Residential green space in association with the methylation status in a CpG site within the promoter region of the placental serotonin receptor HTR2A

ABSTRACT

Green space could influence adult cognition and childhood neurodevelopment , and is hypothesized to be partly driven by epigenetic modifications. However, it remains unknown whether some of these associations are already evident during foetal development. Similar biological signals shape the developmental processes in the foetal brain and placenta.Therefore, we hypothesize that green space can modify epigenetic processes of cognition-related pathways in placental tissue, such as DNA-methylation of the serotonin receptor HTR2A. HTR2A-methylation was determined within 327 placentas from the ENVIRONAGE (ENVIRonmental influence ON early AGEing) birth cohort using bisulphite-PCR-pyrosequencing. Total green space exposure was calculated using high-resolution land cover data derived from the Green Map of Flanders in seven buffers (50 m-3 km) and stratified into low (<3 m) and high (≥3 m) vegetation. Residential nature was calculated using the Land use Map of Flanders. We performed multivariate regression models adjusted for several a priori chosen covariables. For an IQR increment in total green space within a 1,000 m, 2,000 m and 3,000 m buffer the methylation of HTR2A increased with 1.47% (95%CI:0.17;2.78), 1.52% (95%CI:0.21;2.83) and 1.42% (95%CI:0.15;2.69), respectively. Additionally,, we found 3.00% (95%CI:1.09;4.91) and 1.98% (95%CI:0.28;3.68) higher HTR2A-methylation when comparing residences with and without the presence of nature in a 50 m and 100 m buffer, respectively. The methylation status of HTR2A in placental tissue is positively associated with maternal green space exposure. Future research is needed to understand better how these epigenetic changes are related to functional modifications in the placenta and the consequent implications for foetal development.

KEYWORDS:

• Green space
• placenta
• DNA methylation
• HTR2A
• serotonin
• epigenetic

Acknowledgments

The ENVIRONAGE birth cohort was established by the EU research council “project ENVIRONAGE” (ERC-2012-StG 310,890) and received support for this study from the Flemish Scientific Fund (G073315N/G048420N), from the Belgian Science Policy Office BELSPO (grant nr. BR/154/A1/RespirIT) and Kom op Tegen Kanker. Further, Esmée M Bijnens holds a fellowship from the Marguerite-Marie Delacroix foundation.

Data availability statement

The data that support the findings of this study are available from the corresponding author upon reasonable request. https://www.uhasselt.be/nl/aparte-sites-uhasselt/limburgs-geboortecohort

Disclosure statement

No potential conflict of interest was reported by the author(s).

supplementary material

Supplemental data for this article can be accessed online at https://doi.org/10.1080/15592294.2022.2088464

Additional information

Funding

This work was supported by the BELSPO [BR/154/A1/RespirIT]; Research Foundation Flanders [12I1517N]; Research Foundation Flanders [G073315N]; Research Foundation Flanders [ERC-2012-StG 310,890]; Research Foundation Flanders [G048420N];Marguerite Marie Delacroix;