Markers of ooctye quality in health and infertility
This long running programme of research is conducted through collaboration with the clinical team (Prof Adam Balen, Mr Anthony Rutherford and Mrs Vinay Sharma) at the Leeds Centre for Reproductive Medicine (LCRM); and Prof Bruce Campbell from the University of Nottingham, UK. The project has identified novel genes and investigated the clinical relevance of genetic and non-invasive metabolic markers of oocyte developmental competence (quality) in large animals and humans during health, age and infertility. The work has provided provides fundamental insights in human egg development and fertility.
Isolation and expression of the gametocyte-specific factor 1 gene (GTSF1) in human oocytes and preimplantation embryos
Collaboration with Professor Richard Anderson, MRC Human Reproductive Sciences Unit, University of Edinburgh, UK. Understanding the expression, localisation and function of human oocyte-specific genes is useful for determining their role in human reproduction. This collaboration represents the first experimental cloning of the human GTSF1 gene. The collaboration has pooled resources in Leeds and Edinburgh to assess GTSF1 expression in the human female germline from the fetal ovary through to mature oocytes in adults and beyond to preimplantation embryos. This study, together with our work in other large animal species indicates an important role for this gene in mammalian oogenesis.
Ovarian tissue cryopreservation for fertility preservation in humans
Studies of ovarian tissue cryopreservation for fertility preservation have been conducted in collaboration with Prof Bruce Campbell, University of Nottingham; Prof Bob Web, Scottish Agricultural Colleges, Edinburgh; and Dr Adam Glaser, St Jamess University Hospital, Leeds. This programme has investigated: (i) the biology of ovarian cortex cryopreservation with fertility restoration by autotransplantation or by the complete in vitro growth and maturation of follicles; and (ii) the efficiency of whole ovary freezing and transplantation for fertility preservation. This work has contributed to the development of strategies for fertility preservation in girls and young women with severe diseases such as cancer.
The biology of preimplantation embryo development in humans
This long running research programme is conducted in collaboration with Prof Adam Balen, Mr Anthony Rutherford and Mrs Vinay Sharma at the LCRM and Dr Kay Elder from Bourne Hall Clinic, Cambridge, UK. This research maps how embryo metabolism, genetics, epigenetics and genomic imprinting change during preimplantation embryo development following the use of assisted reproduction technologies in large animals and humans. This work has provided valuable insights into human embryo development.
Quantitative assessment of DNA methylation at imprinted loci in human preimplantation embryos
Collaboration with Dr Adele Murrell, Cancer Research UK Cambridge Institute, Cambridge, UK. The project established for the first time that pyrosequencing provides a robust method with which to determine the methylation status of genes in early human development, in which cell numbers are limiting. Specifically, the methylation status of thee imprinted gene differentially methylated regions (DMRs) were achieved in human blastocysts. The development is important since assisted reproduction and infertility are known to affect epigenetic programming in gametes and early embryos and the method developed here provides a way to assess normal epigenetic programming.
Marie Curie REPROTRAIN International Training Network
International consortium carrying out basic research into the cell biology, molecular biology and proteomics of sperm. The consortium has labs in the UK, Spain, France, Italy, Germany and the Netherlands containing 14 early stage (ESR) and experience (ER) researchers working on various, inter-related projects in Andrology and Urology.
HABSelect: Testing and investigating a new sperm selection method for improving ICSI live birth rates.
This is a UK wide consortium of 10 centres (Leeds, Sheffield, Birmingham, London, Liverpool, Manchester, Aberdeen, Dundee and Southampton) running a major clinical trial for efficacy of sperm selection by hyaluronan binding with a parallel laboratory based mechanistic evaluation of the novel selection process.
Key Funding Successes
The lifecycle and legacy of human oocytes in health, age and infertility.
Medical Research Council Grant
This new project will developed a detailed map of how the transcriptome and epigenome and metabolic machinery of human oocytes change throughout oogenesis in healthy women and will show how these parameters can be altered with advancing age and infertility.
Preservation of fertility in monovular species
Medical Research Council Grant
This project investigated the efficacy of whole ovary cryopreservation and autotransplantation as a means to preserve and restore female fertility in monovular species. The project used sheep ovaries as a model for whole ovary freezing in humans.
