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Dynamic expression of TET1, TET2, and TET3 dioxygenases in mouse and human placentas throughout gestation.

Accepted version
Peer-reviewed

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Authors

Rakoczy, Joanna 
Padmanabhan, Nisha 
Krzak, Ada M 
Kieckbusch, Jens 
Cindrova-Davies, Tereza  ORCID logo  https://orcid.org/0000-0002-9212-0514

Abstract

INTRODUCTION: Throughout pregnancy, the placenta dynamically changes as trophoblast progenitors differentiate into mature trophoblast cell subtypes. This process is in part controlled by epigenetic regulation of DNA methylation leading to the inactivation of 'progenitor cell' genes and the activation of 'differentiation' genes. TET methylcytosine dioxygenases convert 5-methylcytosine (5-mC) to 5-hydroxymethylcytosine (5-hmC) during DNA demethylation events. Here, we determine the spatiotemporal expression of TET1, TET2, and TET3 in specific trophoblast cell populations of mouse and human placentas throughout gestation, and consider their role in trophoblast cell differentiation and function. METHODS: In situ hybridization analysis was conducted to localize Tet1, Tet2, and Tet3 mRNA at key stages of mouse placental development. The distribution of 5-mC and 5-hmC in these samples was also evaluated. In comparison, expression patterns of TET1, TET2, and TET3 protein in human placentas were determined in first trimester and term pregnancies. RESULTS: In mouse, Tet1-3 mRNA was widely expressed in trophoblast cell populations from embryonic (E) day 8.5 to E12.5 including in progenitor and differentiated cells. However, expression became restricted to specific trophoblast giant cell subtypes by late gestation (E14.5 to E18.5). This coincided with cellular changes in 5-mC and 5-hmC levels. In human, cell columns, extravillous trophoblast and syncytiotrophoblast expressed TET1-3 whereas only TET3 was expressed in villus cytotrophoblast cells in first trimester and term placentas. DISCUSSION: Altogether, our data suggest that TET enzymes may play a dynamic role in the regulation of transcriptional activity of trophoblast progenitors and differentiated cell subtypes in mouse and human placentas.

Description

Keywords

5-Hydroxymethylcytosine, 5-Methylcytosine, DNA methylation, Placenta development, Trophoblast, 5-Methylcytosine, Animals, DNA-Binding Proteins, Dioxygenases, Female, Humans, Mice, Mixed Function Oxygenases, Placenta, Pregnancy, Proto-Oncogene Proteins

Journal Title

Placenta

Conference Name

Journal ISSN

0143-4004
1532-3102

Volume Title

59

Publisher

Elsevier BV
Sponsorship
Lister Institute of Preventive Medicine
Royal Society (NF150004)