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Male Infertility & Germ Cell Biology Laboratory

Professor Moira O'Bryan

We study sperm development and function and the causes of human male infertility.

 

Approximately 1 in 20 Australian men are infertile and for the majority of these individuals, there is no specific diagnosis. Sperm development is a fascinating process that requires the co-ordinated activation of thousands of genes. It involves stem cell renewal, meiosis, cell changes and complex post-translational mechanisms, which regulate sperm function. We use models of infertility and cell biology assays to define key proteins and pathways for fertility. This research has direct implications for the diagnosis of human infertility, and the development of therapies and contraceptives.

 

Spermatogenesis

Research Group

Research Fellows

Dr Duangporn Jamsai

Dr Kathleen DeBoer

Dr Adam Koppers

 

Research Assistants

Ms Stephanie Smith

Ms Anne O’Connor

Ms Jo Merriner

Mr Brett Clark

Mr Francesco Marino

 

PhD Students

Ms Jennifer Lo

 

Spermatogenesis

Grants

NHMRC Project Grant:

·     Cysteine-rich secretory protein regulation of ion channels in male fertility and prostate cancer. (2010-2012)

·     A new model of asthenospermia and a candidate gene for multiple ciliopathies. (2010-2012)

·     Human sperm-oocyte interaction (2009-2011).

 

ARC Discovery Grant:

·     A novel DNA damage repair protein as a regulator of DNA double strand break repair and genome integrity. (2011-2013)

 

Monash IVF Research Grant:

·     Studies on the genetic basis of male and idiopathic infertility, and the trans-generational health of children conceived through ART.

 

NHMRC Enabling Grants:

·     Australian Centre for Vertebrate Mutation Detection (2007-2011).

·     ‘The Australian Phenome Bank’ (2010-2011)

 

National Collaborative Research Infrastructure Scheme:

·     Extension for the Australian Phenomics Network. (2010-2011)

 

Education Investment Fund:

·     Infrastructure grant to underpin the Australian Phenomics Network. (2010-2113)

 

Spermatogenesis

Publications

Professor Moira O'Bryan

2011

 

Mouse models in male fertility research. Asian J Androl 2011; 13(1): 139-151. Jamsai D, O'Bryan MK.

 

The role of cysteine-rich secretory proteins in male fertility. Asian J Androl 2011; 13(1): 111-117. Koppers AJ, Reddy T, O'Bryan MK.

  

TRPM8 in mouse sperm detects temperature changes and may influence the acrosome reaction.  J Cell Physiol 2011; 226(6): 1620-31. Martínez-López P, Treviño CL, de la Vega-Beltrán JL, De Blas G, Beltrán C, Orta G, Gibbs GM, O’Bryan MK, Darszon A.

  

GGN1 in the testis and ovary and its variance within the Australian fertile and infertile male population. Int J Andrology 201; (Epub ahead of print). Jamsai D, Sarraj MA, Merriner DJ, Drummond AE, Jones KT, McLachlan RI, O’Bryan MK.

 

Spermiation: The process of sperm release. Spermatogenesis 2011; 1(1): 14-35. O'Donnell L, Nicholls PK, O'Bryan MK, McLachlan RI, Stanton PG.

 

Proteomic and functional analysis of human sperm detergent resistant membranes. J Cell Physiol 2011; (Epub ahead of print). Nixon B, Mitchell L, Anderson A, McLaughlin EA, O’Bryan MK, Aitken RJ.

 

DNMT3L is a regulator of X chromosome compaction and post-meiotic gene transcription. PLoS One 2011; 6(3): e18276. Zamudio NM, Scott HS, Wolski K, Lo JC, Law C, Leong D, Kinkel S, Chong S, Jolley D, Smyth GK, de Kretser DM, Whitelaw E, O’Bryan MK.

  

Generation of stable pluripotent stem cells from non-obese diabetic (NOD) mouse tail-tip fibroblasts. Diabetes 2011; 60(5):1393-8.  Liu J, Aston MP, Sumer H, O’Bryan MK, Brodnicki TC, Verma PJ.

  

CRISP4 inhibits transient receptor potential M8 (TRPM8) ion flow in mouse sperm. Proceedings of the National Academy of Sciences 2011; 108(17): 7034-9. Gibbs GM, Orta G, Reddy T, Koppers AJ, Martinez P, de la Vega-Beltran JL, Lo JCL, Veldhuis N, McIntyre P, Darszon A, O’Bryan MK.

