FSH regulates the formation of adherens junctions and ectoplasmic specialisations between rat Sertoli cells in vitro and in vivo

Abstract

Spermatogenesis is dependent on the ability of Sertoli cells to form mature junctions that maintain a unique environment within the seminiferous epithelium. Adjacent Sertoli cells form a junctional complex that includes classical adherens junctions and testis-specific ectoplasmic specialisations (ES). The regulation of inter-Sertoli cell junctions by the two main endocrine regulators of spermatogenesis, FSH and testosterone, is unclear. This study aimed to investigate the effects of FSH and testosterone on interSertoli cell adherens junctions (as determined by immunolocalisation of cadherin, catenin and actin) and ES junctions (as determined by immunolocalisation of espin, actin and vinculin) in cultured immature Sertoli cells and GnRH-immunised adult rat testes given FSH or testosterone replacement in vivo. When hormones were absent in vitro, adherens junctions formed as discrete puncta between interdigitating, finger-like projections of Sertoli cells, but ES junctions were not present. The adherens junction puncta included actin filaments that were oriented perpendicularly to the Sertoli cell plasma membrane, but were not associated with the intermediate filament protein vimentin. When FSH was added in vitro, ES junctions formed, and adjacent adherens junction puncta fused into extensive adherens junction belts. After hormone suppression in vivo, ES junctions were absent, while FSH replacement restored ES junctions, as confirmed by electron microscopy and confocal analysis of ES-associated proteins. Testosterone alone did not affect adherens junctions or ES in vitro or in vivo. We conclude that FSH can regulate the formation of ES junctions and stimulate the organisation and orientation of extensive adherens junctions in Sertoli cells.

Testicular apoptosis after dietary zinc deficiency: Ultrastructural and TUNEL studies

“…The highly coordinated nature of spermatogenesis requires intimate functional and junctional communication between Sertoli and germ cells [Sluka et al 2006]. In the present study, the ovoid nucleus of Sertoli cells in the 2 and 4 w ZC and PF groups was characterized by a deep indentation with a well-defined dense nucleolus.…”

Hormonal regulation of male germ cell development

“…However, acute FSH suppression has led to a reduction in pachytene spermatocyte numbers at stage VII in the presence of normal levels of androgens (Meachem et al 1999), suggesting a direct effect of FSH. FSH plays a role in spermiogenesis (McLachlan et al 1995, Meachem et al 1998 perhaps by regulating adhesion and junctions between Sertoli cells and spermatids (Muffly et al 1994, Sluka et al 2006. Our laboratory has identified that sperm fail to be released after passive FSH immunization (Saito et al 2000), indicating a role of FSH in spermiation process.…”

“…Synergy between FSH and testosterone is observed at spermatocyte development, wherein only partial maintenance or restoration of meiosis is achieved by individual hormone suppression or replacement, while combined exposure is much more effective (reviewed in McLachlan et al (2002a)). There are few studies to suggest that testosterone together with FSH promotes spermiogenesis by promoting adhesion of round spermatids to Sertoli cells , Sluka et al 2006. FSH and testosterone synergy is mainly demonstrated in spermiation.…”

“…The highly coordinated nature of spermatogenesis requires intimate functional and junctional communications between Sertoli and germ cells (Kierszenbaum & Tres 2004, reviewed in Mruk & Cheng (2004 and Sluka et al (2006)). It is generally accepted that germ cells do not contain receptors for hormones; thus, these endocrine factors exert their biological effects on spermatogenesis via the receptors located in or on the plasma membrane of Sertoli cells (Parvinen 1982).…”

Molecular mechanisms by which hormones and cytokines regulate cell junction dynamics in the testis

“…An in vitro study has confirmed that FSH is important to stimulate the relocation of ES proteins such as epsin and in the presence of FSH, cultured Sertoli cells are capable of forming not only the classical AJs, but also the AJ belts and the testis-specific ES which contains actin and epsin (Sluka et al 2006). Other than ES proteins, FSH also regulates the tight junction proteins such as coxsackievirus and adenovirus receptor (CAR) and claudin-11 in the testis (Mirza et al 2007).…”