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Development. 2020 Mar 17;147(6). pii: dev185629. doi: 10.1242/dev.185629.

Epigenetic changes occur at decidualisation genes as a function of reproductive ageing in mice.

Woods L1,2, Morgan N1,2, Zhao X3, Dean W3,4,5, Perez-Garcia V1,2, Hemberger M6,2,4,5,7.

Author information

1
Epigenetics Programme, The Babraham Institute, Babraham Research Campus, Cambridge CB22 3AT, UK.
2
Centre for Trophoblast Research, University of Cambridge, Tennis Court Road, Cambridge CB2 3DY, UK.
3
Dept. of Cell Biology and Anatomy, Cumming School of Medicine, University of Calgary, Calgary, AB T2N 4N1, Canada.
4
Alberta Children's Hospital Research Institute, University of Calgary, Calgary, AB T2N 4N1, Canada.
5
Dept. of Biochemistry & Molecular Biology, Cumming School of Medicine, University of Calgary, Calgary, AB T2N 4N1, Canada.
6
Epigenetics Programme, The Babraham Institute, Babraham Research Campus, Cambridge CB22 3AT, UK myriam.hemberger@ucalgary.ca.
7
Dept. of Medical Genetics, Cumming School of Medicine, University of Calgary, Calgary AB T2N 4N1, Canada.

Abstract

Reproductive decline in older female mice can be attributed to a failure of the uterus to decidualise in response to steroid hormones. Here, we show that normal decidualisation is associated with significant epigenetic changes. Notably, we identify a cohort of differentially methylated regions (DMRs), most of which gain DNA methylation between the early and late stages of decidualisation. These DMRs are enriched at progesterone-responsive gene loci that are essential for reproductive function. In female mice nearing the end of their reproductive lifespan, DNA methylation fidelity is lost at a number of CpG islands (CGIs) resulting in CGI hypermethylation at key decidualisation genes. Importantly, this hypermethylated state correlates with the failure of the corresponding genes to become transcriptionally upregulated during the implantation window. Thus, age-associated DNA methylation changes may underlie the decidualisation defects that are a common occurrence in older females. Alterations to the epigenome of uterine cells may therefore contribute significantly to the reproductive decline associated with advanced maternal age.

KEYWORDS:

Ageing; CpG islands; DNA methylation; Decidua; Epigenetics; Reproduction

PMID:
32184271
DOI:
10.1242/dev.185629

Conflict of interest statement

Competing interestsThe authors declare no competing or financial interests.

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