Regulation of somatic and germ cells in the testis

Summary

This research effort is focused on the 2 main cell types that are essential for male fertility; the somatic Sertoli cell and developing sperm cells. These studies are exploring the genes and the hormones that control these cell types which ensure maximal sperm output. This work uses well characterised models and clinical samples of infertility to identify mechanisms of control in the healthy and diseased testis.

Description

One in twenty men suffer are affected by infertility conditions. However, only in a minority of men is a cause found or is a specific treatment available. For the majority it appears that genetic, environmental and hormonal factors combine and lead to the production of inadequate sperm number, or sperm of poor quality. Understanding the basis of this problem will improve diagnostic and treatment options, with the hope that natural fertility may be restored.

This research is looking at the hormonal factors that determine sperm production which normally occurs over a 2 month period in the lining of the sperm-producing tubules of the testis. Immature sperm cells are enveloped in a larger cell, called the somtatic Sertoli cell, which nurtures their development. Proper communication between Sertoli and sperm cells is critical in allowing their normal development.

This research is looking at the communication bridges between them in the healthy and diseased testis. A hormone signal (called FSH) from the brain acts directly on the Sertoli cell along with testosterone which is made in large amounts in the testis.

This research is looking at the way in which FSH and testosterone work to encourage sperm cell development and prevent their premature death.

For a sperm cell to develop properly they not only need hormones but a fully functional adult Sertoli cell population. This population becomes adult at puberty and is thought to remain that way throughout life.

Exciting new findings show that in infertile models and human samples of infertility that the Sertoli cell population is not mature (it displays features of an immature Sertoli cell population, similar to the one seen before puberty) and I am eager to determine whether an immature Sertoli cell population is a cause or an effect of impaired sperm cell development.

A related research project is endeavouring to discover the best way to inhibit sperm production as a method of male contraception. This approach involves giving men testosterone and another sex hormone, called progestin, in order to turn off the brain hormones that drive sperm production. The research has found these treatments work in 2 ways to lower the sperm count toward zero. The first is to reduce the development of the testicular stem cells entering the pathway of sperm production. The second is to stop mature sperm being released from the Sertoli cells.

Funding

National Health and Medical Research Council

Outcomes

Demonstration that the adult Sertoli cell differentiation status is in fact programmable by various endocrinological cues
Identified some of the molecular pathways that underpin germ cell survival

Selected Publications

Ruwanpura S, McLachlan R, Matthiesson K, Meachem S (2008) Gonadotrophins regulate germ cell survival, not proliferation, in normal men. Human Reprod 23:403-411

Ruwanpura S, McLachlan R, Stanton P, Meachem S (2008). FSH effects spermatogonial survival, by regulating the intrinsic apoptotic pathway in adult rats. Biol Reprod. 78:705-713

Meachem S, Kavallaris M, Hulett M, West C, Pitt R, Chesters J, Laffan W, Boreham P, Khachigian L (2008) Perceptions in Health and Medical Research Careers: The Australian Society for Medical Research Workforce Survey. Medical Journal of Australia. 188:9:520-524

Tarulli GA, Stanton PG, Lerchl A, Meachem SJ (2006) Adult Sertoli cells are not terminally differentiated in the Djungarian hamster: Effect of FSH on proliferation and junction protein organization. Biol Reprod. 74:798-806

O'Donnell L, Meachem SJ, Stanton PG and McLachlan RI. (2006) The endocrine regulation of spermatogenesis. In: Neill JD (ed), Knobil and Neill's Physiology of Reproduction (3rd ed). Elsevier, San Diego CA. pp. 1017-1069

Matthiesson KL, McLachlan RI, O'Donnell L, Frydenberg M, Robertson DM, Stanton PG, Meachem SJ (2006) The relative roles of follicle-stimulating hormone and luteinizing hormone in maintaining spermatogonial maturation and spermiation in normal men. J Clin Endocrinol Metab. 91:3962-3969

Loveland KL, Hogarth C, Mendis S, Huebner A, Ly J, Itman C, Meachem S, Brown CW, Jans DA (2005) Drivers of germ cell maturation. Ann NY Acad Sci 1061: 173-182

Meachem SJ, Stanton, PG, Schlatt (2005) Follicle stimulating hormone (FSH) regulates both Sertoli cell and spermatogonial populations in the adult photoinihibited Djungarian hamster testis. Biol Reprod. 72:1187-1193

Meachem SJ, Ruwanpura SM, Ziolkowski J, Ague JM, Skinner MK, Loveland KL (2005) Developmentally distinct in vivo effects of FSH on proliferation and apoptosis during testis maturation. J Endocrinol. 186:429-446

PHI Research Team