School of Biosciences
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Kevin Sinclair

Professor of Developmental Biology, Faculty of Science

Contact

  • workRoom 210 South Laboratory
    Sutton Bonington Campus
    Sutton Bonington
    Leicestershire
    LE12 5RD
    UK
  • work0115 951 6053
  • fax0115 951 6099

Biography

Ongoing research is addressing the hypothesis that maternal nutritional effects in developing oocytes and embryos, and procedures used in assisted reproduction, can program fetal development and adult health via heritable epigenetic changes to DNA methylation at specific gene loci in the oocyte and pre-implantation embryo. First to discover that developmental anomalies following mammalian embryo culture were due to errors in genomic imprinting (Nature Genetics, 27: 153-154). Similar phenomena have since been reported in human IVF pregnancies. Work supported by the National Institutes of Health (USA) demonstrated that reductions in folate and vitamin B12 in the diets of intending mothers (rat and sheep) lead to epigenetic modifications to DNA methylation and adult offspring with increased body fat and blood pressure, altered immune function and insulin resistance (showcased to the NICHD Advisory Council in Washington DC in January 2007; PNAS, 104: 19351-19356).

Provided the first detailed report of cardio-metabolic and musculo-skeletal health in aged cloned (by somatic-cell nuclear transfer (SCNT)) offspring (Nature Communications 7: 12359; Scientific Reports 7: 15685) and, most recently, provided details of concordant DNA methylation in embryonic and somatic-cell lineages (PLOS Genetics. 13: e1007060). Ongoing work is determining if the nature extent of (a) mtDNA heteroplasmy and (b) DNA methylation in different cell types can explain observed differences in metabolic and musculoskeletal health within and between cloned animals

Additional EU-FP7 - sponsored studies in sheep and mice assessed the effects of exposure to real-life levels of environmental chemicals on development of the fetal hypothalamic-pituitary-gonadal axis. Studies in sheep were initially based on animals grazing sewage-sludge treated pastures at various intervals during pregnancy (Scientific Reports. 6: 22279). From these studies specific groups of chemicals (e.g. phthalates and PCBs) were identified as being particularly harmful and have since been studied in separate studies. Exposure to these chemicals has a profound effect on testis development, with more subtle effects observed in the fetal ovary. Molecular studies are assessing global changes in gene and protein expression associated with such effects.

Current BBSRC funded studies are investigating the genetics of one-carbon metabolism in sheep in relation to productivity, fertility and health. Also, seeking to generate generate cytogenetically 'normal' and developmentally competent bovine and porcine sexed-embryos that have undergone genomic evaluations in order to promote the production of livestock that are genetically superior for a number of health and production-related traits.

Research Summary

Ongoing research is addressing the hypothesis that maternal nutritional effects in developing oocytes and embryos, and procedures used in assisted reproduction, can program fetal development and… read more

Selected Publications

Current Research

Ongoing research is addressing the hypothesis that maternal nutritional effects in developing oocytes and embryos, and procedures used in assisted reproduction, can program fetal development and adult health via heritable epigenetic changes to DNA methylation at specific gene loci in the oocyte and pre-implantation embryo. First to discover that developmental anomalies following mammalian embryo culture were due to errors in genomic imprinting (Nature Genetics, 27: 153-154). Similar phenomena have since been reported in human IVF pregnancies. Work supported by the National Institutes of Health (USA) demonstrated that reductions in folate and vitamin B12 in the diets of intending mothers (rat and sheep) lead to epigenetic modifications to DNA methylation and adult offspring with increased body fat and blood pressure, altered immune function and insulin resistance (showcased to the NICHD Advisory Council in Washington DC in January 2007; PNAS, 104: 19351-19356).

Provided the first detailed report of cardio-metabolic and musculo-skeletal health in aged cloned (by somatic-cell nuclear transfer (SCNT)) offspring (Nature Communications 7: 12359; Scientific Reports 7: 15685) and, most recently, provided details of concordant DNA methylation in embryonic and somatic-cell lineages (PLOS Genetics. 13: e1007060). Ongoing work is determining if the nature extent of (a) mtDNA heteroplasmy and (b) DNA methylation in different cell types can explain observed differences in metabolic and musculoskeletal health within and between cloned animals

Additional EU-FP7 - sponsored studies in sheep and mice assessed the effects of exposure to real-life levels of environmental chemicals on development of the fetal hypothalamic-pituitary-gonadal axis. Studies in sheep were initially based on animals grazing sewage-sludge treated pastures at various intervals during pregnancy (Scientific Reports. 6: 22279). From these studies specific groups of chemicals (e.g. phthalates and PCBs) were identified as being particularly harmful and have since been studied in separate studies. Exposure to these chemicals has a profound effect on testis development, with more subtle effects observed in the fetal ovary. Molecular studies are assessing global changes in gene and protein expression associated with such effects.

Current BBSRC funded studies are investigating the genetics of one-carbon metabolism in sheep in relation to productivity, fertility and health. Also, seeking to generate generate cytogenetically 'normal' and developmentally competent bovine and porcine sexed-embryos that have undergone genomic evaluations in order to promote the production of livestock that are genetically superior for a number of health and production-related traits.

School of Biosciences

University of Nottingham
Sutton Bonington Campus
Nr Loughborough
LE12 5RD, UK

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