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

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Perez-Garcia, Vicente  ORCID logo
Kieckbusch, Jens 
Wang, Xiaoqiu 
DeMayo, Francesco 


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.



Age Factors, Aging, Animals, Cells, Cultured, Decidua, Embryonic Development, Female, Gene Expression Profiling, Humans, Male, Maternal Age, Mice, Inbred C57BL, Placenta, Placentation, Pregnancy, Pregnancy Complications, Reproduction, Uterus

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Nat Commun

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Springer Science and Business Media LLC
Wellcome Trust (200841/Z/16/Z)
This work was supported by the Biotechnology and Biological Sciences Research Council (Strategic Programme Grant BB/J004499/1) and by the Centre for Trophoblast Research, University of Cambridge, UK. L.W. is supported by a Medical Research Council DTP studentship and J.K. is the recipient of a Next-Generation Fellowship awarded by the Centre for Trophoblast Research, University of Cambridge, UK.