Professor William V. Holt

Curriculum Vitae:

• 1995-2011: Head of Reproductive Biology. Institute of Zoology, Zoological Society of London.
• 1983-1995: Research Fellow, Reproductive Biology Group, Institute of Zoology, Zoological Society of London.
• 1975-1979: PhD(Univ. London); Royal Veterinary College, London.
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Offices held; Professional Organisations:

• 2004-2009: Chairman of the British Andrology Society.
• 1991-1996: Secretary of The British Andrology Society.
• 1996-1998: Committee member of The British Andrology Society.
• 1993-2002: Founder member of "UK Pig Reproduction Research Liaison Group"; an advisory committee of 8 representatives from research, industry and funding organizations.
• 1999-2002: Committee member of The Society for Low Temperature Biology.
• July 2004-Date: Chairman of The British Andrology Society.
• 2002-Date: Co-Chair (with Dr Naida Loskutoff) of the Health and Safety subcommittee of the CANDES (Companion and Domestic Animals and Endangered Species) of the International Embryo Transfer Society.
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Research Interests:

The ability to store spermatozoa and use it to support captive breeding programmes for the conservation of small populations requires in-depth knowledge of the mechanisms which govern sperm survival during the freeze-thaw process. My work in this area has been directed towards defining underlying principles which influence sperm survival, rather than taking the empirical approach which has characterised this field for many years. In this context, I developed the use of cryomicroscopy for spermatozoa, and have recently used it to demonstrate that problems with the cryostorage of macropod spermatozoa are largely caused by plasma membrane instability during the warming process. A narrow temperature threshold marks the destabilisation point, and further research has indicated that the disruption of submembranous cytoskeletal- lipid interactions may be responsible for this effect.

In addition to undertaking research in this area I have also been involved with international efforts to promote and coordinate the applications of genome resource banking for conservation. Thus I have ongoing interactions with the Australian centres which are concerned with conservation of their native fauna (i.e. Monash University, University of Queensland, Macquarie University), and have taken an active role in their research projects over the past 4-5 years.

I have a broad interest in understanding the cellular mechanisms involved in the processes which lead to fertilisation. It is my belief that understanding these processes will be best achieved by studying sperm development from the earliest stages of spermatogenesis right through to the moment of syngamy. The spermatozoon offers a unique model with which to work, since it lacks the capacity for protein synthesis; this means that the components of every signalling pathway required for fertilisation must be synthesised in advance, ready for activation or inactivation later in the developmental sequence.

To study these areas in depth I have been able to initiate projects which address the interaction between developing germ cells and the supporting Sertoli cells, the dialogue between the spermatozoon and the oviduct, and also to investigate cellular signalling pathways which control sperm motility. The latter has been enabled by the development of objective systems for measuring and characterising the motion of individual spermatozoa, thereby allowing the differential responses of sperm subpopulations to be studied. This latter point has a significant impact upon studies of sperm competition.
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Publications:

Allen CD, Burridge M, et al. (2008) Control of the koala (Phascolarctos cinereus) anterior pituitary-gonadal axis with analogues of GnRH. Reprod Fertil Dev 20, 598-605.

Allen CD, Burridge M, et al. (2008) Successful artificial insemination in the koala (Phascolarctos cinereus) using extended and extended-chilled semen collected by electroejaculation. Biol Reprod 78, 661-6.

Coy P, Lloyd R, Romar R, Matas C, Adan AG, Holt WV (2008) Bovine oviductal fluid affects quality and gene expression of in vitro derived porcine blastocysts. Reproduction in Domestic Animals 43, 66-66.

Dzyuba BB, Van Look KJW, Kholodnyy VS, Satake N, Cheung S, Holt WV (2008) Variable sperm size and motility activation in the pipefish, Syngnathus abaster; adaptations to paternal care or environmental plasticity? Reproduction Fertility and Development 20, 474-482.

Elliott RM, Lloyd RE, Fazeli A, Sostaric E, Georgiou AS, Satake N, Watson PF, Holt WV (2009) Effects of HSPA8, an evolutionarily conserved oviductal protein, on boar and bull spermatozoa. Reproduction 137, 191-203.

Gosalvez J, Cortes-Gutierrez EI, Nunez R, Fernandez JL, Caballero P, Lopez-Fernandez C, Holt WV (2009) A dynamic assessment of sperm DNA fragmentation versus sperm viability in proven fertile human donors. Fertil Steril 92, 1915-9.

