Prenatal Exposure to Mixtures of Xenoestrogens and Genome-Wide DNA Methylation in Human Placenta

Abstract

Background: In utero exposure to xenostrogens may modify the epigenome. We explored the association of prenatal exposure to mixtures of xenoestrogens and genome-wide placental DNA methylation. Materials & methods: Sex-specific associations between methylation changes in placental DNA by doubling the concentration of TEXB-alpha exposure were evaluated by robust multiple linear regression. Two CpG sites were selected for validation and replication in additional male born placentas. Results: No significant associations were found, although the top significant CpGs in boys were located in the LRPAP1, HAGH, PPARGC1B, KCNQ1 and KCNQ1DN genes, previously associated to birth weight, Type 2 diabetes, obesity or steroid hormone signaling. Neither technical validation nor biological replication of the results was found in boys for LRPAP and PPARGC1B. Conclusion: Some suggestive genes were differentially methylated in boys in relation to prenatal xenoestrogen exposure, but our initial findings could not be validated or replicated.

Keywords::

• DNA methylation
• endocrine disruptors
• epigenome xenoestrogens
• placenta
• prenatal
• programming
• TEXB

To view the supplementary data that accompany this paper please visitthe journal website at: www.tandfonline.com/doi/full/10.2217/epi.15.91

Acknowledgements

The authors acknowledge all the study participants for their generous collaboration. A full list of INMA Study Investigators can be found at: www.proyectoinma.org/presentacion-inma/listado-investigadores/listado-investigadores.html

Financial & competing interests disclosure

This work was supported by grants from the Spanish Ministry of Health (FIS-PI042018; FIS-PI060867; FIS-PI081151; FIS-PI09/02311; FIS-PI09/02647; FIS-PI11/00610; FIS-PI13/02429); Instituto de Salud Carlos III (Red INMA G03/176 and CB06/02/0041); the EU Commission (QLK4-1999-01422, QLK4-2002-00603 and CONTAMED FP7-ENV-212502), the Generalitat de Catalunya-CIRIT (1999SGR 00241); the Fundació La Marató de TV3; the Consejería de Salud de la Junta de Andalucía (grant number 183/07 and 0675/10), the Diputación Foral de Gipuzkoa (DFG06/004), the Department of Health of the Basque Government (2005111093), the University of Oviedo, the Fundación Liberbank, and the Fundación Roger Torné.

Nadia Vilahur was supported by an FPI Grant from the Spanish Ministry of Health (BES-2009-023933) and a Formación de Personal Investigador Grant for Short Research Stays in Foreign Institutions (BES-2009-023933). The HUSC BioBank, integrated in the Andalusia Public Health System (SSPA) and the National Biobank Network, is financed by the Institute of Health Carlos III, (project RD09/0076/00148) and the Regional Government of Andalusia.

The authors have no other relevant affiliations or financial involvement with any organization or entity with a financial interest in or financial conflict with the subject matter or materials discussed in the manuscript apart from those disclosed.

No writing assistance was utilized in the production of this manuscript.

Ethical conduct of research

The authors state that they have obtained appropriate institutional review board approval or have followed the principles outlined in the Declaration of Helsinki for all human or animal experimental investigations. In addition, for investigations involving human subjects, informed consent has been obtained from the participants involved and/or their legal tutors.

Additional information

Funding

This work was supported by grants from the Spanish Ministry of Health (FIS-PI042018; FIS-PI060867; FIS-PI081151; FIS-PI09/02311; FIS-PI09/02647; FIS-PI11/00610; FIS-PI13/02429); Instituto de Salud Carlos III (Red INMA G03/176 and CB06/02/0041); the EU Commission (QLK4-1999-01422, QLK4-2002-00603 and CONTAMED FP7-ENV-212502), the Generalitat de Catalunya-CIRIT (1999SGR 00241); the Fundació La Marató de TV3; the Consejería de Salud de la Junta de Andalucía (grant number 183/07 and 0675/10), the Diputación Foral de Gipuzkoa (DFG06/004), the Department of Health of the Basque Government (2005111093), the University of Oviedo, the Fundación Liberbank, and the Fundación Roger Torné. Nadia Vilahur was supported by an FPI Grant from the Spanish Ministry of Health (BES-2009-023933) and a Formación de Personal Investigador Grant for Short Research Stays in Foreign Institutions (BES-2009-023933). The HUSC BioBank, integrated in the Andalusia Public Health System (SSPA) and the National Biobank Network, is financed by the Institute of Health Carlos III, (project RD09/0076/00148) and the Regional Government of Andalusia. The authors have no other relevant affiliations or financial involvement with any organization or entity with a financial interest in or financial conflict with the subject matter or materials discussed in the manuscript apart from those disclosed. No writing assistance was utilized in the production of this manuscript.