background: Prenatal exposure to endocrine disrupting compounds (EDCs) has previously shown to alter epigenetic marks. Objectives: In this work we explore whether prenatal exposure to mixtures of xenoestrogens has the potential to alter the placenta epigenome, by studying DNA methylation in retrotransposons as a surrogate of global DNA methylation. Methods: The biomarker total effective xenoestrogen burden (TEXB) was measured in 192 placentas from participants in the longitudinal INMA Project. DNA methylation was quantitatively assessed by bisulfite pyrosequencing on 10 different retrotransposons including 3 different long interspersed nuclear elements (LINEs), 4 short interspersed nuclear elements (SINEs) and 3 human endogenous retroviruses (HERVs). Associations were tested using linear mixed-effects regression models and sex interaction was evaluated. Results: A significant sex interaction was observed for AluYb8 (p-value for interaction <. 0.001, significant at Bonferroni corrected p-value threshold of 0.0025). Boys with the highest TEXB-alpha levels of exposure (third tertile) presented on average a decrease of 0.84% in methylation compared to those in the first tertile (p-value. <. 0.001), while no significant effects were found in girls (p-value=0.134). Conclusions: Our findings suggest that boys may be more susceptible to the effect of exposure to xenoestrogens during prenatal development, producing shifts in DNA methylation of certain sensitive genomic repetitive sequences in a tissue important for fetal growth and development.

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