Hala DN, Van Look K, Holt WV, Jobling S (2009) Validation of a method for measuring sperm quality and quantity in reproductive toxicity tests with pair-breeding male fathead minnows (Pimephales promelas). Ilar J 50, e1-e10.

Holt WV (2008) Cryobiology, wildlife conservation and reality. CryoLetters 29, 43-52.

Holt WV (2008) How do we Test Sperm Samples for 'Fertility'? Reproduction in Domestic Animals 43, 106-106.

Holt WV (2009) Is semen analysis useful to predict the odds that the sperm will meet the egg? Reprod Domest Anim 44 Suppl 3, 31-8.

Holt WV, Green D (2008) Successful cell cultures for the Frozen Ark project derived from tissues collected 1-4 days post-mortem and stored at-80 degrees C for several months. Cryoletters 29, 85-85.

Holt WV, Hernandez M, Warrell L, Satake N (2010) The long and the short of sperm selection in vitro and in vivo: swim-up techniques select for the longer and faster swimming mammalian sperm. Journal of Evolutionary Biology 23, 598-608.

Holt WV, Lloyd RE (2009) Artificial insemination for the propagation of CANDES: the reality! Theriogenology 71, 228-235.

Holt WV, Lloyd RE (2010) Sperm storage in the vertebrate female reproductive tract: How does it work so well? Theriogenology 73, 713-722.

Holt WV, O'Brien J, Abaigar T (2007) Applications and interpretation of computer-assisted sperm analyses and sperm sorting methods in assisted breeding and comparative research. Reprod Fertil Dev 19, 709-18.

Johnston SD, Lopez-Fernandez C, Gosalbez A, Zee YP, Holt WV, Allen C, Gosalvez J (2007) The relationship between sperm morphology and chromatin integrity in the koala (Phascolarctos cinereus) as assessed by the sperm chromatin dispersion test (SCDt). Journal of Andrology 28, 891-899.

Johnston SD, Smith B, Pyne M, Stenzel D, Holt WV (2007) One-sided ejaculation of echidna sperm bundles. American Naturalist 170, E162-E164.

Lermen D, Blomeke B, et al. (2009) Cryobanking of viable biomaterials: implementation of new strategies for conservation purposes. Molecular Ecology 18, 1030-1033.

Lloyd RE, Badia E, Fazeli A, Watson PF, Holt WV (2008) Temporal dynamics of ram sperm binding and survival during 48-h coculture with oviducal epithelial cells. Reprod Fertil Dev 20, 835-45.

Lloyd RE, Badia E, Watson PF, Holt WV (2007) Prolonging the life of ram spermatozoa in vitro using oviductal epithelial cells. Reproduction Fertility and Development 19, 278-278.

Lloyd RE, Elliott RMA, Fazeli A, Watson PF, Holt WV (2009) Effects of oviductal proteins, including heat shock 70 kDa protein 8, on survival of ram spermatozoa over 48 h in vitro. Reproduction Fertility and Development 21, 408-418.

Lloyd RE, Romar R, Matas C, Gutierrez-Adan A, Holt WV, Coy P (2009) Effects of oviductal fluid on the development, quality, and gene expression of porcine blastocysts produced in vitro. Reproduction 137, 679-687.

Lloyd RE, Watson PF, Holt WV (2008) Heat shock cognate 70 protein improves the long-term survival of ram spermatozoa during storage at 17 degrees C in a commercial extender. Reproduction Fertility and Development 20, 88-88.

Lopez-Fernandez C, Fernandez JL, Gosalbez A, Arroyo F, Vazquez JM, Holt WV, Gosalvez J (2008) Dynamics of sperm DNA fragmentation in domestic animals III. Ram. Theriogenology 70, 898-908.

McClean R, Holt WV, Zee YP, Lisle A, Johnston SD (2008) The effect of cryoprotectant on kangaroo sperm ultrastructure and mitochondrial function. Cryobiology 57, 297-303.

McClean R, Zee YP, Holt WV, Johnston SD (2008) Cryopreservation of kangaroo spermatozoa using alternative approaches that reduce cytotoxic exposure to glycerol. Cryobiology 57, 304-307.

McClean RV, Holt WV, Johnston SD (2007) Ultrastructural observations of cryoinjury in kangaroo spermatozoa. Cryobiology 54, 271-80.

