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Regulation of sperm release
Summary
We are investigating the process of sperm release to aid in the discovery of new, non-hormone-based contraceptives and to better understand some forms of male infertility.
Description
After sperm have completed their development within the testis they are released from the supporting Sertoli cells and are transported to the epididymis. This process of release from the Sertoli cell is known as spermiation and while it is well described morphologically, the molecular events controlling spermiation are unknown. Spermiation is a key factor in determining sperm counts and when spermiation failure occurs, sperm are not released from the Sertoli cell but are instead retained and phagocytosed.
We have found that spermiation failure occurs when hormone-based contraceptives are given to male rodents, monkeys and humans. Contraceptives that target spermiation would likely be rapid acting and effective and therefore elucidating the molecular pathways that control spermiation are of considerable clinical significance. This research is also relevant to developing treatments for conditions of male infertility, such as some forms of non-obstructive azoospermia.
We use in vivo rodent models in which spermiation is suppressed to discover which genes, proteins and molecular pathways are changed during spermiation failure. We use genome microarrays and proteomic approaches (Western blotting, DIGE and Mass Spectrometry) to discover changes in genes and proteins and investigate the localisation of spermiation-associated proteins using immunocytochemistry. We also use seminiferous tubule cultures to manipulate sperm release in vitro.
Funding
Bayer Schering Pharma
- National Health and Medical Research Council
Outcomes
Description of spermiation as a key target for hormone-based contraceptives in men
Description of a novel adhesion junction that is present at the site of spermiation
Selected Publications
Beardsley A, Robertson DM, O'Donnell L (2006) A complex containing alpha6/beta1 integrin and phosphorylated FAK between Sertoli cells and elongated spermatids during spermatid release from the seminiferous epithelium. J Endocrinology 190:759-70
Matthiesson KL, McLachlan RI, O'Donnell L, Frydenberg M, Robertson DM, Stanton PG, Meachem SJ. (2006) The relative roles of FSH and LH in maintaining spermatogonial populations and spermiation in normal men. J Clin Endocrinol Metab 91:3962-3969
Matthiesson KL, Stanton PG, O'Donnell L, Meachem SJ, Amory JK, Berger R, Bremner WJ, and McLachlan RI. (2005) Effects of testosterone and levonorgestrel combined with a 5 alpha reductase inhibitor or GnRH antagonist on spermatogenesis and intratesticular steroid levels in normal men. J Clin Endocrinol Metab 90:5647-5655
Beardsley A, O'Donnell L. (2003) Characterization of normal spermiation and spermiation failure induced by hormone suppression in adult rats. Biol Reprod. 68:1299-1307
McLachlan RI, O'Donnell L, Stanton PG, Balourdos G, Frydenberg M, de Kretser DM, Robertson DM. (2002) Effects of testosterone plus medroxyprogesterone acetate on semen quality, reproductive hormones and germ cell populations in normal young men. J Clinical Endocrinol Metab 87: 546-556
O'Donnell L, Narula A, Balourdos G, Gu Y, Wreford NG, Robertson DM, Bremner WJ, McLachlan RI. (2001) Impairment of spermatogonial development and spermiation after testosterone-induced gonadotropin suppression in adult monkeys (Macaca fascicularis). J Clinical Endocrinol Metab 86:1814-1822
Saito K, O'Donnell L, McLachlan RI, Robertson DM (2000) Spermiation failure is a major contributor to early spermatogenic suppression caused by hormone withdrawal in adult rats. Endocrinology 141:2779-2785