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Older wombs linked to complications in pregnant mice

Increased risk of pregnancy complications for older mothers might be linked to poor placental growth...

A decision to start a family later in life could be about more than just the age of your eggs. A new study in mice suggests the age of a mother's womb may also have a part to play. Research led by Myriam Hemberger PhD, at the Epigenetics Program, The Babraham Institute, Babraham Research Campus, Cambridge, UK, is one of the first programs to look at the affects of maternal age on womb health and is expected to lead to new research in human pregnancy.
Many of the complications during pregnancy all increase with age and have been linked to the deteriorating quality of ageing egg cells. Yet the new research published in Nature Communications, reveals that older wombs also have more trouble adapting to pregnancy.

By examining first pregnancies in aged mice, the team showed that in mice as in humans, the risk of birth complications increases with age. Closer examination revealed that wombs of older mice were less able to support growth of the placenta, leading to poorer blood supply for the developing young, which slows growth and can cause birth defects.

Co-first authors Laura Woods and Vicente Perez-Garcia discussing their findings: "We wanted to enhance our understanding of the increased risks of pregnancy in older mothers. When we compared mice who have their first litter in middle age to their younger counterparts, we found the lining of the uterus does not respond as well to pregnancy hormones, which delays placenta formation. By identifying the key pathways affected by age in mice, we have a better idea of what to look for in humans."
Understanding the potential risks of pregnancy with age is an increasingly important issue. In the UK, more and more women are starting families later. In 2015, 53% of UK births were to women aged 30 or over. A 2016 report by the Human Fertilisation and Embryology Authority showed that freezing eggs for later use is also growing in popularity. In 2001, just 29 women opted for the treatment, rising to 816 women by 2014.

The shorter lifespan of mice makes them useful for studying the effects of age on pregnancy, but such results cannot always be directly applied to human pregnancies. Although the new research will help guide long-term studies in humans, it is not entirely clear what implications of the findings will mean for family planning and human healthcare. However, the research suggests other factors in addition to egg quality need to be considered.
"Overall, our study highlights the importance of the ageing uterine environment as a cause of reproductive decline in female mice. This is one of the first times that the considerable impact of age on pregnancy has been studied in detail beyond the effects of egg fitness. More research will be needed to establish if and how our results translate to humans."

Myriam Hemberger PhD, Epigenetics Program, The Babraham Institute, Babraham Research Campus, Cambridge; Centre for Trophoblast Research, University of Cambridge, Cambridge, UK; Lead author, and Group Leader

As a member of the Royal College of Obstetricians and Gynaecologists, Ashley Moffett, Professor of Reproductive Immunology at the University of Cambridge and expert on placenta formation, adds: "We know that the so-called Great Obstetrical Syndromes, in particular pre-eclampsia, are more common in older women but it's still not clear why. Although more work is needed to demonstrate this effect in humans, this study could help advance research into these important questions."

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.

All authors of the study: Laura Woods, Vicente Perez-Garcia, Jens Kieckbusch, Xiaoqiu Wang, Francesco DeMayo, Francesco Colucci, and Myriam Hemberger.

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Sep 6, 2017   Fetal Timeline   Maternal Timeline   News   News Archive

Fluorescent microscopy image of the womb of an elderly mouse. Areas in GREEN show cells which respond to pregnancy hormones. As a mouse ages, the womb becomes less sensitive to hormones UNEVEN, PATCHY areas of GREEN. This is reflected in the developmental problems we see in the offspring from these older mothers. Image credit: Laura Woods, Babraham Institute, Centre for Trophoblast Research, Cambridge, UK

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