Medrano A, Holt WV, Watson PF (2009) Controlled freezing studies on boar sperm cryopreservation. Andrologia 41, 246-250.

Milligan SR, Holt WV, Lloyd R (2009) Impacts of climate change and environmental factors on reproduction and development in wildlife. Philosophical Transactions of the Royal Society B: Biological Sciences 364, 3313-3319.

Pickard AR, Holt WV (2007) Contraception in wildlife. Journal of Family Planning and Reproductive Health Care 33, 48-52.

Prathalingam NS, Watson PF, Revell SG, Busby J, Holt WV (2007) The response of bovine spermatozoa to bicarbonate and its use to assess the influence of added oviductal epithelial proteins on cryopreservation. Journal of Andrology 28, 407-415.

Santos EM, Paull GC, Van Look KJW, Workman VL, Holt WV, Van Aerle R, Kille P, Tyler CR (2007) Gonadal transcriptome responses and physiological consequences of exposure to oestrogen in breeding zebrafish (Danio rerio). Aquatic Toxicology 83, 134-142.

Satake N, Alhaider AK, Holt WV, Watson PF (2007) Exposure of spermatozoa to solubilized extracts of the oviductal epithelium apical plasma membrane enhances fertilization in porcine in vitro fertilization. Reproduction Fertility and Development 19, 272.

Satake N, Johnston SD, Holt WV (2009) Sperm Subpopulations in the Koala (Phascolarctos Cinereus) Ejaculate. Reproduction Fertility and Development 21, 213-214.

Satake N, Watson PF, Holt WV (2008) Phosphoinositide-3-kinase signaling and the control of sperm motility in the porcine oviduct. Reproduction Fertility and Development 20, 193.

Seytanoglu A, Georgiou AS, Sostaric E, Watson PF, Holt WV, Fazeli A (2008) Oviductal cell proteome alterations during the reproductive cycle in pigs. Journal of Proteome Research 7, 2825-2833.

van Dorsser FJD, Green DI, Holt WV, Pickard AR (2007) Ovarian activity in Arabian leopards (Panthera pardus nimr): sexual behaviour and faecal steroid monitoring during the follicular cycle, mating and pregnancy. Reproduction Fertility and Development 19, 822-830.

Van Look KJW, Dzyuba B, Cliffe A, Koldewey HJ, Holt WV (2007) Dimorphic sperm and the unlikely route to fertilisation in the yellow seahorse. Journal of Experimental Biology 210, 432-437.

Yeates SE, Einum S, Fleming IA, Megens HJ, Stet RJM, Hindar K, Holt WV, Van Look KJW, Gage MJG (2009) Atlantic salmon eggs favour sperm in competition that have similar major histocompatibility alleles. Proceedings of the Royal Society B-Biological Sciences 276, 559-566.

Yeste M, Lloyd RE, Badia E, Briz M, Bonet S, Holt WV (2009) Direct contact between boar spermatozoa and porcine oviductal epithelial cell (OEC) cultures is needed for optimal sperm survival in vitro. Animal Reproduction Science 113, 263-278.

Yeste M, Lloyd RE, Briz M, Badia E, Bonet S, Holt WV (2008) Boar sperm quality after co-culture with homologous oviductal epithelial cells. Theriogenology 70, 1395-1395.

Yeste M, Lloyd RE, Briz M, Bonet S, Holt WV (2008) The changes in the expression of three heat shock proteins during in vitro homologous oviductal epithelial cell co-culture. Reproduction in Domestic Animals 43, 53-53.

Zee YP, Holt WV, Allen CD, Nicolson V, Burridge M, Lisle A, Carrick FN, Johnston SD (2007) Effects of cryopreservation on mitochondrial function and heterogeneity, lipid raft stability and phosphatidylserine translocation in koala (Phascolarctos cinereus) spermatozoa. Reprod Fertil Dev 19, 850-60.

Zee YP, Holt WV, Gosalvez J, Allen CD, Nicolson V, Pyne M, Burridge M, Carrick FN, Johnston SD (2008) Dimethylacetamide can be used as an alternative to glycerol for the successful cryopreservation of koala (Phascolarctos cinereus) spermatozoa. Reproduction Fertility and Development 20, 724–733.

Zee YP, Lopez-Fernandez C, Gosalvez J, Holt WV, Johnston SD (2009) DNA Fragmentation Dynamics of Koala Spermatozoa. Reproduction Fertility and Development 21, 141-142.