002.Sertoli cell terminal differentiation: doing a 'U' turn on a one way street

2005 ◽  
Vol 17 (9) ◽  
pp. 62
Author(s):  
S. J. Meachem

The concept of terminal differentiation of Sertoli cells has been challenged and this new information has important implications for male fertility. The mammalian Sertoli cell has two distinct functions: (i) formation of the seminiferous cords and (ii) provision of nutritional and structural support to the developing germ cells. For these to occur successfully, Sertoli cells must undergo numerous maturational changes between foetal and adult life, the main switches occur around the onset of puberty, coincident with the rise in serum gonadotrophins. These switches include the loss of proliferative activity and the formation of the blood testis barrier. Follicle stimulating hormone (FSH) plays a key role in supporting Sertoli cell proliferation in early postnatal life and thus is critical in establishing sperm output in adulthood. After puberty, the size of the Sertoli cell population is considered to be stable and unmodifiable by hormones. This accepted view has been contested as data shows that the size of the adult Sertoli cell population is modifiable by hormone suppression, and that Sertoli cells can regain proliferative activity when stimulated by FSH in the Djungarian hamster1. The molecular mechanism(s) by which Sertoli cells re-enter proliferation are not known in this model however a study demonstrated that helix-loop-inhibitor of differentiation proteins can induce terminally differentiated Sertoli cells to re-enter the cell cycle and proliferate2. Thyroid hormone and testosterone may be involved in the cessation of Sertoli cell proliferation. Gonadotrophin suppression in the adult Djungarian hamster also results in the disruption of the blood testis barrier and spatial organisation of the inter Sertoli cell tight junction proteins and as a consequence the loss of all germ cells that reside inside the blood testis barrier. FSH restores the organisation of these tight junction proteins, which is associated with the appearance of more mature germ cells. It is expected that the integrity of the blood testis barrier is also re-established. It is suggested that this demonstrated plasticity of the adult Sertoli cell may be relevant in clinical settings, particularly to some types of infertility and testicular malignancies where Sertoli cells have failed to undergo these important maturational switches. (1)Chaudhary et al. (2005) Biol. Reprod. 72, 1205. (2)Meachem et al. (2005) Biol. Reprod. 72, 1187.

2005 ◽  
Vol 17 (9) ◽  
pp. 133
Author(s):  
G. A. Tarulli ◽  
P. G. Stanton ◽  
S. J. Meachem

Sperm production relies on nutritional and structural support from Sertoli cells. Sertoli cells undergo maturational changes (e.g. cessation of proliferation and formation of the blood–testis barrier) around the onset of puberty in higher mammals1 and maturational failure has been associated with some infertility syndromes and testicular malignancies2. The Sertoli cell population is considered to be stable and unmodifiable by hormones after puberty in mammals, although recent data using the adult Djungarian hamster showed that Sertoli cell numbers decreased by 35% in the absence of serum gonadotrophins, and returned to control levels by short-term replacement of follicle stimulating hormone (FSH)3. Therefore, the aims of this study were to (i) quantify the proliferative activity of Sertoli cells in the hormonally manipulated Djungarian hamster, and (ii) examine the localisation of several tight junction proteins as markers of the blood–testis barrier. Long day (LD) photoperiod (16L : 8D) adult hamsters were exposed to short day (SD) photoperiod (8L : 16D) for 11 weeks to suppress gonadotrophins and then received FSH for up to 10 days. Sertoli cell proliferation was assessed immunohistochemically by the colocalisation of GATA-4 and PCNA, and quantified by stereology. Tight junction proteins (occludin and ZO-1) were colocalised using confocal microscopy. Sertoli cell proliferation in both the LD and SD controls was minimal; however, in response to FSH treatment proliferation was upregulated within 4 days compared with SD controls (98% v. 2%, P < 0.001, respectively). Tight junction proteins colocalised at the blood–testis barrier in LD hamsters, but were disorganised within the Sertoli cell cytoplasm in SD animals. FSH treatment restores colocalisation in a time-dependent manner. It is concluded that FSH contributes to the regulation of Sertoli cell proliferation and tight junction formation in the adult Djungarian hamster. This data provides definitive evidence that the adult Sertoli cell population in this model is modifiable by hormones. (1)Meachem et al. (2005). Biol Reprod 72, 1187.(2)Allan et al. (2004). Endocrinol 145, 1587.(3)Russell and Peterson (1985). Int Rev Cytol 94, 177.


2018 ◽  
Vol 121 ◽  
pp. 42-52 ◽  
Author(s):  
Wei-Rong Yang ◽  
Ting-Ting Liao ◽  
Zi-Qiang Bao ◽  
Cai-Quan Zhou ◽  
Hong-Yan Luo ◽  
...  

1990 ◽  
Vol 2 (3) ◽  
pp. 225 ◽  
Author(s):  
Kretser DM de

The interactions between the Sertoli cells and germ cells are progressively becoming an important part of testicular physiology. This paper explores the cytological basis for these interactions, detailing the cyclic changes in the Sertoli cells in concert with the stages of the seminiferous cycle and the nature of the blood-testis barrier. These cytological changes are correlated with a number of variations in the function of Sertoli cells. The mechanisms by which germ cells and Sertoli cells interact are explored and can be divided into those using cell-to-cell contact and others utilizing paracrine factors.


