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A study by University of Manchester scientists has revealed some of the mechanisms which may explain why older mice are more likely to give birth to offspring that have not grown to their full potential in the womb. 

The study in older animals  showed that the placentas of male but not female offspring had increased cell damage from a biological state called oxidative stress. 

Oxidative stress occurs when harmful molecules called free radicals build up faster than the body can clear them. 

It is associated with a range of pregnancy complications including fetal growth restriction and preeclampsia, both of which increase the risk of stillbirth. 

The study demonstrated reduced weight in both female and male fetuses in older mice, but the placental alterations were sex-specific. 

The scientists are conducting further studies in mice to confirm these findings  and also carrying out a parallel study to see if similar sex differentiated mechanisms exist in human placentas from mothers of advanced maternal age (AMA), defined as age 35 and over. 

The study, published in the journal Reproduction and funded by Tommy鈥檚 and the Medical Research Council, also discovered placental mitochondria -  the biological batteries that power cells-  were working at a reduced rate in the placentas of both male and female pups but that there were more of them. 

Mitochondria are a major source of free radicals. Reducing their rate of activity at the same time as increasing their numbers is a way they adapt to prevent further oxidative stress while maintaining the supply of energy needed for cells to work properly.

This could mean that the adaptation in placentas from females was more successful than in placentas from males because oxidative stress was not increased in placentas from females of older mice. 

Although scientists know AMA increases the risk of placental dysfunction leading to  fetal growth restriction and stillbirth, little is known about the mechanisms that cause it.

Lead author Dr Michelles Desforges from the University of Manchester  said: 鈥淪ome impacts of advanced maternal age appear common to both sexes but this data suggests some may be sex specific.

鈥淓vidence that sex differentiated placental dysfunction occurs in a range of risk groups -  including diabetes or obesity- has been around for some time.

鈥淭his, however, is amongst the few to delve into the sex differentiated processes which increase the risks of adverse pregnancy outcome in animals of advanced maternal age.

鈥淚n 1980, only around 6% of pregnant women in the UK were aged 35 and over. However this figure has now risen to 25%. This represents a massive societal shift and it is important that we understand the reasons why these pregnancies are more vulnerable to fetal growth restriction and stillbirth.

鈥淏ut it is important to stress, however, that though advanced maternal age comes with  increased risks for some women, the  majority of mums aged 35 and over have normal pregnancies and healthy babies.鈥�

Principle investigator Dr Mark Dilworth added: 鈥淪tudies in mice are particularly helpful as they allow us to compare male and female offspring in the same pregnancy. In addition, these studies provide an important basis for future studies intent on developing therapeutic strategies for preventing fetal growth restriction and stillbirth.鈥�

• Sex-specific alterations in placental mitochondria, oxidative damage and apoptosis in mice of advanced maternal age鈥� is available .DOI: