Kevin Sinclair

Contact

• workRoom 210 South Laboratory
  Sutton Bonington Campus
  Sutton Bonington
  Leicestershire
  LE12 5RD
  UK
• work0115 951 6053
• fax0115 951 6099
• kevin.sinclair@nottingham.ac.uk

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

• YOUNG, L.E., FERNANDES, K., MCEVOY, T.G., BUTTERWITH, S.C., GUTIERREZ, C.G., CAROLAN, C., BROADBENT, P.J., ROBINSON, J.J., WILMUT, I. and SINCLAIR, K.D., 2001. Epigenetic change in IGF2R is associated with fetal overgrowth after sheep embryo culture Nature Genetics. 27(2), 153-154
• SINCLAIR, KEVIN D, ALLEGRUCCI, CINZIA, SINGH, RAVINDER, GARDNER, DAVID S, SEBASTIAN, SONIA, BISPHAM, JAYSON, THURSTON, ALEXANDRA, HUNTLEY, JOHN F, REES, WILLIAM D, MALONEY, CHRISTOPHER A and LEA, RICHARD, 2007. DNA methylation, insulin resistance, and blood pressure in offspring determined by maternal periconceptional B vitamin and methionine status. Proceedings of the National Academy of Sciences of the United States of America. 104(49), 19351-6
• ARMSTRONG, D.G., MCEVOY, T.G., BAXTER, G., ROBINSON, J.J., HOGG, C.O., WOAD, K.J., WEBB, R. and SINCLAIR, K.D., 2001. Effect of dietary energy and protein on bovine follicular dynamics and embryo production in vitro : associations with the ovarian insulin-like growth factor system Biology of Reproduction. 64(6), 1624-1632
• ADAMIAK, S.J., POWELL, K., ROOKE, J.A., WEBB, R. and SINCLAIR, K.D., 2006. Body composition, dietary carbohydrates and fatty acids determine post-fertilisation development of bovine oocytes in vitro. Reproduction. 131(2), 247-58

• View all 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.

• ZEEBAREE BK, KWONG WY, MANN GE, GUTIERREZ CG and SINCLAIR KD, 2018. Physiological responses of cultured bovine granulosa cells to elevated temperatures under low and high oxygen in the presence of different concentrations of melatonin. Theriogenology. 105, 107-114
• CLARE CE, BRASSINGTON AH, KWONG WY and SINCLAIR KD, 2018. One-Carbon Metabolism: Linking Nutritional Biochemistry to Epigenetic Programming of Long-Term Development. Annual review of animal biosciences. (In Press.)
• HUNTRISS J, BALEN AH, SINCLAIR KD, BRISON DR, PICTON HM and , 2018. Epigenetics and Reproductive Medicine: Scientific Impact Paper No. 57. BJOG : an international journal of obstetrics and gynaecology. 125(13), e43-e54
• WEERATHILAKE WADV, BRASSINGTON AH, WILLIAMS SJ, KWONG WY, SINCLAIR LA and SINCLAIR KD, 2018. Added dietary cobalt or vitamin B12, or injecting vitamin B12 does not improve performance or indicators of ketosis in pre- and post-partum Holstein-Friesian dairy cows. Animal : an international journal of animal bioscience. 1-10 (In Press.)
• KEVIN D SINCLAIR, 2018. When maternal periconceptional diet affects neurological development, it’s time to think Proceedings of the National Academy of Sciences of the United States of America.
• WATKINS AJ, DIAS I, TSURO H, ALLEN D, EMES RD, MORETON J, WILSON R, INGRAM RJM and SINCLAIR KD, 2018. Paternal diet programs offspring health through sperm- and seminal plasma-specific pathways in mice. Proceedings of the National Academy of Sciences of the United States of America. (In Press.)
• CORR SA, GARDNER DS, LANGLEY-HOBBS S, NESS MG, KITCHENER AC and SINCLAIR KD, 2017. Radiographic assessment of the skeletons of Dolly and other clones finds no abnormal osteoarthritis. Scientific reports. 7(1), 15685
• CHOI M, GENEREUX DP, GOODSON J, AL-AZZAWI H, ALLAIN SQ, SIMON N, PALASEK S, WARE CB, CAVANAUGH C, MILLER DG, JOHNSON WC, SINCLAIR KD, STÖGER R and LAIRD CD, 2017. Epigenetic memory via concordant DNA methylation is inversely correlated to developmental potential of mammalian cells. PLoS genetics. 13(11), e1007060
• SINCLAIR, KEVIN, RUTHERFORD, KENNETH, WALLACE, JACQUELINE, BRAMELD, JOHN, STÖGER, REINHARD, ALBERIO, RAMIRO, SWEETMAN, DYLAN, GARDNER, DAVID, PERRY, VIV, ADAM, CLARE and OTHERS, 2016. Epigenetics and developmental programming of welfare and production traits in farm animals Reproduction, Fertility and Development.
