Periodic Reporting for period 1 - NeuroAPA (Neurodevelopmental outcome in offspring conceived by parents at advanced parental age)
Período documentado: 2019-04-01 hasta 2021-03-31
Since 1970s, social and economic factors (i.e. expansion of higher education, lifestyle, and economic wellbeing) lead to postponement of parenthood above age of 35. It is now estimated that the rate of first childbearing at advanced maternal age has reached 30% and that at advanced paternal age over 45%, in most developed countries. Current data from epidemiological reports identified advanced parental age as risk factor for pregnancy complications and for the onset of neurological and/or psychiatric disorders (e.g. autism, schizophrenia) in the offspring. However, how and at what extent advanced parental age may contribute to a poorer neurological/psychiatric outcome is still poorly described. In this context, the general aim of NeuroAPA was to contribute to our understanding of the mechanism behind the increased incidence of neurodevelopmental disorders in offspring conceived by aged parents. The work carried out within the project showed an association between conception at advanced age and pregnancy complications (e.g. miscarriage, peri-natal mortality) and identified epigenetic changes in the spermatozoa as candidate mechanisms behind the observed side effect of conception at advanced paternal age.
The NeuroApa project investigated the influence of conception at advanced on pregnancy progression and the health of the offspring in the mouse model age (> 8 months-age in the mouse corresponds to > 40 years in humans). The results obtained within the project: i) confirmed the increased risk of pregnancy complication (e.g. pregnancy lost, delivery complication) following conception at advanced age in a mouse model; ii) showed increased risk of perinatal mortality in offspring from aged parents; and iii) showed a weak association between advanced parental age on anxiety-like and repetitive behaviour in the offspring, which are traits associated with neurodevelopmental disorders. To better clarify how paternal age might contribute to poor pregnancy outcome, we analysed mouse spermatozoa from subjects between 2 and 15 months of age (corresponding to human age from 20 years to > 65 years). Our data showed that aging did not influence sperm viability and metabolism while caused changes in the DNA epigenetic marks and conformation. These changes in the sperm DNA can be passed to the embryos and significantly affect the further stages of development during the pregnancy and after birth. The data obtained by NeuroApa enhanced our understanding of the risk associated with the conception at advanced age. Even if it will not be possible to reverse this trend in our society, knowing all the risk as well as the mechanisms mediating the side-effects associated with conception at advanced age can i) help to define new counselling strategies as well as early diagnostic approaches, ii) contribute to reduce the economic/social burden associated to postponement of parenthood, and iii) improve the quality of life of both parents and children. The project resulted in three scientific publications (2 research articles and 1 review) and was promoted within the general public through various channels (social media, press release, interviews).
NeuroAPA contributed to enhance our understanding of the influence of aging on pregnancy progression and postnatal development and suggest epigenetic changes in the gametes as one of key mechanisms behind side effects associated with conception at advanced age. Even if it will not be possible to reverse the trend, knowing all the risk as well as the mechanisms mediating the side-effects associated with conception at advanced age can i) help to define new counselling strategies as well as early diagnostic approaches, ii) contribute to reduce the economic/social burden associated to postponement of parenthood, and iii) improve the quality of life of both parents and children.