Biological foundation of epigenetic investigations of ART-derived human oocytes and preimplantation embryos
Medical Research Council Grant
This project has characterised the expression of key imprinted genes and epigenetic events in human oocytes and across human preimplantation embryo development and has established for the first time that pyrosequencing provides a robust method with which to determine the methylation status of genes in early human development.
Molecular and genetic aspects of male infertility and reproductive function.
FP7 Marie Curie Grant
Two projects in cellular and molecular Andrology are underway and one in prostate cancer. The Andrology projects involve 1) characterisation of the transcriptome or bovine, porcine and ovine sperm with an investigation into the role and fate of sperm RNA in the (bovine and ovine) embryo and 2) analysis of the chromatin and DNA integrity of sperm selected by hyaluronan. The Urology project involves the development of a non-invasive assay qPCR based procedure for assessing prostate health using luminal cells isolated from ejaculate semen and is a collaborative venture with MediPex.
Selection of sperm for Assisted Reproductive Treatment by prior hyaluronic acid binding: increasing live birth outcomes and reducing miscarriage rates multicentre randomised controlled, blinded trial.
National Institute for Health Research - Efficacy and Mechanism Evaluation Grant
A parallel randomised blinded trial of hyaluronan selected versus conventionally selected sperm in a clinical setting (10 assisted conception units) will test the efficacy of selected sperm at improving live birth outcomes. The same sperm samples will also be assessed for DNA fragmentation and packaging anomalies and the output data compared with the original samples hyaluronan binding score.
Huntriss J, Hinkins M, Picton HM.
cDNA cloning and expression of the human NOBOX gene in oocytes and ovarian follicles.
Mol Hum Reprod. 2006, 12(5):283-9
Arpanahi A, et al, Miller D.
Endonuclease-sensitive regions of human spermatozoal chromatin are highly enriched in promoter and CTCF binding sequences.
Genome Res 2009, 19:1338-1349
Picton HM, Elder K, Houghton FD, Hawkhead JA, Rutherford AJ, Hogg JE, Leese HJ and Harris SE.
Association between amino acid turnover and chromosome aneuploidy during human preimplantation embryo development in vitro.
Mol Hum Reprod 2010, 6(8):557-69.
Harris SE, Maruthini D, Tang T, Balen AH, Picton HM.
Metabolism and karyotype analysis of oocytes from patients with PCOS.
Hum Reprod 2010, 25(9):2305-15
Chambers EL, Gosden RG, Yap C, Picton HM.
In situ identification of follicles in ovarian cortex as a tool to quantify follicle density, viability and developmental potential in strategies to preserve female fertility.
Human Reproduction 2010, 25(10):2559-68
Huntriss J, Woodfine K, Huddleston JE, Murrell A, Rutherford AJ, Elder K, Khan AA, Hemmings K, Picton HM.
Quantitative analysis of DNA methylation of imprinted genes in single human blastocysts by pyrosequencing.
Fertil Steril. 2011 95(8):2564-7.
Saida M, et al, Miller D.
Key gene regulatory sequences with distinctive ontological signatures associate with differentially endonuclease-accessible mouse sperm chromatin.
Reproduction 2011, 142: 273-286.
Robinson L., et al, Miller D., Coomarasamy, A.
The effect of sperm DNA fragmentation on miscarriage rates: a systematic review and meta-analysis.
Hum Reprod 2012, 27: 2908-29177
Huntriss JD, Hemmings KE, Hinkins M, Rutherford AJ, Sturmey RG, Elder K, Picton HM
Variable imprinting of the MEST gene in human preimplantation embryos.
Eur J Hum Genet. 2013, 21(1):40-7
Hemmings KE, Maruthini D, Vyjayanthi S, Hogg JE, Balen AH, Campbell BK, Leese HJ, Picton HM.
Amino acid turnover by human oocytes is influenced by gamete developmental competence, patient characteristics and gonadotrophin treatment.
Hum Reprod 2013, 28(4):1031-44
Dr Niamh Forde