Regulation of Sertoli Cell junctions

Summary

We are investigating the ways in which hormones control junctions between cells in the testis, as these are potential sites of action of male hormonal contraception.

Description

The regulation of cell junctions (tight junctions, adhesion junctions) in the testis is critical for the process of spermatogenesis (sperm production). Suppression of the major endocrine regulators of spermatogenesis, FSH and androgens, disrupts intercellular adhesion, particularly between developing germ cells and the somatic Sertoli cells.

A key focus of our laboratory is the developmental step called spermiation which includes the final release of sperm, where we have shown that suppression of hormone action prevents sperm release in rats, monkeys and men. We are utilising genomic and proteomic approaches to study the adhesion-related genes between Sertoli cells and developing spermatids in order to identify the regulatory pathways by which Sertoli cell-germ cell adhesion is regulated (see Current Research: Regulation of Sperm Release).

We are also investigating the blood-testis barrier, which is a permeability barrier functioning to sequester germ cells undergoing meiotic and post-meiotic differentiation from the vascular environment. Tight junctions found between Sertoli cells are the major component of this barrier in the adult testis. Sertoli cell tight junctions are required for fertility and it is well known that their disruption leads to germ cell atresia and cessation of spermatogenesis.

We use a combination of in vitro and in vivo models of hormone manipulation to modulate Sertoli cell tight junctions, and use real time PCR, Western and proteomic approaches, as well as immunohistochemistry and tracer permeability assays to study the components of these junctions and their regulatory pathways.

Funding

National Health and Medical Research Council

Outcomes

Description of androgen-regulated tight junction-associated proteins

Description of Sertoli cell tight junctions in seasonally breeding hamsters

Selected Publications

Nicholls PK, Harrison CA, Gilchrist RB, Farnworth PG & Stanton PG (2009). Growth differentiation factor 9 (GDF9) is a germ-cell regulator of Sertoli cell function. Endocrinology 150:2481-2490

Sluka P, O'Donnell L, McLachlan RI & Stanton PG (2008) Application of laser-capture microdissection to the analysis of gene expression in the testis. Progress In Histochemistry and Cytochemistry 42:173-201

Tarulli GA, Meachem SJ, Schlatt S & Stanton PG (2008) Regulation of testicular tight junctions by gonadotrophins in the adult Djungarian hamster in vivo. Reproduction 135: 867-877

Kaitu'u-Lino TJ, Sluka P, Foo CFH & Stanton PG (2007) Claudin-11 expression and localisation is regulated by androgens in rat Sertoli cells in vitro. Reproduction 133:1169-1179

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

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

Sluka P, O'Donnell L, Bartles JR & Stanton PG (2006) FSH regulates the formation of adherens junctions and ectoplasmic specializations between rat Sertoli cells in vitro and in vivo. J Endocrinol 189:381-395.

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

PHI Research Team