2010 ◽  
Vol 41 (2) ◽  
pp. 117-125 ◽  
Author(s):  
Stelios F. Assimakopoulos ◽  
Athanassios C. Tsamandas ◽  
Emanuel Louvros ◽  
Constantine E. Vagianos ◽  
Vassiliki N. Nikolopoulou ◽  
...  

Author(s):  
Rachel L Gewiss ◽  
Nathan C Law ◽  
Aileen R Helsel ◽  
Eric A Shelden ◽  
Michael D Griswold

Abstract Sertoli cells are a critical component of the testis environment for their role in maintaining seminiferous tubule structure, establishing the blood-testis barrier, and nourishing maturing germ cells in a specialized niche. This study sought to uncover how Sertoli cells are regulated in the testis environment via germ cell crosstalk in the mouse. We found two major clusters of Sertoli cells as defined by their transcriptomes in Stages VII–VIII of the seminiferous epithelium and a cluster for all other stages. Additionally, we examined transcriptomes of germ cell-deficient testes and found that these existed in a state independent of either of the germ cell-sufficient clusters. Altogether, we highlight two main transcriptional states of Sertoli cells in an unperturbed testis environment, and a germ cell-deficient environment does not allow normal Sertoli cell transcriptome cycling and results in a state unique from either of those seen in Sertoli cells from a germ cell-sufficient environment.


2020 ◽  
Vol 103 (4) ◽  
pp. 880-891
Author(s):  
Phillip A Thomas ◽  
Eric D Schafler ◽  
Sophie E Ruff ◽  
Maud Voisin ◽  
Susan Ha ◽  
...  

Abstract Spermatogenesis is a complex process that establishes male fertility and involves proper communication between the germline (spermatozoa) and the somatic tissue (Sertoli cells). Many factors that are important for spermatozoa production are also required for Sertoli cell function. Recently, we showed that the transcriptional cofactor ubiquitously expressed transcript (UXT) encodes a protein that is essential in germ cells for spermatogenesis and fertility. However, the role of UXT within Sertoli cells and how it affects Sertoli cell function was still unclear. Here we describe a novel role for UXT in the Sertoli cell’s ability to support spermatogenesis. We find that the conditional deletion of Uxt in Sertoli cells results in smaller testis size and weight, which coincided with a loss of germ cells in a subset of seminiferous tubules. In addition, the deletion of Uxt has no impact on Sertoli cell abundance or maturity, as they express markers of mature Sertoli cells. Gene expression analysis reveals that the deletion of Uxt in Sertoli cells reduces the transcription of genes involved in the tight junctions of the blood–testis barrier (BTB). Furthermore, tracer experiments and electron microscopy reveal that the BTB is permeable in UXT KO animals. These findings broaden our understanding of UXT’s role in Sertoli cells and its contribution to the structural integrity of the BTB.


2014 ◽  
Vol 307 (7) ◽  
pp. E553-E562 ◽  
Author(s):  
Xiang Xiao ◽  
Dolores D. Mruk ◽  
Elissa W. P. Wong ◽  
Will M. Lee ◽  
Daishu Han ◽  
...  

The blood-testis barrier (BTB) is one of the tightest blood-tissue barriers in the mammalian body. However, it undergoes cyclic restructuring during the epithelial cycle of spermatogenesis in which the “old” BTB located above the preleptotene spermatocytes being transported across the immunological barrier is “disassembled,” whereas the “new” BTB found behind these germ cells is rapidly “reassembled,” i.e., mediated by endocytic vesicle-mediated protein trafficking events. Thus, the immunological barrier is maintained when preleptotene spermatocytes connected in clones via intercellular bridges are transported across the BTB. Yet the underlying mechanism(s) in particular the involving regulatory molecules that coordinate these events remains unknown. We hypothesized that c-Src and c-Yes might work in contrasting roles in endocytic vesicle-mediated trafficking, serving as molecular switches, to effectively disassemble and reassemble the old and the new BTB, respectively, to facilitate preleptotene spermatocyte transport across the BTB. Following siRNA-mediated specific knockdown of c-Src or c-Yes in Sertoli cells, we utilized biochemical assays to assess the changes in protein endocytosis, recycling, degradation and phagocytosis. c-Yes was found to promote endocytosed integral membrane BTB proteins to the pathway of transcytosis and recycling so that internalized proteins could be effectively used to assemble new BTB from the disassembling old BTB, whereas c-Src promotes endocytosed Sertoli cell BTB proteins to endosome-mediated protein degradation for the degeneration of the old BTB. By using fluorescence beads mimicking apoptotic germ cells, Sertoli cells were found to engulf beads via c-Src-mediated phagocytosis. A hypothetical model that serves as the framework for future investigation is thus proposed.


Sign in / Sign up

Export Citation Format

Share Document