School of Veterinary Medicine and Science
   
   
  
 

Image of Richard Lea

Richard Lea

Reader & Associate Professor of Reproductive Biology, Faculty of Medicine & Health Sciences

Contact

  • workRoom B27 Veterinary Academic Building
    Sutton Bonington Campus
    Sutton Bonington
    Leicestershire
    LE12 5RD
    UK
  • work0115 951 6426
  • fax0115 951 6440

Biography

Dr Richard Lea is an Associate Professor and Reader in the School of Veterinary Medicine and Science at the University of Nottingham and a Visiting Professor in the School of Animal, Rural and Environmental Sciences at Nottingham Trent University. Dr Lea received his PhD from Sheffield Hallam University (1988) in Immunological Aspects of Implantation in the Horse after which he pursued his early post-doctoral studies with David Clark at McMaster University, Canada on immunological mechanisms that underlie the traumatic problem of recurrent first trimester pregnancy loss in the human. Further postdoctoral placements at the University of Edinburgh, UK enabled Dr Lea to extend his work into endocrine and immune influences on human uterine cells after which he took up a tenured post at the Rowett Research Institute, Aberdeen, UK where he focussed on nutritional influences on intra-uterine 'immuno-endocrine' mechanisms essential for fetal development using both rodent and sheep models. For the past two decades, Dr Lea's research has focussed on the vexing and topical issue of endocrine disrupting chemicals on mammalian fertility and reproductive well-being.This area has developed substantially during his time in the vet school at the University of Nottingham.

Expertise Summary

Research Summary

Dr Lea is currently central to three internationally recognised research programs.

(1) Environmental and nutritional effects on reproduction using sheep models of human exposure and the dog as a sentinel species for the human, particularly the human infant.

(2) Causes and underlying mechanisms of pregnancy failure in domestic species.

(3) Developing surveillance systems for infectious disease in wildlife including microarray technologies to detect multiple pathogens.

Environmental and nutritional effects on reproduction.

This research programme is based on the increased incidence of testicular cancer coupled with declining sperm counts in men and an increased incidence in reproductive abnormalities at birth (cryptorchidism and hypospadias) in specific parts of the world. Together these problems are referred to as testicular dysgenesis syndrome and this has been linked to exposure to chemicals in the environment that have estrogenic, anti-androgenic or other hormone modulating activities. Much of the data to support this association has been developed in animals and similar data in humans has been more limited. Dr Lea has overcome this problem by working with ovine experimental models and canine sentinel species.

Recently there has been evidence of similar effects of environmental pollutants on female reproductive development. Ovine experimental models have been developed in which pregnant ewes have been exposed to mixtures of chemicals representative of 'real-life' exposure. This was achieved by grazing pregnant ewes on pastures fertilised with processed human-sewage sludge based fertiliser which is common global agricultural practice. Striking effects have been observed on the fetuses of these ewes including a decrease in the number of healthy follicles in the late gestation fetal ovary alongside an increased number of separately counted atretic follicles. Intriguingly, fetuses exposed during mid and late gestation exhibited more marked effects than those exposed for a period during early gestation. Dr Lea's laboratory is developing this work by looking in more detail at the male fetuses and more recently his team has established a research program on the dog as a sentinel of daily human exposure to environmental chemicals. He is one of the main drivers of an internationally acclaimed network and his mission is to use his data to heighten public awareness and impress upon government the urgent need for worldwide strategies to improve and protect global reproductive health.

Dr Lea has had considerable success in raising research funds from the European Union Framework 7 initiative. In 2008, the EU awarded 3 million euros to investigate the effects of environmental chemicals on female reproductive development and fertility and Dr Lea was a partner in this international initiative. Entitled "Reproductive effects of environmental chemicals in females: REEF" this program brought together 6 centres of excellence and the program officially ended in 2011. Considerable output was generated from this work including high impact factor papers and numerous presentations and representations at international and national conferences.

Dr Lea has recently established a research program on environmental effects on reproductive function in the dog. In collaboration with Professor England, Dr Lea has is investigating a decline in sperm quality in stud dogs which parallels the reported decline in the human. This is indicative of an environmental effect and Dr Lea and colleagues have detected a number of environmental chemicals in dog food and in adult dog testes obtained from routine veterinary castrations. Supported by funds from the Guide Dogs for the Blind Association, Dr Lea is investigating how these contaminants may effect sperm quality with the aim of improving reproductive health in dogs nationally.

Causes and underlying mechanisms of pregnancy failure in domestic species.

When abortus tissue is sent to the Veterinary Laboratories Agency (VLA) for diagnosis, only 50% of investigations reveal the most likely cause. Dr Lea is investigating this complex and multi factorial problem in terms of the range of pathogens investigated and other confounders. This program is supported by funds from the University of Nottingham under the Global Food Security initiative. This work was also a spin out project arising from the WildTech EU program described below.

