Translational studies in male infertility
Male infertility is a leading cause of human infertility and solely or partly accounts for half of all Assisted Reproduction Technologies (ART) procedures. Most cases are due to reduced sperm number, motility and/or the inability of sperm to fertile an oocyte (egg) and initiate normal embryonic development.
The bulk of cases are unexplained but a genetic basis for many cases is suspected. To date only 10 per cent can be explained by disorders of chromosomal number or structure, and partial deletions of the long arm of the Y (male) sex chromosome account and a few specific gene defects.
Over many years the team has developed a repository of genomic DNA and clinical information from over 2000 infertile men, their partners and their ART-conceived children for use in such genetic studies. This repository is being used to identify genetic causes of male infertility. Specific research areas include assessment for mutations in genes involved in DNA repair and sperm tail development and the involvement of small non-coding RNAs in sperm development and function.
This research also focuses on the importance of genetic instability and epigenetic imprinting in male infertility. Importantly this research also has consequences for understanding the impact of ART on the health of the next generation.
Studies on the genetic basis of male infertility may lead to better diagnostic tests and treatment for the infertile couples and is also essential in ensuring couples undertaking ART are fully informed about the likely health of their offspring.
Prof John Aitken – The University of Newcastle
Prof David de Kretser – Hudson Institute of Medical Research
Dr Duangporn Jamsai – Monash University
Prof Moira O’Bryan – Monash University
Dr Liza O’Donnell – Hudson Institute of Medical Research
Jamsai D, Lo JC, McLachlan RI, O’Bryan MK. Genetic variants in the RABL2A gene in fertile and oligoasthenospermic infertile men Fertility and Sterility (2014) 102(1):223-9
Jamsai D, Grealy A, Stahl PJ, Schlegel PN, McLachlan RI, Morand E* and O’Bryan MK*. (*Equal last author) Genetic variants in the human glucocorticoid-induced leucine zipper (GILZ) gene in fertile and infertile men Andrology (2013) 1 (3): 451-5
McLachlan RI, Ishikawa T, Osianlis T, Robinson P, Merriner DJ, Healy D, de Kretser D, O’Bryan MK. Normal live birth after testicular sperm extraction and intracytoplasmic sperm injection in variant primary ciliary dyskinesia with completely immotile sperm and structurally abnormal sperm tails. Fertility and Sterility (2012) 97(2):313-318.
O’Bryan MK, Grealy A, Stahl PJ, Schlegel PN, McLachlan RI, Jamsai D. Genetic variants in the ETV5 gene in fertile and infertile men with non-obstructive azoospermia associated with Sertoli cell only syndrome Fertility and Sterility (2012) 98 (4): 827-35
Jamsai D, Sarraj MA, Merriner DJ, Drummond AE, Jones KT, McLachlan RI, O’Bryan MK GGN1 in the testis and ovary and its variance within the Australian fertile and infertile male population. International Journal of Andrology (2011) 34(6):624-32.
McLachlan RI, O’Bryan MK . (2010) State of the Art for Genetic Testing of Infertile Men. J Clin Endocrinol Metab. 95(3): 1013-24
Wilson GR, Sim ML, Brody KM, Taylor JM, McLachlan RI, O’Bryan MK, Delatycki MB, Lockhart PJ. Molecular analysis of the PArkin co-regulated gene and association with male infertility. Fertility and Sterility (2010) 93(7): 2262-68.
Jamsai D, Reilly A, Smith SJ, Gibbs GM, Baker HW, McLachlan RI, de Kretser DM, O’Bryan MK.. Polymorphisms in the human cysteine-rich secretory protein 2 (CRISP2) gene in Australian men. Molecular Human Reproduction (2008) 23:2151-2159.
McLachlan RI, de Kretser DM. (2006) Hypogonadotropism with elevated serum testosterone: reversible causes of secondary infertility. Nat Clin Pract Urol. 3: 560-565