Investigating epigenetic changes in the human placenta in response to periconceptional environment

Sainty, Becky (2025) Investigating epigenetic changes in the human placenta in response to periconceptional environment. Doctoral thesis, University of East Anglia.

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Abstract

The placenta plays an important role in shaping early development; issues with placenta function link to both pregnancy complications and adverse health outcomes later in life. Imprinted genes play an important role, placenta-specific imprinted genes often display polymorphic DNA methylation and cell-type specificity. In this thesis, I first optimise a protocol to separate trophoblast and fibroblasts from placenta tissue. These then confirm trophoblast-specific DNA methylation at novel loci PIK3R1 and within the KCNQ1 region.

Metastable epialleles (MEs) vary in DNA methylation between but not within individuals. Their response to periconceptional environment has been demonstrated by higher DNA methylation in blood from children conceived in the Gambian rainy season. This has been linked to seasonal variation in dietary components required for one-carbon metabolism, and thus producing methyl groups. I demonstrate DNA methylation only conserved in 27% of putative MEs in the human placenta compared to somatic tissue in a UK cohort. In Gambian placentas, DNA methylation at MEs does not change with season of conception. However, DNA methylation at placenta-specific imprinted genes, and to a lesser extent ubiquitous imprinted genes, is higher in placentas from rainy season conceptions. The change is a combination of both average DNA methylation and increasing polymorphism.

I then explore one-carbon metabolism placentas from The Gambia. I find increased expression from dry season conceptions at two genes related to folate transport, FOLR2 and FPGS. Finally, I find expression of imprinted genes is altered in intrauterine growth restriction placentas, in line with previous studies. There are also changes to one-carbon metabolism, with decreased expression of MTHFD1L, a folate cycle enzyme, and increased expression of LMBRD1, a B12 transporter. Together, this demonstrates periconceptional environment can influence DNA methylation at imprinted genes in the placenta, and this may be linked to availability of one-carbon metabolism components.

Item Type:	Thesis (Doctoral)
Faculty \ School:	Faculty of Science > School of Biological Sciences
Depositing User:	Chris White
Date Deposited:	18 Jun 2026 10:58
Last Modified:	18 Jun 2026 10:58
URI:	https://ueaeprints.uea.ac.uk/id/eprint/103432
DOI:

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