 

Involvement of multimeric protein complexes in mediating the capacitation-dependent binding of human spermatozoa to homologous zonae pellucidae. Developmental Biology 2011; (in press). Redgrove KA, McLaughlin EA, O’Bryan MK, Aitken RJ, Nixon B.

  

The generation of live offspring from vitrified oocytes. PLOS One 2011; 6(6). Sanchez-Partida LG, Kelly R, Sumer H, Holland MK, O’Bryan MK, St. John JC.

 

2010

 

Mouse models as tools in fertility research and male-based contraceptive development. Handb Exp Pharmacol 2010; 198: 179-194. Jamsai D, O'Bryan MK.

 

Proteomic and functional analysis of human sperm detergent resistant membranes. J Cell Physiol 2010. Nixon B, Mitchell LA, Anderson A, McLaughlin EA, O’Bryan MK, Aitken RJ.

 

Deletion of the Parkin co-regulated gene causes defects in ependymal ciliary motility and hydrocephalus in the quakingviable mutant mouse. Hum Mol Genet 2010; 19 (8): 1593-1602. Wilson GR, Wang HX, Egan GF, Robinson PJ, Delatycki MB, O'Bryan MK, Lockhart PJ.

 

Vinclozolin exposure in utero induces postpubertal prostatitis and reduces sperm production via a reversible hormone-regulated mechanism. Endocrinology 2010; 151 (2): 783-792. Cowin PA, Gold E, Aleksova J, O'Bryan MK, Foster PM, Scott HS, Risbridger GP.

 

Genome-wide ENU mutagenesis for the discovery of novel male fertility regulators. Syst Biol Reprod Med 2010; 56 (3): 246-259. Jamsai D, O'Bryan MK.

 

Clinical Review#: State of the art for genetic testing of infertile men. J Clin Endocrinol Metab 2010; 95 (3): 1013-1024. McLachlan RI, O'Bryan MK.

 

Phenotyping male infertility in the mouse: how to get the most out of a 'non-performer'. Hum Reprod Update 2010; 16 (2): 205-224. Borg CL, Wolski KM, Gibbs GM, O'Bryan MK.

 

Glioma pathogenesis-related 1-like 1 is testis enriched, dynamically modified, and redistributed during male germ cell maturation and has a potential role in sperm-oocyte binding. Endocrinology 2010; 151 (5): 2331-2342. Gibbs GM, Lo JC, Nixon B, Jamsai D, O'Connor AE, Rijal S, Sanchez-Partida LG, Hearn MT, Bianco DM, O'Bryan MK.

 

Molecular analysis of the PArkin co-regulated gene and association with male infertility. Fertil Steril 2010; 93 (7): 2262-2268. Wilson GR, Sim ML, Brody KM, Taylor JM, McLachlan RI, O'Bryan MK, Delatycki MB, Lockhart PJ.

 

2009

 

A novel protein, sperm head and tail associated protein (SHTAP), interacts with cysteine-rich secretory protein 2 (CRISP2) during spermatogenesis in the mouse. Biol Cell 2009;102 (2): 93-106. Jamsai D, Rijal S, Bianco DM, O'Connor AE, Merriner DJ, Smith SJ, Gibbs GM, O'Bryan MK.

 

Activin C antagonizes activin A in vitro and overexpression leads to pathologies in vivo. Am J Pathol 2009; 174 (1): 184-195. Gold E, Jetly N, O'Bryan MK, Meachem S, Srinivasan D, Behuria S, Sanchez-Partida LG, Woodruff T, Hedwards S, Wang H, McDougall H, Casey V, Niranjan B, Patella S, Risbridger G.

 

Phenotypic variation within European carriers of the Y-chromosomal gr/gr deletion is independent of Y-chromosomal background. J Med Genet 2009; 46 (1): 21-31. Krausz C, Giachini C, Xue Y, O'Bryan MK, Gromoll J, Rajpert-de Meyts E, Oliva R, Aknin-Seifer I, Erdei E, Jorgensen N, Simoni M, Ballesca JL, Levy R, Balercia G, Piomboni P, Nieschlag E, Forti G, McLachlan R, Tyler-Smith C.

 

Aire-deficient C57BL/6 mice mimicking the common human 13-base pair deletion mutation present with only a mild autoimmune phenotype. J Immunol 2009; 182 (6): 3902-3918. Hubert FX, Kinkel SA, Crewther PE, Cannon PZ, Webster KE, Link M, Uibo R, O'Bryan MK, Meager A, Forehan SP, Smyth GK, Mittaz L, Antonarakis SE, Peterson P, Heath WR, Scott HS.

