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Lookup NU author(s): Dr Miguel Velazquez
This work is licensed under a Creative Commons Attribution 4.0 International License (CC BY 4.0).
Advanced maternal age (AMA) is known to reduce fertility, increases aneuploidy in oocytes and early embryos and leads to adverse developmental consequences which may associate with offspring lifetime health risks. However, investigating underlying effects of AMA on embryo developmental potential is confounded by the inherent senescence present in maternal body systems further affecting reproductive success. Here, we describe a new model for the analysis of early developmental mechanisms underlying AMA by the derivation and characterisation of mouse embryonic stem cell (mESC-like) lines from naturally conceived embryos. Young (7–8 weeks) and Old (7–8 months) C57BL/6 female mice were mated with young males. Preimplantation embryos from Old dams displayed developmental retardation in blastocyst morphogenesis. mESC lines established from these blastocysts using conventional techniques revealed differences in genetic, cellular and molecular criteria conserved over several passages in the standardised medium. mESCs from embryos from AMA dams displayed increased incidence of aneuploidy following Giemsa karyotyping compared with those from Young dams. Moreover, AMA caused an altered pattern of expression of pluripotency markers (Sox2, OCT4) in mESCs. AMA further diminished mESC survival and proliferation and reduced the expression of cell proliferation marker, Ki-67. These changes coincided with altered expression of the epigenetic marker, Dnmt3a and other developmental regulators in a sex-dependent manner. Collectively, our data demonstrate the feasibility to utilise mESCs to reveal developmental mechanisms underlying AMA in the absence of maternal senescence and with reduced animal use.
Author(s): Khurana P, Smyth N, Sheth B, Velazquez MA, Eckert JJ, Fleming TP
Publication type: Article
Publication status: Published
Journal: Journal of Developmental Origins of Health and Disease
Pages: Epub ahead of print
Online publication date: 01/07/2021
Acceptance date: 16/05/2021
Date deposited: 01/07/2021
ISSN (print): 2040-1744
ISSN (electronic): 2040-1752
Publisher: Cambridge University Press
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