Theme 4:

Later life effects of developmental mismatch

 

 

Of intellectual and practical necessity much of our research focuses on individual outcomes, and in this theme we focus on systems where we have particular expertise, while being mindful that many outcomes are integrated and interdependent as a result of adaptive responses and life history tradeoffs. Some of the outcomes of clinical and agricultural interest result primarily from immediately adaptive responses and are exhibited in the neonatal or infant period (e.g. prematurity, fetal growth retardation); others appear later in life as altered phenotypes that may affect production characteristics, or (in mismatched environments) lead to increased disease risk.

 

We are continuing our research into how environmental influences can lead to alterations in the trajectory of fetal growth and maturation, or lead to premature activation of the signalling cascades that lead to birth. We are also testing the hypothesis that patterns of maternal-infant interaction are themselves programming stimuli.

 

Our studies of the mismatch pathway have revealed an important interaction between the degree of prenatal compromise and postnatal energy availability.  We have also suggested why the tempo of pubertal maturation might be affected, and have data to support this in sheep, rat, and human.  A key issue is what determines the altered distribution of nutrients between muscle and fat, leading to compensatory central obesity.  Our ongoing studies in rats use a range of inducers and outcomes with amplifying and reversing approaches to dissect these issues.

 

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Current projects

 

1. Effects of nutrition and care on processes underlying the tempo of reproductive development and fecundity: an intergenerational study

 

This is an experimental project investigating the relationship between early life nutrition and reproduction, and how changes may be transmitted to subsequent generations. Previous work by this group has shown in both humans and in rats that fetal adaptations to poor nutrition advances pubertal onset, highlighting the importance of prenatal and postnatal interactions in influencing reproductive strategies. New studies have suggested that poor maternal care and bonding can also impact on reproductive maturation. This project seeks to elucidate the underlying mechanisms regulating accelerated pubertal onset in rats that were nutritionally challenged as fetuses and infants, and to investigate how poor maternal care during early neonatal life may play a role in reproductive maturation.

 

Deborah Sloboda

Project leader: Dr Deborah Sloboda (d.sloboda <at> auckland.ac.nz)

Project team: Dr Kristin Connor, Dr Mark Vickers, Zoe Clayton (MSc student), Cassandra Yap (MSc student)

 

Deborah can be heard talking about her research on YouTube.

 

 

2. Epigenetic regulation of the activities of key genes required for parturition, fetal wellbeing and long-term health

 

This is an experimental project that aims to determine the critical epigenetic changes that herald the onset of labour and membrane rupture, as well as those that lead to specific pathologies such as preterm labour and intrauterine growth restriction. This project will use placental and umbilical cord tissues, as well as cell-line model systems, to investigate how the epigenetic status of intrauterine tissues can influence major processes of pregnancy.

 

Murray Mitchell

Project leader: Prof Murray Mitchell (left; m.mitchell <at> auckland.ac.nz)

Project team: Dr Mhoyra Fraser, Dr Allan Sheppard

 

 

3. Empirical evidence to support the DOHaD paradigm: Maternal high fat nutrition and the role of leptin in the etiology of programming-related metabolic disorders

 

This is an experimental animal project investigating the effects of a maternal high-fat diet on metabolism and the onset of obesity in the offspring. This project uses a model of nutrition that was previously established with NRCGD funding to expand on the underlying mechanisms that associate an adverse prenatal environment with metabolic dysfunction in later life. These studies will incorporate quantitative gene expression and epigenetic profiling analyses using the Sequenom platform, as well as linkages with molecular platforms in Southampton, Singapore and Cambridge.

 

Mark Vickers

Project leader: Dr Mark Vickers (m.vickers <at> auckland.ac.nz)

Project team: Dr Kristin Connor, Dr Deborah Sloboda, Graham Howie (PhD student)

 

 

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