 

2008

 

Inflammatory networks in the control of spermatogenesis : chronic inflammation in an immunologically privileged tissue? Adv Exp Med Biol 2008; 636: 92-114. O'Bryan MK, Hedger MP.

 

Cellular signaling by fibroblast growth factors (FGFs) and their receptors (FGFRs) in male reproduction. Endocr Rev 2008; 29 (2): 193-216. Cotton LM, O'Bryan MK, Hinton BT.

 

Sox8 is a critical regulator of adult Sertoli cell function and male fertility. Dev Biol 2008; 316 (2): 359-370. O'Bryan MK, Takada S, Kennedy CL, Scott G, Harada S, Ray MK, Dai Q, Wilhelm D, de Kretser DM, Eddy EM, Koopman P, Mishina Y.

 

Epigenetic regulation in male germ cells. Reproduction 2008; 136 (2): 131-146. Zamudio NM, Chong S, O'Bryan MK.

 

The CAP superfamily: cysteine-rich secretory proteins, antigen 5, and pathogenesis-related 1 proteins--roles in reproduction, cancer, and immune defense. Endocr Rev 2008; 29 (7): 865-897. Gibbs GM, Roelants K, O'Bryan MK.

 

Characterization of gametogenetin 1 (GGN1) and its potential role in male fertility through the interaction with the ion channel regulator, cysteine-rich secretory protein 2 (CRISP2) in the sperm tail. Reproduction 2008; 135 (6): 751-759. Jamsai D, Bianco DM, Smith SJ, Merriner DJ, Ly-Huynh JD, Herlihy A, Niranjan B, Gibbs GM, O'Bryan MK.

 

Identification of the molecular chaperone, heat shock protein 1 (chaperonin 10), in the reproductive tract and in capacitating spermatozoa in the male mouse. Biol Reprod 2008; 78 (6): 983-993. Walsh A, Whelan D, Bielanowicz A, Skinner B, Aitken RJ, O'Bryan MK, Nixon B.

 

Cysteine-rich secretory proteins are not exclusively expressed in the male reproductive tract. Dev Dyn 2008; 237 (11): 3313-3323. Reddy T, Gibbs GM, Merriner DJ, Kerr JB, O'Bryan MK.

 

Polymorphisms in the human cysteine-rich secretory protein 2 (CRISP2) gene in Australian men. Hum Reprod 2008; 23 (9): 2151-2159. Jamsai D, Reilly A, Smith SJ, Gibbs GM, Baker HW, McLachlan RI, de Kretser DM, O'Bryan MK.

 

2007

 

Cysteine rich secretory proteins in reproduction and venom. Soc Reprod Fertil Suppl 2007; 65: 261-267. Gibbs GM, O'Bryan MK.

 

The testis and epididymis are productively infected by SIV and SHIV in juvenile macaques during the post-acute stage of infection. Retrovirology 2007; 4: 7. Shehu-Xhilaga M, Kent S, Batten J, Ellis S, Van der Meulen J, O'Bryan M, Cameron PU, Lewin SR, Hedger MP.

 

Sox8 and Sertoli-cell function. Ann N Y Acad Sci 2007; 1120: 104-113. Kennedy CL, Koopman P, Mishina Y, O'Bryan MK.

 

Cysteine-rich secretory protein 2 binds to mitogen-activated protein kinase kinase kinase 11 in mouse sperm. Biol Reprod 2007; 77 (1): 108-114. Gibbs GM, Bianco DM, Jamsai D, Herlihy A, Ristevski S, Aitken RJ, Kretser DM, O'Bryan MK.

 

Modifiers of epigenetic reprogramming show paternal effects in the mouse. Nat Genet 2007; 39 (5): 614-622. Chong S, Vickaryous N, Ashe A, Zamudio N, Youngson N, Hemley S, Stopka T, Skoultchi A, Matthews J, Scott HS, de Kretser D, O'Bryan M, Blewitt M, Whitelaw E.

 

Constitutive expression of prostaglandin-endoperoxide synthase 2 by somatic and spermatogenic cells is responsible for prostaglandin E2 production in the adult rat testis. Biol Reprod 2007; 76 (5): 759-768. Winnall WR, Ali U, O'Bryan MK, Hirst JJ, Whiley PA, Muir JA, Hedger MP.

 

Sperm