• SINCLAIR KD, CORR SA, GUTIERREZ CG, FISHER PA, LEE JH, RATHBONE AJ, CHOI I, CAMPBELL KH and GARDNER DS, 2016. Healthy ageing of cloned sheep. Nature communications. 7, 12359
• SINCLAIR, KD, RUTHERFORD, KMD, WALLACE, JM, BRAMELD, JM and ET AL., 2016. Epigenetics and developmental programming of welfare and production traits in farm animals. Reproduction, fertility, and development. 28(10), 1443-1478
• FOWLER PA, DRAKE AJ, O'SHAUGHNESSY PJ, BHATTACHARYA S, RAAB A, SINCLAIR KD, FELDMANN J and MEHARG AA, 2016. Comment on "Effects of Arsenite during Fetal Development on Energy Metabolism and Susceptibility to Diet-Induced Fatty Liver Diseases in Male Mice" and "Mechanisms Underlying Latent Disease Risk Associated with Early-Life Arsenic Exposure: Current Trends and Scientific Gaps". Environmental health perspectives. 124(6), A99
• GREGSON E, WEBB R, SHELDRICK EL, CAMPBELL BK, MANN GE, LIDDELL S and SINCLAIR KD, 2016. Molecular determinants of a competent bovine corpus luteum: first- vs final-wave dominant follicles. Reproduction (Cambridge, England). 151(6), 563-75
• LEA RG, AMEZAGA MR, LOUP B, MANDON-PÉPIN B, STEFANSDOTTIR A, FILIS P, KYLE C, ZHANG Z, ALLEN C, PURDIE L, JOUNEAU L, COTINOT C, RHIND SM, SINCLAIR KD and FOWLER PA, 2016. The fetal ovary exhibits temporal sensitivity to a 'real-life' mixture of environmental chemicals. Scientific reports. 6, 22279
• XU J and SINCLAIR KD, 2015. One-carbon metabolism and epigenetic regulation of embryo development. Reproduction, fertility, and development. 27(4), 667-76
• DRAKE AJ, O'SHAUGHNESSY PJ, BHATTACHARYA S, MONTEIRO A, KERRIGAN D, GOETZ S, RAAB A, RHIND SM, SINCLAIR KD, MEHARG AA, FELDMANN J and FOWLER PA, 2015. In utero exposure to cigarette chemicals induces sex-specific disruption of one-carbon metabolism and DNA methylation in the human fetal liver. BMC medicine. 13, 18
• SCHAEDLICH K, SCHMIDT JS, KWONG WY, SINCLAIR KD, KURZ R, JAHNKE HG and FISCHER B, 2014. Impact of di-ethylhexylphthalate exposure on metabolic programming in P19 ECC-derived cardiomyocytes. Journal of applied toxicology : JAT. 35(7), 861-9
• DUNFORD LJ, SINCLAIR KD, KWONG WY, STURROCK C, CLIFFORD BL, GILES TC and GARDNER DS, 2014. Maternal protein-energy malnutrition during early pregnancy in sheep impacts the fetal ornithine cycle to reduce fetal kidney microvascular development. FASEB journal : official publication of the Federation of American Societies for Experimental Biology. 28(11), 4880-92
• ALBERIO R and SINCLAIR KD, 2014. Can we make a placenta in the Petri dish? Reproduction (Cambridge, England). 147(5), E3
• WATKINS AJ and SINCLAIR KD, 2014. Paternal low protein diet affects adult offspring cardiovascular and metabolic function in mice. American journal of physiology. Heart and circulatory physiology. 306(10), H1444-52
• DUNFORD, LOUISE J., SINCLAIR, KEVIN D., KWONG, WING Y., STURROCK, CRAIG, CLIFFORD, BETHAN L., GILES, TOM C. and GARDNER, DAVID S., 2014. Maternal protein-energy malnutrition during early pregnancy in sheep impacts the fetal ornithine cycle to reduce fetal kidney microvascular development: Faseb Journal Faseb Journal. 28(11), 4880-4892
• SINCLAIR KD and WATKINS AJ, 2013. Parental diet, pregnancy outcomes and offspring health: metabolic determinants in developing oocytes and embryos. Reproduction, fertility, and development. 26(1), 99-114
• STEEGERS-THEUNISSEN RP, TWIGT J, PESTINGER V and SINCLAIR KD, 2013. The periconceptional period, reproduction and long-term health of offspring: the importance of one-carbon metabolism. Human reproduction update. 19(6), 640-55
• SINCLAIR KD, GARNSWORTHY PC, MANN GE and SINCLAIR LA, 2013. Reducing dietary protein in dairy cow diets: implications for nitrogen utilization, milk production, welfare and fertility. Animal : an international journal of animal bioscience. 8(2), 262-74
• JOSEPH, C., HUNTER, M.G., SINCLAIR, K.D. and ROBINSON, R.S., 2012. The expression, regulation and function of secreted protein, acidic, cysteine-rich (sparc) in the follicle-luteal transition Reproduction. 144(3), 361-372
• BELLINGHAM M, FIANDANESE N, BYERS A, COTINOT C, EVANS NP, POCAR P, AMEZAGA MR, LEA RG, SINCLAIR KD, RHIND SM and FOWLER PA, 2012. Effects of exposure to environmental chemicals during pregnancy on the development of the male and female reproductive axes. Reproduction in domestic animals = zuchthygiene. 47 Suppl 4, 15-22
• PRING SR, OWEN M, KING JR, SINCLAIR KD, WEBB R, FLINT APF and GARNSWORTHY PC, 2012. A mathematical model of the bovine oestrous cycle: simulating outcomes of dietary and pharmacological interventions. Journal of theoretical biology. 313, 115-26
• MALONEY CA, HAY SM, REID MD, DUNCAN G, NICOL F, SINCLAIR KD and REES WD, 2012. A methyl-deficient diet fed to rats during the pre- and peri-conception periods of development modifies the hepatic proteome in the adult offspring. Genes & nutrition. (In Press.)
• MALONEY, CHRISTOPHER A, HAY, SUSAN M, YOUNG, LORAINE E, SINCLAIR, KEVIN D and REES, WILLIAM D, 2011. A methyl-deficient diet fed to rat dams during the peri-conception period programs glucose homeostasis in adult male but not female offspring. The Journal of nutrition. 141(1), 95-100
• MALONEY, CA, HAY, SM, YOUNG, LE, SINCLAIR, KD and REES, WD, 2011. A Methyl-Deficient Diet Fed To Rat Dams During The Peri-Conception Period Programs Glucose Homeostasis In Adult Male But Not Female Offspring Journal Of Nutrition. 141(1), 95-100
• HUGHES, J., KWONG, W.Y., LI, D., SALTER, A.M., LEA, R.G. and SINCLAIR, K.D., 2011. Effects of omega-3 and -6 polyunsaturated fatty acids on ovine follicular cell steroidogenesis, embryo development and molecular markers of fatty acid metabolism Reproduction: The Journal of the Society for Reproduction and Fertility. 141(1), 105-118
• TWIGT, J.M., HAMMICHE, F., SINCLAIR, K.D., BECKERS, N.G., VISSER, J.A., LINDEMANS, J., DE JONG, F.H., LAVEN, J.S.E. and STEEGERS-THEUNISSEN, R.P., 2011. Preconception folic acid use modulates estradiol and follicular responses to ovarian stimulation. JCEM: The Journal of Clinical Endocrinology and Metabolism. 96(2), E322-329
• FOWLER PA, BELLINGHAM M, SINCLAIR KD, EVANS NP, POCAR P, FISCHER B, SCHAEDLICH K, SCHMIDT J, AMEZAGA MR, BHATTACHARYA S, RHIND SM and O'SHAUGHNESSY PJ, 2011. Impact Of Endocrine-Disrupting Compounds (Edcs) On Female Reproductive Health. Molecular And Cellular Endocrinology. (In Press.)
• SINCLAIR KD, KARAMITRI A and GARDNER DS, 2010. Dietary Regulation Of Developmental Programming In Ruminants: Epigenetic Modifications In The Germline. Society Of Reproduction And Fertility Supplement. 67, 59-72
• KWONG, W.Y., ADAMIAK, S.J., GWYNN, A., SINGH, R. and SINCLAIR, K.D., 2010. Endogenous folates and single-carbon metabolism in the ovarian follicle, oocyte and pre-implantation embryo Reproduction: The Journal of the Society for Reproduction and Fertility. 139(4), 705-15
• RHIND SM, EVANS NP, BELLINGHAM M, SHARPE RM, COTINOT C, MANDON-PEPIN B, LOUP B, SINCLAIR KD, LEA RG, POCAR P, FISCHER B, VAN DER ZALM E, HART K, SCHMIDT J, AMEZAGA MR and FOWLER PA, 2010. Effects Of Environmental Pollutants On The Reproduction And Welfare Of Ruminants. Animal : An International Journal Of Animal Bioscience. 4(7), 1227-1239
• WONNACOTT, K.E., KWONG, W.Y., HUGHES, J., SALTER, A.M., LEA, R.G., GARNSWORTHY, P.C. and SINCLAIR, K.D., 2010. Dietary omega-3 and-6 polyunsaturated fatty acids affect the composition and development of sheep granulosa cells, oocytes and embryos Reproduction. 139(1), 57-69
• GARDNER, D S, OZANNE, S E and SINCLAIR, K D, 2009. Effect of the early-life nutritional environment on fecundity and fertility of mammals. Philosophical transactions of the Royal Society of London. Series B, Biological sciences. 364(1534), 3419-27
• GRACE KS and SINCLAIR KD, 2009. Assisted Reproductive Technology, Epigenetics, And Long-Term Health: A Developmental Time Bomb Still Ticking. Seminars In Reproductive Medicine. 27(5), 409-16
• FOULADI-NASHTA AA, WONNACOTT KE, GUTIERREZ CG, GONG JG, SINCLAIR KD, GARNSWORTHY PC and WEBB R, 2009. Oocyte Quality In Lactating Dairy Cows Fed On High Levels Of N-3 And N-6 Fatty Acids. Reproduction (Cambridge, England). 138(5), 771-81
• ROOKE JA, AINSLIE A, WATT RG, ALINK FM, MCEVOY TG, SINCLAIR KD, GARNSWORTHY PC and WEBB R, 2009. Dietary Carbohydrates And Amino Acids Influence Oocyte Quality In Dairy Heifers. Reproduction, Fertility, And Development. 21(3), 419-27
• KANAKKAPARAMBIL, R., SINGH, R., LI, D., WEBB, R. and SINCLAIR, K.D., 2009. B-vitamin and homocysteine status determines ovarian response to Gonadotropin treatment in sheep. Biology of Reproduction. 80(4), 743-752
• WONNACOTT KE, KWONG WY, HUGHES J, SALTER AM, LEA RG, GARNSWORTHY PC and SINCLAIR KD, 2009. Dietary omega-3 and -6 polyunsaturated fatty acids affect the composition and development of sheep granulosa cells, oocytes and embryos. Reproduction (Cambridge, England). 139(1), 57-69
• GARNSWORTHY PC, FOULADI-NASHTA AA, MANN GE, SINCLAIR KD and WEBB R, 2009. Effect of dietary-induced changes in plasma insulin concentrations during the early post partum period on pregnancy rate in dairy cows. Reproduction (Cambridge, England). 137(4), 759-68
• GARNSWORTHY, P.C., FOULADI-NASHTA, A.A., MANN, G.E., SINCLAIR, K.D. and WEBB, R., 2009. Effect of dietary-induced changes in plasma insulin concentrations during the early post partum period on pregnancy rate in dairy cows Reproduction. 137(4), 759-768
• THURSTON, A., TAYLOR, J., GARDNER, J., SINCLAIR, K.D. and YOUNG, L.E., 2008. Monoallelic expression of nine imprinted genes in the sheep embryo occurs after the blastocyst stage Reproduction. 135(1), 29-40
• GARNSWORTHY PC, GONG JG, ARMSTRONG DG, NEWBOLD JR, MARSDEN M, RICHARDS SE, MANN GE, SINCLAIR KD and WEBB R, 2008. Nutrition, Metabolism, And Fertility In Dairy Cows: 3. Amino Acids And Ovarian Function. Journal Of Dairy Science. 91(11), 4190-7
• SINCLAIR KD, LUNN LA, KWONG WY, WONNACOTT K, LINFORTH RST and CRAIGON J, 2008. Amino acid and fatty acid composition of follicular fluid as predictors of in-vitro embryo development. Reproductive biomedicine online. 16(6), 859-68
• GARNSWORTHY PC, LOCK A, MANN GE, SINCLAIR KD and WEBB R, 2008. Nutrition, metabolism, and fertility in dairy cows: 2. Dietary fatty acids and ovarian function. Journal of dairy science. 91(10), 3824-33
• GARNSWORTHY PC, LOCK A, MANN GE, SINCLAIR KD and WEBB R, 2008. Nutrition, metabolism, and fertility in dairy cows: 1. Dietary energy source and ovarian function. Journal of dairy science. 91(10), 3814-23
• ROOKE JA, AINSLIE A, WATT RG, ALINK FM, MCEVOY TG, SINCLAIR KD, GARNSWORTHY PC and WEBB R, 2008. Feeding frequency has diet-dependent effects on plasma hormone concentrations but does not affect oocyte quality in dairy heifers fed fibre- or starch-based diets. Animal : an international journal of animal bioscience. 2(9), 1361-70
• GARNSWORTHY PC, SINCLAIR KD and WEBB R, 2008. Integration of physiological mechanisms that influence fertility in dairy cows. Animal : an international journal of animal bioscience. 2(8), 1144-52
• GARDNER DS, LEA RG and SINCLAIR KD, 2008. Developmental programming of reproduction and fertility: what is the evidence? Animal : an international journal of animal bioscience. 2(8), 1128-34
• GARNSWORTHY, P.C., SINCLAIR, K.D. and WEBB, R., 2008. Integration of physiological mechanisms that influence fertility in dairy cows Animal. 2(8), 1144-1152
• SINCLAIR, K.D., LUNN, L.A., KWONG, W.Y., WONNACOTT, K., LINFORTH, R.S.T. and CRAIGON, J., 2008. Amino acid and fatty acid composition of follicular fluid as predictors of in-vitro embryo development Reproductive Biomedicine Online. 16(6), 859-868
• ROOKE, JA, AINSLIE, A, WATT, RG, ALINK, FM, MCEVOY, TG, SINCLAIR, KD, GARNSWORTHY, PC and WEBB, R, 2008. Feeding Frequency Has Diet-Dependent Effects On Plasma Hormone Concentrations But Does Not Affect Oocyte Quality In Dairy Heifers Fed Fibre- Or Starch-Based Diets Animal. 2(9), 1361-1370
• GARNSWORTHY, P.C., LOCK, A., MANN, G.E., SINCLAIR, K.D. and WEBB, R, 2008. Nutrition, metabolism, and fertility in dairy cows: 2. Dietary fatty acids and ovarian function Journal of Dairy Science. 91(10), 3824-3833
• GARNSWORTHY, P.C., LOCK, A., MANN, G.E., SINCLAIR, K.D. and WEBB, R, 2008. Nutrition, metabolism, and fertility in dairy cows: 1. Dietary energy source and ovarian function Journal of Dairy Science. 91(10), 3814-3823
• GARDNER, D.S., LEA R.G. and SINCLAIR, K.S., 2008. Developmental programming of reproduction and fertility: What is the evidence? Animal. 2, 1128-1134
• SINCLAIR, KEVIN D, 2008. Assisted reproductive technologies and pregnancy outcomes: mechanistic insights from animal studies. Seminars in reproductive medicine. 26(2), 153-61
• GARDNER, D.S., LEA R.G. and SINCLAIR, K.S., 2008. Developmental programming of reproduction and fertility: What is the evidence? Animal. 2, 1128-1134
• SINCLAIR, KEVIN D, ALLEGRUCCI, CINZIA, SINGH, RAVINDER, GARDNER, DAVID S, SEBASTIAN, SONIA, BISPHAM, JAYSON, THURSTON, ALEXANDRA, HUNTLEY, JOHN F, REES, WILLIAM D, MALONEY, CHRISTOPHER A and LEA, RICHARD, 2007. DNA methylation, insulin resistance, and blood pressure in offspring determined by maternal periconceptional B vitamin and methionine status. Proceedings of the National Academy of Sciences of the United States of America. 104(49), 19351-6
• ROOKE, JA, MCEVOY, TG, ASHWORTH,CJ, ROBINSON,JJ, WILMUT,I, YOUNG,LE and SINCLAIR,KD, 2007. Ovine fetal development is more sensitive to perturbation by the presence of serum in embryo culture before rather than after compaction. Theriogenology. 67(3), 639-647
• SINCLAIR, K D, LEA, R G, REES, W D and YOUNG, L E, 2007. The developmental origins of health and disease: current theories and epigenetic mechanisms. Society of Reproduction and Fertility supplement. 64, 425-43
• SINGH, R and SINCLAIR, K D, 2007. Metabolomics: approaches to assessing oocyte and embryo quality. Theriogenology. 68 Suppl 1, S56-62
• SINCLAIR, KEVIN D and SINGH, RAVINDER, 2007. Modelling the developmental origins of health and disease in the early embryo. Theriogenology. 67(1), 43-53
• SINCLAIR,K.D, LEA,R.G, REES,W.D and YOUNG,L.E, 2007. The developmental origins of health and disease; current theories and epigenetic mechanisms Society for Reproduction and Fertility Supplement. 64, 425-443
• POWELL, K, ROOKE, J A, MCEVOY, T G, ASHWORTH, C J, ROBINSON, J J, WILMUT, I, YOUNG, L E and SINCLAIR, K D, 2006. Zygote donor nitrogen metabolism and in vitro embryo culture perturbs in utero development and IGF2R expression in ovine fetal tissues. Theriogenology. 66(8), 1901-12
• ADAMIAK, S.J., POWELL, K., ROOKE, J.A., WEBB, R. and SINCLAIR, K.D., 2006. Body composition, dietary carbohydrates and fatty acids determine post-fertilisation development of bovine oocytes in vitro. Reproduction. 131(2), 247-58
• SINGH, R, FOULADI-NASHTA, A A, LI, D, HALLIDAY, N, BARRETT, D A and SINCLAIR, K D, 2006. Methotrexate induced differentiation in colon cancer cells is primarily due to purine deprivation. Journal of cellular biochemistry. 99(1), 146-55
• STEELE, W, ALLEGRUCCI, C, SINGH, R, LUCAS, E, PRIDDLE, H, DENNING, C, SINCLAIR, K and YOUNG, L, 2005. Human embryonic stem cell methyl cycle enzyme expression: modelling epigenetic programming in assisted reproduction? Reproductive Biomedicine online. 10(6), 755-66
• ALLEGRUCCI, C., DENNING, C.N., BURRIDGE, P., STEELE, W., SINCLAIR, K.D. and YOUNG, L.E., 2005. Human embryonic stem cells as a model for nutritional programming: an evaluation Reproductive Toxicology. 20(3), 353-367
• ALLEGRUCCI C, DENNING CN, BURRIDGE P, STEELE W, SINCLAIR KD and YOUNG LE, 2005. Human embryonic stem cells as a model for nutritional programming: an evaluation. Reproductive toxicology (Elmsford, N.Y.). 20(3), 353-67
• ADAMIAK, S.J., MACKIE, K., WATT, R.G., WEBB, R. and SINCLAIR, K.D., 2005. Impact of nutrition on oocyte quality: cumulative effects of body composition and diet leading to hyperinsulinemia in cattle. Biology of Reproduction. 73(5), 918-926
• QUINTANS, G, VIÑOLES, C and SINCLAIR, K D, 2004. Follicular growth and ovulation in postpartum beef cows following calf removal and GnRH treatment. Animal Reproduction Science. 80(1-2), 5-14
• ROOKE, J A, EWEN, M, MACKIE, K, STAINES, M E, MCEVOY, T G and SINCLAIR, K D, 2004. Effect of ammonium chloride on the growth and metabolism of bovine ovarian granulosa cells and the development of ovine oocytes matured in the presence of bovine granulosa cells previously exposed to ammonium chloride. Animal Reproduction Science. 84(1-2), 53-71
• QUINTANS, G., VINOLES, C. and SINCLAIR, K. D., 2004. Follicular growth and ovulation in postpartum beef cows following calf removal and GnRH treatment Animal Reproduction Science. VOL 80(NUMBER 1-2), 5-14
• YOUNG,L.E., REES,W.D. and SINCLAIR,K.D, 2004. Programming in the pre-implantation embryo. In: Fetal nutrition and Adult Disease: Programming of chronic disease through fetal exposure to undernutrition CAB International, Oxford.
• SINCLAIR KD, ROOKE JA and MCEVOY TG, 2003. Regulation of nutrient uptake and metabolism in pre-elongation ruminant embryos. Reproduction (Cambridge, England) Supplement. 61, 371-85
• MCEVOY TG, ASHWORTH CJ, ROOKE JA and SINCLAIR KD, 2003. Consequences of manipulating gametes and embryos of ruminant species. Reproduction (Cambridge, England) Supplement. 61, 167-82
• SINCLAIR, K. D., ROOKE, J. A. and MCEVOY, T. G., 2003. Regulation of nutrient uptake and metabolism in pre-elongation ruminant embryos Reproduction. Supplement. ISSU 61, 371-385
• MCEVOY, T. G., ASHWORTH, C. J., ROOKE, J. A. and SINCLAIR, K. D., 2003. Consequences of manipulating gametes and embryos of ruminant species Reproduction. Supplement. ISSU 61, 167-182
• SINCLAIR, K.D., GARNSWORTHY, P.C. and WEBB, R., 2003. Recent advances in reproductive technologies : implications for livestock production and animal nutrition. In: GARNSWORTHY, P.C. and WISEMAN, J., eds., Recent Advances in Animal Nutrition - 2003 Nottingham University Press. 89-113
• MANN GE, GREEN MP, SINCLAIR KD, DEMMERS KJ, FRAY MD, GUTIERREZ CG, GARNSWORTHY PC and WEBB R, 2003. Effects of circulating progesterone and insulin on early embryo development in beef heifers. Animal reproduction science. 79(1-2), 71-9
• MANN, G.E., GREEN, M.P., SINCLAIR, K.D., DEMMERS, K.J., FRAY, M.D., GUTIERREZ, C.G., GARNSWORTHY, P.C. and WEBB, R., 2003. Effects of circulating progesterone and insulin on early embryo development in beef heifers Animal Reproduction Science. VOL 79(NUMBER 1-2), 71-79
• SINCLAIR, K. D., MOLLE, G., REVILLA, R., ROCHE, J. F., QUINTANS, G., MARONGIU, L., SANZ, A., MACKEY, D. R. and DISKIN, M. G., 2002. Ovulation of the first dominant follicle arising after day 21 post partum in suckling beef cows Animal Science. VOL 75(PART 1), 115-126
• DAWUDA, P. M., SCAIFE, J. R., HUTCHINSON, J. S. and SINCLAIR, K. D., 2002. Mechanisms linking under-nutrition and ovarian function in beef heifers Animal Reproduction Science. VOL 74(NUMBER 1-2), 11-26
• PUSHPAKUMARA, P.G.A., ROBINSON, R.S., DEMMERS, K.J., MANN, G.E., SINCLAIR, K.D., WEBB, R. and WATHES, D.C., 2002. Expression of the insulin-like growth factor (IGF) system in the bovine oviduct at oestrus and during early pregnancy Reproduction. VOL 123(PART 6), 859-868
• PUSHPAKUMARA PG, ROBINSON RS, DEMMERS KJ, MANN GE, SINCLAIR KD, WEBB R and WATHES DC, 2002. Expression of the insulin-like growth factor (IGF) system in the bovine oviduct at oestrus and during early pregnancy. Reproduction (Cambridge, England). 123(6), 859-68
• DAWUDA PM, SCAIFE JR, HUTCHINSON JS and SINCLAIR KD, 2002. Mechanisms linking under-nutrition and ovarian function in beef heifers. Animal reproduction science. 74(1-2), 11-26
• ARMSTRONG, D.G., MCEVOY, T.G., BAXTER, G., ROBINSON, J.J., HOGG, C.O., WOAD, K.J., WEBB, R. and SINCLAIR, K.D., 2001. Effect of dietary energy and protein on bovine follicular dynamics and embryo production in vitro : associations with the ovarian insulin-like growth factor system Biology of Reproduction. 64(6), 1624-1632
• MALTIN,C.A., LOBLEY,G.E., GRANT,G.M., MILLER,L.A., KYLE,D.G., HORGAN,G.W., MATTHEWS,K.R. and SINCLAIR,K.D., 2001. Factors influencing beef eating quality. II. Effect of nutritional regimen and genotype on muscle fibre characteristics Animal Science. 72, 279
• MCEVOY, T G, ROBINSON, J J and SINCLAIR, K D, 2001. Developmental consequences of embryo and cell manipulation in mice and farm animals. Reproduction. 122(4), 507-18
• SINCLAIR, K. D., LOBLEY, G. E., HORGAN, G. W., KYLE, D. J., PORTER, A. D., MATTHEWS, K. R., WARKUP, C. C. and MALTIN, C. A., 2001. Factors influencing beef eating quality. 1. Effects of nutritional regimen and genotype on organoleptic properties and instrumental texture Animal Science. VOL 72(PART 2), 269-278
• MCEVOY, T., ROBINSON, J. J., ASHWORTH, C. J., ROOKE, J. A. and SINCLAIR, K. D., 2001. FEED AND FORAGE TOXICANTS AFFECTING EMBRYO SURVIVAL AND FETAL DEVELOPMENT Theriogenology. VOL 55(NO 1), 113-130
• MALTIN, C A, DELDAY, M I, SINCLAIR, K D, STEVEN, J and SNEDDON, A A, 2001. Impact of manipulations of myogenesis in utero on the performance of adult skeletal muscle. Reproduction. 122(3), 359-74
• ARMSTRONG, D G, MCEVOY, T G, BAXTER, G, ROBINSON, J J, HOGG, C O, WOAD, K J, WEBB, R and SINCLAIR, K D, 2001. Effect of dietary energy and protein on bovine follicular dynamics and embryo production in vitro: associations with the ovarian insulin-like growth factor system. Biology of Reproduction. 64(6), 1624-32
• YOUNG, L.E., FERNANDES, K., MCEVOY, T.G., BUTTERWITH, S.C., GUTIERREZ, C.G., CAROLAN, C., BROADBENT, P.J., ROBINSON, J.J., WILMUT, I. and SINCLAIR, K.D., 2001. Epigenetic change in IGF2R is associated with fetal overgrowth after sheep embryo culture Nature Genetics. 27(2), 153-154
• YOUNG LE, FERNANDES K, MCEVOY TG, BUTTERWITH SC, GUTIERREZ CG, CAROLAN C, BROADBENT PJ, ROBINSON JJ, WILMUT I and SINCLAIR KD, 2001. Epigenetic change in IGF2R is associated with fetal overgrowth after sheep embryo culture. Nature genetics. 27(2), 153-4
• MCEVOY TG, ROBINSON JJ, ASHWORTH CJ, ROOKE JA and SINCLAIR KD, 2001. Feed and forage toxicants affecting embryo survival and fetal development. Theriogenology. 55(1), 113-29
• SINCLAIR KD, YOUNG LE, WILMUT I and MCEVOY TG, 2001. In-utero overgrowth in ruminants following embryo culture: lessons from mice and a warning to men. Human reproduction (Oxford, England). 15 Suppl 5, 68-86
• SINCLAIR, K.D., KURAN, M., GEBBIE, F.E., WEBB, R. and MCEVOY, T.G., 2000. Nitrogen metabolism and fertility in cattle: II. Development of oocytes recovered from heifers offered diets differing in their rate of nitrogen release in the rumen Journal of Animal Science. VOL 78(PART 10), 2670-2680
• MCEVOY, T. G., SINCLAIR, K. D., YOUNG, L. E., WILMUT, I. and ROBINSON, J. J., 2000. Large offspring syndrome and other consequences of ruminant embryo culture in vitro: relevance to blastocyst culture in human ART Human Fertility. VOL 3(PART 4), 238-246
