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Nat Commun. 2017 Sep 5;8(1):352. doi: 10.1038/s41467-017-00308-x.

Decidualisation and placentation defects are a major cause of age-related reproductive decline.

Author information

1
Epigenetics Programme, The Babraham Institute, Babraham Research Campus, Cambridge, CB22 3AT, UK.
2
Centre for Trophoblast Research, University of Cambridge, Downing Street, Cambridge, CB2 3EG, UK.
3
Department of Obstetrics and Gynaecology, University of Cambridge School of Clinical Medicine, NIHR Cambridge Biomedical Research Centre, Addenbrooke's Hospital, Box 111, Hills Road, Cambridge, CB2 0SP, UK.
4
Reproductive and Developmental Biology Laboratory, NIEHS, Research Triangle Park, Durham, NC, 27709, USA.
5
Epigenetics Programme, The Babraham Institute, Babraham Research Campus, Cambridge, CB22 3AT, UK. myriam.hemberger@babraham.ac.uk.
6
Centre for Trophoblast Research, University of Cambridge, Downing Street, Cambridge, CB2 3EG, UK. myriam.hemberger@babraham.ac.uk.

Abstract

Mammalian reproductive performance declines rapidly with advanced maternal age. This effect is largely attributed to the exponential increase in chromosome segregation errors in the oocyte with age. Yet many pregnancy complications and birth defects that become more frequent in older mothers, in both humans and mice, occur in the absence of karyotypic abnormalities. Here, we report that abnormal embryonic development in aged female mice is associated with severe placentation defects, which result from major deficits in the decidualisation response of the uterine stroma. This problem is rooted in a blunted hormonal responsiveness of the ageing uterus. Importantly, a young uterine environment can restore normal placental as well as embryonic development. Our data highlight the pivotal, albeit under-appreciated, impact of maternal age on uterine adaptability to pregnancy as major contributor to the decline in reproductive success in older females.Advanced maternal age has been associated with lower reproductive success and higher risk of pregnancy complications. Here the authors show that maternal ageing-related embryonic abnormalities in mouse are caused by decidualisation and placentation defects that can be rescued by transferring the embryo from an old to a young uterus.

PMID:
28874785
PMCID:
PMC5585348
DOI:
10.1038/s41467-017-00308-x
[Indexed for MEDLINE]
Free PMC Article

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