scholarly journals An overview of a Sertoli cell transplantation model to study testis morphogenesis and the role of the Sertoli cells in immune privilege

2017 ◽  
Vol 3 (3) ◽  
Author(s):  
Gurvinder Kaur ◽  
Scott Vadala ◽  
Jannette M. Dufour
Author(s):  
N. N. Skaletskiy ◽  
G. N. Skaletskaya

Due to complications caused by the inevitable use of immunosuppressive drugs in organ and cell transplantation, the use of natural mechanisms of immunological tolerance identified in animal and human organisms arouses interest. It has long been known that there are certain areas in them, including the testis, where immune reactions are virtually impossible. Our review focuses on the role of Sertoli cells that provide testicular immune privilege. Methods of isolation and cultivation of Sertoli cells are described and their potentials in biology and medicine are discussed.


It has long been assumed that the mammalian Y chromosome either encodes, or controls the production of, a diffusible testis-determining molecule, exposure of the embryonic gonad to this molecule being all that is required to divert it along the testicular pathway. My recent finding that Sertoli cells in XX ↔ XY chimeric mouse testes are exclusively XY has led me to propose a new model in which the Y acts cell-autonomously to bring about Sertoli-cell differentiation. I have suggested that all other aspects of foetal testicular development are triggered by the Sertoli cells without further Y-chromosome involvement. This model thus equates mammalian sex determination with Sertoli-cell determination. Examples of natural and experimentally induced sex reversal are discussed in the context of this model.


1977 ◽  
Vol 75 (2) ◽  
pp. 209-219 ◽  
Author(s):  
F. H. DE JONG ◽  
R. M. SHARPE

Peripheral concentrations of FSH in the male rat seem to be regulated in part by a protein hormone, inhibin, which originates from the testes. In an attempt to ascertain which type of testicular cell secretes inhibin, groups of male rats were irradiated prenatally or on days 4, 6 or 8 of postnatal life, and killed at 21, 51 or 81 days of age together with castrated and intact controls. The concentrations of FSH and LH in the pituitary gland, and FSH, LH and testosterone in the plasma were estimated for each animal, and the numbers of each class of intratubular cell in the testes were calculated. Rats irradiated neonatally had fewer Sertoli cells than controls at all ages studied, while the numbers of Sertoli cells in rats irradiated prenatally were higher than those in controls on day 21. The number of spermatogenic cells was usually decreased in rats irradiated postnatally. In the rats irradiated prenatally normal numbers of spermatogenic cells were found at day 51. Numbers of spermatogenic cells were significantly correlated with the number of Sertoli cells at the ages of 51 and 81 days. The concentration of FSH in the plasma usually increased in the postnatally irradiated animals on days 21 and 51, but not on day 81; prenatal irradiation did not result in altered levels of FSH at any age. Peripheral levels of LH and testosterone were not affected by irradiation. The concentration of FSH in the plasma was negatively correlated with the number of Sertoli cells in all age groups, whereas significant correlations between the level of FSH and the number of spermatogenic cells were only found at days 51 and 81. It is concluded from these data that the Sertoli cell is the most likely source of inhibin.


1995 ◽  
Vol 145 (2) ◽  
pp. 355-362 ◽  
Author(s):  
S Palmero ◽  
M Prati ◽  
F Bolla ◽  
E Fugassa

Abstract The addition of physiological concentrations (1 nm) of tri-iodothyronine (T3) to the culture medium of Sertoli cells from prepubertal (8-day-old) rats stimulated both protein synthesis (+55%) and lactate (+50%) production, while it inhibited DNA synthesis (−30/35%) and aromatase activity (−45/50%); insignificant T3-dependent effects were observed in cultured Sertoli cells from midpubertal (28-day-old) rats. These data suggest an age-dependent role for thyroid hormone in promoting and maintaining Sertoli cell differentiation at puberty; moreover, the hormone is involved in the regulation of Sertoli cell proliferation. The present study validates the role of Sertoli cells as a specific target for T3 action at the testis level; it also demonstrates the existence of an early and critical direct influence of thyroid hormone on Sertoli cell proliferation and functional maturation. Journal of Endocrinology (1995) 145, 355–362


2002 ◽  
Vol 174 (2) ◽  
pp. 195-204 ◽  
Author(s):  
SB Meroni ◽  
MF Riera ◽  
EH Pellizzari ◽  
SB Cigorraga

The FSH molecular mechanism of action is best recognized for its stimulation of the adenylyl cyclase/cAMP pathway via activation of a G protein. Recently, links between cAMP, phosphatidylinositol 3-kinase (PI3K) and protein kinase B (PKB) signaling pathways in thyroid and granulosa cells have been observed. The aim of this study was to investigate the possible role of the PI3K/PKB pathway in FSH regulation of Sertoli cell function. Twenty-day-old rat Sertoli cell cultures were used. An increase in phosphorylated PKB (P-PKB) levels in response to FSH and dibutyryl-cAMP was observed. These increments in P-PKB levels were not observed in the presence of two PI3K inhibitors, wortmannin and Ly 294002. Inhibition of protein kinase A (PKA) by H89 did not decrease FSH stimulation of P-PKB levels. Taken together, these results indicate that FSH increases P-PKB levels in a PI3K-dependent and PKA-independent manner in rat Sertoli cells. In addition, wortmannin partially inhibited the ability of FSH to stimulate two well-known parameters of Sertoli cell function - transferrin secretion and lactate production - at doses equal to or lower than 0.1 microM. Related to lactate production, a decrease in FSH stimulation of lactate dehydrogenase activity and of basal and FSH-stimulated glucose uptake was observed in the presence of wortmannin. These metabolic changes were in most cases accompanied by changes in the levels of P-PKB. Altogether, these results suggest a meaningful role of the PI3K/PKB pathway in the mechanism of action of FSH in rat Sertoli cells.