Novel Technologies for Surveillance of Emerging and Re-emerging Infections of Wildlife

There is increasing concern over new emerging diseases threatening animal and human health, many of which have wildlife populations as a source and target. Considering the magnitude of this problem, current disease surveillance of wildlife populations across Europe is minimal. This initiative is designed to provide novel technologies which will contribute to the development of a comprehensive system of surveillance of wild animal diseases relevant to European public and animal health. Initiated by Dr Lea in the vet school, this project has allowed Dr Lea to expand his portfolio and apply his technological expertise into an area of international concern both within and outside the EU. In support of this work, Dr Lea and colleagues in the vet school have had considerable success in raising further funds from the EU totalling 6 million euros. The focus of the grant is to develop nucleic acid arrays for the detection of multiple pathogens in a single sample and serological arrays for investigating host response to the pathogen. A state of the art disease management system and epidemiological modelling systems are also being developed as part of this consortium. There are 13 partners across Europe and a network of 24 Associate Partners (wildlife specialists) involved in this crucially important program

Recent Publications

Past Research

Dr Lea's research career began with his PhD studies on immuno-endocrine aspects of implantation in the horse. Specifically he was interested in the formation of the endometrial cups and the maternal immunological response to these placental derived structures unique to equids. At McMaster University Dr Lea worked on the immunological basis of recurrent pregnancy failure in the human and investigated immunological and endocrine mechanisms that control this process using various strains of mice and human tissues. Inspired by his enthusiastic supervisor Professor Clark, Dr Lea's efforts were soon recognised with a Prize for best clinical presentation from the Canadian Fertility and Andrology Society in 1989. This was followed by a number of papers in which Dr Lea made his mark in the field of Reproductive Immunology. After 3 years in Canada, Dr Lea returned to the UK where he completed 2 fellowships in Edinburgh. For the first 3 years Dr Lea worked on a rat model of diabetes associated embryopathy and demonstrated an effect of diabetes on the embryo prior to implantation. A successful MRC grant then enabled Dr Lea to move to the Centre for Reproductive Biology in Edinburgh to work on the effects of the anti-gestogen (RU-486) on intra-uterine immune cells and cytokines in the human.

At the Rowett Research Institute, Dr Lea expanded his research interests further through investigation of the effects of nutrition on maternal immune and endocrine mechanisms important for reproductive function. This included the investigation of (1) nutrient deficiencies using rodent models, (2) mechanisms underlying the process of placental growth restriction in a sheep model of adolescent pregnancy and (3) the effects of diet, superovulation regimes and oocyte/embryo culture on DNA methylation and gene expression.

Nutritional effects on immune and endocrine processes in early pregnancy.

Nutrient deficiencies using rodent models

The immunomodulatory effects of pregnancy on the maternal immune system are well documented as are the effects of nutrition on immunity (e.g., trace elements, vitamins, polyunsaturated fatty acids etc). Dr Lea combined these two areas in a programme of research designed to determine how altered diet affects immune mechanisms and pathways central to reproductive success. Initially this was largely based on the normal maternal immune response to the allogeneic feto-placental unit and how this may be modified by maternal nutrition. To investigate this novel area Dr Lea began by using rat models of altered maternal nutrition and demonstrated changes in immune signalling molecules (cytokines) in response to maternal dietary changes in vitamin A and iron.

Placental growth restriction in a sheep model of adolescent pregnancy

Dr Lea worked on a sheep model of adolescent pregnancy where young growing pregnant ewes are fed twice x maintenance diet. In this model, the ewes get larger but the lambs are born small and are in need of post-natal care. Thus the partitioning of nutrients in favour of the growing mother effectively results in fetal under-nutrition and subsequent intra-uterine growth restriction. Reduced lamb size is associated with a restriction in placental growth and both placental and maternal hormone levels are altered. Dr Lea set out to determine the biological basis of this phenomenon and subsequently published data showing changes in both developmental and steroidogenic genes.

The effects of methionine deficiency on the oocyte and pre-implantation embryo in terms of DNA methylation and its developmental consequences for the foetus, neonate and adult.

In collaboration with Professors Sinclair and Young (University of, Nottingham) and Dr Rees (Rowett Research Institute, Aberdeen) Dr Lea has been investigating the physiological programming effects of this narrow window of altered methionine availability on pre and post-natal development using both sheep and rat models. Dr Lea's contribution to this programme was based on the possible programming effects on placental growth and function. This research was supported by the NIH with funds awarded to Sinclair, Rees, Lea and Young.

In 2004 Dr Lea received the prestigious 'J Christian Herr award for excellence in Reproductive Immunology research' from The American Society for Reproductive Immunology. Dr Lea maintains his passion for this area of research and currently Chairs the Reproductive Immunogy Group (RIG), satellite group of the British Society for Reproductive Immunology.

Whilst at the Rowett Research Institute, Dr Lea also established a program investigating the effects of chemicals in the environment which behave like reproductive hormones and potentially affect development of the fetus.

School of Veterinary Medicine and Science

University of Nottingham
Sutton Bonington Campus
Leicestershire, LE12 5RD

telephone: +44 (0)115 951 6116
fax: +44 (0)115 951 6415
email: veterinary-enquiries@nottingham.ac.uk