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Reproductive Origins of Adult Health and Disease (ROAHD)

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In the program, ROAHD researchers are studying factors that influence the health of mother, father and child before, during and after pregnancy. These can be lifestyle factors, like smoking, drinking, and the use of medication before and during pregnancy, but also factors like disease, stress, and nutrition. Long term molecular and biological effects of these factors are investigated in for instance placental material and cord blood.

Programme Leaders   Mission and Description of the Programme  

Mission
The mission of the programme is to understand the effects of paternal and maternal determinants (including  genetics, nutrition, environmental factors, disease, stress and interventions prior or during pregnancy) on the developmental process from gamete to adult.

The major objectives of the programme can be grouped in four main topics:

  1. Investigating paternal and maternal preconceptional, preimplantation and pregnancy-related determinants and predictors of future health and disease of the mother, gametes and offspring;
  2. Investigating screening and diagnostic procedures before conception and during pregnancy to identify disease, or disease risk, in the mother, gametes and offspring;
  3. Exploring interventions before conception and during pregnancy to promote the health for the future child and mother; and
  4. Conducting implementation research for evidence on optimal perinatal care in practice.

 

Description of the programme
The importance of this field of research in the framework of healthy ageing is emphasized by the UMCG on their website as follows: “Healthy Ageing is a lifelong process that starts even before conception, with parents who pass on their genes and with them the risks and opportunities for a healthy life course, or the occurrence of illness later in life”.

Healthy ageing starts before conception and is further determined during embryonic and fetal life. Growth and development of the future adult is affected by genetic and epigenetic programming of gametes and preimplantation embryos. The “Barker Hypothesis” suggests that several diseases in adulthood such as cardiovascular disease, diabetes, lung disease and possibly psychiatric vulnerability have their origin during pregnancy. An unfavorable intra-uterine environment can be caused by lifestyle factors such as drug exposure, alcohol consumption, smoking, unhealthy diet, overweight and chronic psychological stress and may lead to changes that can have a permanent impact on the structure, function, physiology and metabolism of the placenta and the fetus. Eventually, potentially unfavorable environments affect fetal organ development and gene expression and result in an adult with a greater susceptibility to the development of chronic disease later in life. It is not only the future child who has an increased risk of health problems, but also the mother who has pre-existing diseases or who develops pregnancy-related diseases such as pre-eclampsia is at increased risk for health problems in the future (i.e. hypertension, diabetes cardiovascular- and renal disease). Investigating mechanisms and factors that are responsible for changes in placental function and maternal physiology can help us to understand the changes that occur in the fetus and the future adult, and the mother. Cohort studies, follow up studies of interventions prior to pregnancy or during pregnancy, as well as animal experimental models within the ROAHD programme will help to elucidate both associations and pathophysiological mechanisms.

Current research comprises various activities in the three broad domains:

  1. Preconception/preimplantation research concerns gametes prior to conception and implantation when they are susceptible to influences of parental origin and the environment. This can have consequences for the development of the embryo and the health of the future individual. The overall aim is to always optimize pregnancy outcomes.
  2. The specific domain of pregnancy concerns issues resulting from the fact that after implantation, the dynamic epigenetic, immunologic and metabolic processes in the intimate and reciprocal interaction between mother, placenta and fetus determine fetal development and course of pregnancy. Investigating determinants and epigenetic consequences of pregnancy-associated diseases such as hypertensive disorders (pre-eclampsia), diabetes in pregnancy and placental disorders, including development of techniques for early diagnosis and intervention in both animal and human models.
  3. Perinatal morbidity and mortality in the northern provinces of the Netherlands are above the national average and urgently require improvement. The organization of healthcare for pregnant couples needs scientific evaluation and evidence-based strategies to improve perinatal outcome for both mother and child. This will be done by investigation screening and diagnostic procedures before conception and during pregnancy to identify disease, or disease risk, in the mother, gametes and offspring and by conducting implementation research for optimal perinatal care in practice.
Relevance to Healthy Ageing  

“Healthy ageing is a lifelong process that starts even before conception, with parents who pass on their genes and with them the risks and opportunities for a healthy life course, or the occurrence of illness later in life”. This quote from the UMCG website outlines the importance of reproductive health for healthy ageing. Indeed, healthy ageing starts before conception and is further determined during embryonic and fetal life. Growth and development of the future adult is affected by genetic and epigenetic programming of gametes and pre-implantation embryos. These processes are still poorly understood in vivo, but evidence exists that they are influenced in vitro by assisted reproduction technologies.  Maternal factors determine the metabolic and endocrine environment in utero during pregnancy, and also influence the growth and development of the fetus. The so-called “Barker Hypothesis” suggests that several diseases in adulthood such as cardiovascular diseases, diabetes, lung diseases and possibly psychiatric vulnerability find their origin during pregnancy. An unfavorable intra-uterine environment can be caused by lifestyle factors such as drug exposure, alcohol consumption, smoking, unhealthy diet, overweight and chronic psychological stress and may lead to changes that can have a permanent impact on the structure, function, physiology and metabolism of the placenta and the fetus. Eventually, this unfavorable environment affects fetal organ development and gene expression and results in  an adult with a greater susceptibility for the development of the  chronic diseases later in life. Not only the future child has an increased risk for health problems, but also the mother who has pre-existing  diseases or who develops pregnancy related diseases such as preeclampsia has an increased risk for health problems in her future (i.e. hypertension, diabetes cardiovascular- and renal diseases). Investigating mechanisms and factors that are responsible for changes in placenta function and maternal physiology  can help to understand the changes that occur in the fetus and the “future adult”, and the mother.

An example of ROAHD’s research projects   

Long term effects of pregnancy complications on the child’s health
Researcher: Torsten Plösch

ROAHD is concerned with aspects such as early foetal development and pregnancy in relation to the health of the child, the adolescent and the adult. The prestigious ZonMw (The Netherlands Organisation for Health Research and Development) TOP subsidy, recently awarded to Torsten Plösch PhD, strongly supports the UMCG’s research into these aspects as well as the influence of an abnormal pregnancy on health later in life. Plösch’s research is embedded into the research of the subdepartment Obstetrics at the UMCG, in close cooperation with Sicco Scherjon PhD.
Pre-eclampsia occurs in 5% of all pregnancies and is one of the major – maternal – complications in pregnancies in the Western world. Pre-eclampsia is a mother’s disease (the mother has high blood pressure and protein in the urine), but the disorder often has major effects on the placenta. For instance, it can slow down the foetus’ growth. Children whose growth slowed down during the pregnancy are often known to have health problems at a later age. The exact cause is unknown.
We think this may be linked to changes in the epigenome. The epigenome gives instructions on reading DNA: it determines which and how many genes have to be read and which should not. The epigenome is influenced by factors like food, toxic substances (and other environmental factors), but also by stress. In this project we investigate whether the mother’s pre-eclampsia affects the epigenome of placenta and child, both in guinea pigs and in humans. We expect that these changes play a central role in the long-term negative effects of pre-eclampsia on the child’s health.
With this research we hope to gain more insight into the relation between pregnancy complications and health at a later age and to find possible strategies to prevent health deterioration.

Principal Investigators / nr of PhD students