2021 ◽  
Vol 12 ◽  
Author(s):  
Wasim Shah ◽  
Ranjha Khan ◽  
Basit Shah ◽  
Asad Khan ◽  
Sobia Dil ◽  
...  

Sustaining and maintaining the intricate process of spermatogenesis is liable upon hormones and growth factors acting through endocrine and paracrine pathways. The Sertoli cells (SCs) are the major somatic cells present in the seminiferous tubules and are considered to be the main regulators of spermatogenesis. As each Sertoli cell supports a specific number of germ cells, thus, the final number of Sertoli cells determines the sperm production capacity. Similarly, sex hormones are also major regulators of spermatogenesis and they can determine the proliferation of Sertoli cells. In the present review, we have critically and comprehensively discussed the role of sex hormones and some other factors that are involved in Sertoli cell proliferation, differentiation and maturation. Furthermore, we have also presented a model of Sertoli cell development based upon the recent advancement in the field of reproduction. Hence, our review article provides a general overview regarding the sex hormonal pathways governing Sertoli cell proliferation and development.


2007 ◽  
Vol 194 (3) ◽  
pp. 557-568 ◽  
Author(s):  
P Froment ◽  
M Vigier ◽  
D Nègre ◽  
I Fontaine ◽  
J Beghelli ◽  
...  

IGF-I regulates pituitaryand gonadal functions, and is pivotal for sexual development and fertility in mammalian species. To better understand the function of autocrine IGF-I in Sertoli cell physiology, we established a system for Cre-mediated conditional inactivation of the IGF-I receptor (IGF-IR) in cultured Sertoli cells. We show here that loss of IGF-IR decreased the number of viable Sertoli cells as a consequence of diminished Sertoli cell proliferation and increased Sertoli cell death. Furthermore, the lack of IGF-IR altered the morphology of cultured Sertoli cells and decreased lactate and transferrin secretions. Collectively, our data indicate that autocrine IGF-I contributes significantly to Sertoli cell homeostasis. The described in vitro system for loss-of-function analysis of the IGF-IR can be readily transposed to study the role of other intratesticular growth factors involved in spermatogenesis.


Endocrinology ◽  
2003 ◽  
Vol 144 (2) ◽  
pp. 474-483 ◽  
Author(s):  
Jeremy J. Buzzard ◽  
Paul G. Farnworth ◽  
David M. de Kretser ◽  
Anne E. O’Connor ◽  
Nigel G. Wreford ◽  
...  

We have used cultures of highly purified, proliferating rat Sertoli cells collected from d 3, 6, and 9 rat pups to investigate the role of activin A on Sertoli cell division. These studies demonstrate that activin A acts directly on d 6 and 9, but not d 3, Sertoli cells to induce proliferation, both alone and synergistically with FSH. In addition to stimulating proliferation, activin A induces secretion of inhibins A and B as determined by specific ELISAs. We demonstrate that the synergy between activin A and FSH is not due to local actions of secreted inhibin or follistatin. We have used real-time fluorometric RT-PCR to demonstrate that activin regulates expression of activin receptor and follistatin mRNA by Sertoli cells. Saturation binding studies using 125I-activin A indicate that synergy between activin and FSH may be due to increased numbers of activin receptors on the Sertoli cell. Finally, we show that activin A was secreted at high levels by cultured peritubular cells but was undetectable in high purity proliferating Sertoli cell cultures, suggesting that activin A functions as a paracrine factor during postnatal testis development.


2004 ◽  
Vol 16 (9) ◽  
pp. 127
Author(s):  
A. J. Beardsley ◽  
D. M. Robertson ◽  
L. O'Donnell

Spermiation is the final step of spermatogenesis (sperm production) where mature spermatids are released from the somatic Sertoli cells. Spermiation is hormone sensitive; testosterone (T) and FSH withdrawal causes a disruption to the disengagement of spermatids, which are instead retained by Sertoli cells. The mechanisms involved with spermatid release and retention are not understood. We showed previously that an unknown adhesion junction containing β1-integrin persisted on retained spermatids suggesting that a defect in this adhesion complex at disengagement may underlie spermiation failure. The aim of this study is to identify the α-integrin dimerised with β1-integrin and investigate the role of phosphorylated FAK, a kinase that is involved with integrin-mediated cell adhesion, during spermiation and spermiation failure. Four adult Sprague-Dawley rats received T and oestradiol implants and FSH antibody for 7A days to suppress testicular T and FSH and induce spermiation failure. Using immunohistochemistry, α6-integrin (but not α4-integrin) and FAK-Tyr397 were localised on the Sertoli cell plasma membrane adjacent to mature spermatids. This localisation was observed until the point of spermatid release and remained on the Sertoli cell that surrounded retained spermatids after hormone suppression. A similar localisation has been previously observed with β1-integrin, suggesting that all three form a complex at the site of disengagement. To look at the function of FAK-Tyr397, comparative Western blot analysis is currently being undertaken on seminiferous tubules specific for spermiation from control and treated animals. Preliminary studies suggest that FAK-Tyr397 remains phosphorylated during spermiation failure, suggesting that FAK dephosphorylation may be important for the function of spermatid-associated adhesion complexes, as has been demonstrated in other adhesion systems. In conclusion, α6β1-integrin/FAK-containing adhesion complexes are associated with spermatids during spermiation, and the function of such complexes are likely to be perturbed during spermiation failure.


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