Research

researchThe ChRS team have made advances in various areas, these include achievements in:

  • Translational medicine, such as the invention of the male Fertell over-the-counter home fertility test.
  • The first detailed studies of ion channels in human sperm.
  • Detailed characterisation of the events occurring in sperm in response to steroid hormones, including the discovery of slow calcium oscillations, now thought to possibly regulate motility. To date the identity of the cell receptors involved has not been clearly elucidated.
  • Substantial follow-up data of children born through IVF treatment to check for increased risks associated with the treatment.
  • ChRS also has psychology collaborations to actively pursue research enabling better understanding of patient feelings and care during fertility treatment; and issues surrounding motivation to be a donor and receipt of donor gametes.

The ChRS does not directly enter into patient treatment or diagnosis being focussed upon research. These are delivered through the affiliated Birmingham Women's Fertility Centre at Birmingham Women’s Hospital

Current research projects:

Human gamete interaction and signalling...

The ChRS is an HFEA licenced centre for projects covering human gamete interaction and signalling, which will fulfil the purpose of;

-       Promoting advances in treatment of infertility

-       Developing more effective techniques of contraception

-       Increasing knowledge about the development of embryos                   

We hold National REC approval (Ref 13/EM/0272) as a tissue bank for this work. More detail can be found under the heading Reproductive Biomaterials Executive Committee (RBEC) 

HABSelect – comparing different methods of selecting sperm for ICSI...

Hab SelectThis is a multi-centre randomised blinded controlled trial. The main aim is to test a method which may increase the number of live births from treatment and reduce miscarriage rates by using a different method of selecting ‘good’ sperm. Secondly, we want to find out more about what makes these ‘good’ sperm different from the others. One possible difference may be how the DNA is packaged in the sperm cell or in the amount of damage that the sperm DNA caries. If it is the latter, then changes in lifestyle could potentially improve the couple’s chance of having a baby.

www.HABSelect.org.uk

Endometrial Fluid Metabolomics...

In IVF or ICSI treatment the goal is to produce a good quality embryo with artificial fertilization.  Following this, the embryo must implant into the womb in order for a pregnancy to be achieved.  This is a complex process leading to a high frequency of failed treatment.  It is this area which remains the rate limiting step in IVF treatment success. This has led to much research into the womb cavity environment and the factors that determine womb lining receptivity to an embryo.

Metabolomics is the study of substances that are present in any biological fluid.  The Endometrial Fluid Metabolomics project aims to study the pattern of substances that are present in the womb cavity fluid at the time of inserting an embryo.  We aim to find a particular pattern of metabolic substances which encourages successful IVF treatment.  Obtaining a better understanding of embryo implantation in IVF treatment may allow us to improve IVF treatment success in patients.

Publications...

E.H. Ooi, D.J. Smith, H. Gadelha, E.A. Gaffney and J. Kirkman-Brown (2014) The mechanics of hyperactivation in adhered human sperm. R. Soc. Open Sci. 1:140230

P. Sampaio, R.R. Ferreira, A. Guerrero, P. Pintado, B. Tavares, J. Amaro, A. Smith, T.D. Montenegro-Johnson, D.J. Smith and S. Lopes (2014) Left-Right organizer flow dynamics: How much cilia activity reliably yields laterality? Dev. Cell, 29, 716-728

D.J. Smith, T.D. Montenegro-Johnson and S.S. Lopes (2014) Organized chaos in Kupffer's vesicle: how a heterogeneous structure achieves consistent left-right patterning. Bioarchitecture, to appear, doi: 10.4161/19490992.2014.956593

Duffy B, Thiyagalingam J, Walton S, Smith DJ, Trefethen A, Kirkman-Brown JC, Gaffney EA, Chen M. Glyph-Based Video Visualization for Semen Analysis. IEEE Trans Vis Comput Graph. 2013 Dec 12. [Epub ahead of print] PubMed PMID: 24344092.

Alasmari W, Costello S, Correia J, Oxenham SK, Morris J, Fernandes L, Ramalho-Santos J, Kirkman-Brown J, Michelangeli F, Publicover S, Barratt CL. Ca2+ signals generated by CatSper and Ca2+ stores regulate different behaviors in human sperm. J Biol Chem. 2013 Mar 1;288(9):6248-58. doi:10.1074/jbc.M112.439356. Epub 2013 Jan 23. PubMed PMID: 23344959; PubMed Central PMCID: PMC3585060.

T.D. Montenegro-Johnson, D.J. Smith and D. Loghin (2013) Physics of rheologically-enhanced propulsion: different strokes in generalized Stokes. Phys. Fluids. 25, 081903

Lefièvre L, Nash K, Mansell S, Costello S, Punt E, Correia J, Morris J, Kirkman-Brown J, Wilson SM, Barratt CL, Publicover S. 2-APB-potentiated channels amplify CatSper-induced Ca(2+) signals in human sperm. Biochem J. 2012 Dec 1;448(2):189-200. doi: 10.1042/BJ20120339. PubMed PMID: 22943284; PubMed Central PMCID: PMC3492921.

Denissenko P, Kantsler V, Smith DJ, Kirkman-Brown J. Human spermatozoa migration in microchannels reveals boundary-following navigation. Proc Natl Acad Sci U S A. 2012 May 22;109(21):8007-10. doi: 10.1073/pnas.1202934109. Epub 2012 May 7. PubMed PMID: 22566658; PubMed Central PMCID: PMC3361448.

Robinson L, Gallos ID, Conner SJ, Rajkhowa M, Miller D, Lewis S, Kirkman-Brown J, Coomarasamy A. The effect of sperm DNA fragmentation on miscarriage rates: a systematic review and meta-analysis. Hum Reprod. 2012 Oct;27(10):2908-17. doi: 10.1093/humrep/des261. Epub 2012 Jul 12. Review. PubMed PMID: 22791753.

T.D. Montenegro-Johnson, A.A. Smith, D.J. Smith and J.R. Blake (2012) Modelling the Fluid Mechanics of Cilia and Flagella in Reproduction and Development. Eur. Phys. J. E. 35:111

A.A. Smith, T.D. Johnson, D.J. Smith and J.R. Blake (2012) Symmetry-breaking cilia-driven flow in the zebrafish embryo. J. Fluid Mech. 705, 26-45

Kirkman-Brown JC, Smith DJ. Sperm motility: is viscosity fundamental to progress? Mol Hum Reprod. 2011 Aug;17(8):539-44. doi: 10.1093/molehr/gar043. Epub2011 Jun 8. Review. PubMed PMID: 21653751.  

D.J. Smith, A.A. Smith and J.R. Blake (2011) Mathematical embryology: the fluid mechanics of nodal cilia. J. Eng. Math 70, 255-279

Nash K, Lefievre L, Peralta-Arias R, Morris J, Morales-Garcia A, Connolly T, Costello S, Kirkman-Brown JC, Publicover SJ. Techniques for imaging Ca2+ signaling in human sperm. J Vis Exp. 2010 Jun 16;(40). pii: 1996. doi: 10.3791/1996. PubMed PMID: 20567212; PubMed Central PMCID: PMC3153901.

Lefièvre L, Machado-Oliveira G, Ford C, Kirkman-Brown J, Barratt C, Publicover S. Communication between female tract and sperm: Saying NO* when you mean yes. Commun Integr Biol. 2009;2(2):82-5. PubMed PMID: 19704895; PubMed Central PMCID: PMC2686350.

Costello S, Michelangeli F, Nash K, Lefievre L, Morris J, Machado-Oliveira G, Barratt C, Kirkman-Brown J, Publicover S. Ca2+-stores in sperm: their identities and functions. Reproduction. 2009 Sep;138(3):425-37. doi: 10.1530/REP-09-0134. Epub 2009 Jun 19. Review. PubMed PMID: 19542252; PubMed Central PMCID: PMC3552241.

Kirkman-Brown J, Björndahl L. Evaluation of a disposable plastic Neubauer counting chamber for semen analysis. Fertil Steril. 2009 Feb;91(2):627-31. doi: 10.1016/j.fertnstert.2007.11.076. Epub 2008 Apr 25. PubMed PMID: 18439603.

Machado-Oliveira G, Lefièvre L, Ford C, Herrero MB, Barratt C, Connolly TJ, Nash K, Morales-Garcia A, Kirkman-Brown J, Publicover S. Mobilisation of Ca2+ stores and flagellar regulation in human sperm by S-nitrosylation: a role for NO synthesised in the female reproductive tract. Development. 2008 Nov;135(22):3677-86. doi: 10.1242/dev.024521. Epub 2008 Oct 8. PubMed PMID: 18842814; PubMed Central PMCID: PMC2777309.

Bowdin S, Allen C, Kirby G, Brueton L, Afnan M, Barratt C, Kirkman-Brown J, Harrison R, Maher ER, Reardon W. A survey of assisted reproductive technology births and imprinting disorders. Hum Reprod. 2007 Dec;22(12):3237-40. Epub 2007 Oct 5. PubMed PMID: 17921133.  

Ellis PJ, Furlong RA, Conner SJ, Kirkman-Brown J, Afnan M, Barratt C, Griffin DK, Affara NA. Coordinated transcriptional regulation patterns associated with infertility phenotypes in men. J Med Genet. 2007 Aug;44(8):498-508. Epub 2007 May 11. PubMed PMID: 17496197; PubMed Central PMCID: PMC2597934.

Lefièvre L, Bedu-Addo K, Conner SJ, Machado-Oliveira GS, Chen Y, Kirkman-Brown JC, Afnan MA, Publicover SJ, Ford WC, Barratt CL. Counting sperm does not add up any more: time for a new equation? Reproduction. 2007 Apr;133(4):675-84. Review. PubMed PMID: 17504912.

Meng F, To W, Kirkman-Brown J, Kumar P, Gu Y. Calcium oscillations induced by ATP in human umbilical cord smooth muscle cells. J Cell Physiol. 2007 Oct;213(1):79-87. PubMed PMID: 17477379.

Correia JN, Conner SJ, Kirkman-Brown JC. Non-genomic steroid actions in human spermatozoa. "Persistent tickling from a laden environment". Semin Reprod Med. 2007 May;25(3):208-19. Review. PubMed PMID: 17447210.

Harper CV, Barratt CL, Publicover SJ, Kirkman-Brown JC. Kinetics of the progesterone-induced acrosome reaction and its relation to intracellular calcium  responses in individual human spermatozoa. Biol Reprod. 2006 Dec;75(6):933-9. Epub 2006 Sep 6. PubMed PMID: 16957023.

Barratt CL, Kirkman-Brown J. Man-made versus female-made environment—will the real capacitation please stand up? Hum Reprod Update. 2006 Jan-Feb;12(1):1-2. PubMed PMID: 16354709.

Kirkman-Brown JC, Barratt CL, Publicover SJ. Slow calcium oscillations in human spermatozoa. Biochem J. 2004 Mar 15;378(Pt 3):827-32. PubMed PMID: 14606954; PubMed Central PMCID: PMC1223996.

Harper CV, Kirkman-Brown JC, Barratt CL, Publicover SJ. Encoding of progesterone stimulus intensity by intracellular [Ca2+] ([Ca2+]i) in human spermatozoa. Biochem J. 2003 Jun 1;372(Pt 2):407-17. PubMed PMID: 12614198; PubMed Central PMCID: PMC1223411.

Kirkman-Brown JC, Sutton KA, Florman HM. How to attract a sperm. Nat Cell Biol. 2003 Feb;5(2):93-6. PubMed PMID: 12563269.

Kirkman-Brown JC, Punt EL, Barratt CL, Publicover SJ. Zona pellucida and progesterone-induced Ca2+ signaling and acrosome reaction in human spermatozoa. J Androl. 2002 May-Jun;23(3):306-15. Review. PubMed PMID: 12002428.