• SINCLAIR, K. D., YOUNG, L. E., WILMUT, I. and MCEVOY, T. G., 2000. In-utero overgrowth in ruminants following embryo culture: lessons from mice and a warning to men Human Reproduction. VOL 15(SUPP/5), 68-86
• SINCLAIR, K D, SINCLAIR, L A and ROBINSON, J J, 2000. Nitrogen metabolism and fertility in cattle: I. Adaptive changes in intake and metabolism to diets differing in their rate of energy and nitrogen release in the rumen. Journal of Animal Science. 78(10), 2659-69
• MCEVOY,, SINCLAIR,, YOUNG,, WILMUT, and ROBINSON,, 2000. Large offspring syndrome and other consequences of ruminant embryo culture in vitro: relevance to blastocyst culture in human ART. Human Fertility. 3(4), 238-246
• LOBLEY GE, SINCLAIR KD, GRANT CM, MILLER L, MANTLE D, CALDER AG, WARKUP CC and MALTIN CA, 2000. The effects of breed and level of nutrition on whole-body and muscle protein metabolism in pure-bred Aberdeen angus and Charolais beef steers. The British journal of nutrition. 84(3), 275-84
• SINCLAIR KD, KURAN M, GEBBIE FE, WEBB R and MCEVOY TG, 2000. Nitrogen metabolism and fertility in cattle: II. Development of oocytes recovered from heifers offered diets differing in their rate of nitrogen release in the rumen. Journal of animal science. 78(10), 2670-80
• SINCLAIR KD, MCEVOY TG, MAXFIELD EK, MALTIN CA, YOUNG LE, WILMUT I, BROADBENT PJ and ROBINSON JJ, 1999. Aberrant fetal growth and development after in vitro culture of sheep zygotes. Journal of reproduction and fertility. 116(1), 177-86
• MCEVOY TG, SINCLAIR KD, BROADBENT PJ, GOODHAND KL and ROBINSON JJ, 1999. Post-natal growth and development of Simmental calves derived from in vivo or in vitro embryos. Reproduction, fertility, and development. 10(6), 459-64
• ARMSTRONG, D.G., BAXTER, G., HOGG, C.O. and WOAD, K.J., 1998. The effect of different energy and protein diets on the expression of mRNA encoding components of the ovarian IGF-system in cattle Journal of Reproduction and Fertility. Abstract Series. ISSUE 22, 13
• SINCLAIR, K D, DUNNE, L D, MAXFIELD, E K, MALTIN, C A, YOUNG, L E, WILMUT, I, ROBINSON, J J and BROADBENT, P J, 1998. Fetal growth and development following temporary exposure of day 3 ovine embryos to an advanced uterine environment. Reproduction, Fertility and Development. 10(3), 263-9
• MAXFIELD EK, SINCLAIR KD, BROADBENT PJ, MCEVOY TG, ROBINSON JJ and MALTIN CA, 1998. Short-term culture of ovine embryos modifies fetal myogenesis. The American journal of physiology. 274(6 Pt 1), E1121-3
• MAXFIELD EK, SINCLAIR KD, DUNNE LD, BROADBENT PJ, ROBINSON JJ, STEWART E, KYLE DG and MALTIN CA, 1998. Temporary exposure of ovine embryos to an advanced uterine environment does not affect fetal weight but alters fetal muscle development. Biology of reproduction. 59(2), 321-5
• YOUNG LE, SINCLAIR KD and WILMUT I, 1998. Large offspring syndrome in cattle and sheep. Reviews of reproduction. 3(3), 155-63
• MCEVOY, T.G., SINCLAIR, K.D., STAINES, M.E., ROBINSON, J.J., ARMSTRONG, D. and WEBB, R., 1997. In vitro blastocyst production in relation to energy and protein intake prior to oocyte collection Journal of Reproduction and Fertility. Abstract Series. 19, 51
• ARMSTRONG, D.G., BAXTER, G., GUTIERREZ, C.G., WOAD, K.J., SINCLAIR, K.D., ROBINSON, J.J., MCEVOY, T.G. and WEBB, R., 1997. Ovarian IGF-II mRNA expression in cattle fed different energy and protein diets Journal of Reproduction and Fertility. Abstract Series. 19, 51
• SINCLAIR KD and BROADBENT PJ, 1996. Increasing the efficiency of suckled calf production using embryo transfer technology. The Veterinary record. 139(17), 409-12