The University of Southampton
University of Southampton Institutional Repository

High maternal folic acid intake around conception alters mouse blastocyst lineage allocation and expression of key developmental regulatory genes

High maternal folic acid intake around conception alters mouse blastocyst lineage allocation and expression of key developmental regulatory genes
High maternal folic acid intake around conception alters mouse blastocyst lineage allocation and expression of key developmental regulatory genes

Folate, a cofactor for the supply of one-carbon groups, is required by epigenetic processes to regulate cell lineage determination during development. The intake of folic acid (FA), the synthetic form of folate, has increased significantly over the past decade, but the effects of high periconceptional FA intake on cell lineage determination in the early embryo remains unknown. Here, we investigated the effect of maternal high FA (HFA) intake on blastocyst development and expression of key regulatory genes. C57BL/6 adult female mice were fed either Control diet (1 mg FA) for 4 weeks before conception and during the preimplantation period (Con-Con); Control diet for 4 weeks preconception, followed by HFA (5 mg FA) diet during preimplantation (Con-HFA); or HFA diet for 4 weeks preconception and during preimplantation (HFA-HFA). At E3.5, blastocyst cell number, protein, and mRNA expression were measured. In HFA-HFA blastocysts, trophectoderm cell numbers and expression of CDX2, Oct-4, and Nanog were reduced compared with Con-Con blastocysts; Con-HFA blastocysts showed lower CDX2 and Oct-4 expression than Con-Con blastocysts. These findings suggest periconceptional HFA intake induces changes in key regulators of embryo morphogenesis with potential implications for subsequent development.

Cdx2, blastocyst, epigenetics, folic acid, trophectoderm
1040-452X
261-273
Penailillo, R. S.
1c5fb85f-4d7e-4c9c-b2fb-66b11da72d9d
Burton, M. A.
250319ad-90dc-4651-b118-d5dbe5eaafa6
Burdge, G. C.
09d60a07-8ca1-4351-9bf1-de6ffcfb2159
Fleming, T. P.
2abf761a-e5a1-4fa7-a2c8-12e32d5d4c03
Lillycrop, K. A.
eeaaa78d-0c4d-4033-a178-60ce7345a2cc
Penailillo, R. S.
1c5fb85f-4d7e-4c9c-b2fb-66b11da72d9d
Burton, M. A.
250319ad-90dc-4651-b118-d5dbe5eaafa6
Burdge, G. C.
09d60a07-8ca1-4351-9bf1-de6ffcfb2159
Fleming, T. P.
2abf761a-e5a1-4fa7-a2c8-12e32d5d4c03
Lillycrop, K. A.
eeaaa78d-0c4d-4033-a178-60ce7345a2cc

Penailillo, R. S., Burton, M. A., Burdge, G. C., Fleming, T. P. and Lillycrop, K. A. (2021) High maternal folic acid intake around conception alters mouse blastocyst lineage allocation and expression of key developmental regulatory genes. Molecular Reproduction and Development, 88 (4), 261-273. (doi:10.1002/mrd.23462).

Record type: Article

Abstract

Folate, a cofactor for the supply of one-carbon groups, is required by epigenetic processes to regulate cell lineage determination during development. The intake of folic acid (FA), the synthetic form of folate, has increased significantly over the past decade, but the effects of high periconceptional FA intake on cell lineage determination in the early embryo remains unknown. Here, we investigated the effect of maternal high FA (HFA) intake on blastocyst development and expression of key regulatory genes. C57BL/6 adult female mice were fed either Control diet (1 mg FA) for 4 weeks before conception and during the preimplantation period (Con-Con); Control diet for 4 weeks preconception, followed by HFA (5 mg FA) diet during preimplantation (Con-HFA); or HFA diet for 4 weeks preconception and during preimplantation (HFA-HFA). At E3.5, blastocyst cell number, protein, and mRNA expression were measured. In HFA-HFA blastocysts, trophectoderm cell numbers and expression of CDX2, Oct-4, and Nanog were reduced compared with Con-Con blastocysts; Con-HFA blastocysts showed lower CDX2 and Oct-4 expression than Con-Con blastocysts. These findings suggest periconceptional HFA intake induces changes in key regulators of embryo morphogenesis with potential implications for subsequent development.

Text
High FA intake MRD 2.0 UNMarked version - Accepted Manuscript
Download (2MB)

More information

Accepted/In Press date: 20 February 2021
e-pub ahead of print date: 15 March 2021
Published date: 22 April 2021
Keywords: Cdx2, blastocyst, epigenetics, folic acid, trophectoderm

Identifiers

Local EPrints ID: 449679
URI: http://eprints.soton.ac.uk/id/eprint/449679
ISSN: 1040-452X
PURE UUID: 79b7519f-c21f-430b-bd0d-fe2c34396403
ORCID for M. A. Burton: ORCID iD orcid.org/0000-0002-7117-8151
ORCID for G. C. Burdge: ORCID iD orcid.org/0000-0002-7665-2967
ORCID for K. A. Lillycrop: ORCID iD orcid.org/0000-0001-7350-5489

Catalogue record

Date deposited: 10 Jun 2021 16:32
Last modified: 11 Jul 2024 04:06

Export record

Altmetrics

Contributors

Author: R. S. Penailillo
Author: M. A. Burton ORCID iD
Author: G. C. Burdge ORCID iD
Author: T. P. Fleming
Author: K. A. Lillycrop ORCID iD

Download statistics

Downloads from ePrints over the past year. Other digital versions may also be available to download e.g. from the publisher's website.

View more statistics

Atom RSS 1.0 RSS 2.0

Contact ePrints Soton: eprints@soton.ac.uk

ePrints Soton supports OAI 2.0 with a base URL of http://eprints.soton.ac.uk/cgi/oai2

This repository has been built using EPrints software, developed at the University of Southampton, but available to everyone to use.

We use cookies to ensure that we give you the best experience on our website. If you continue without changing your settings, we will assume that you are happy to receive cookies on the University of Southampton website.

×