Molecular mechanisms involved in Sertoli cell adaptation to glucose deprivation

2009 ◽  
Vol 297 (4) ◽  
pp. E907-E914 ◽  
Author(s):  
María F. Riera ◽  
María N. Galardo ◽  
Eliana H. Pellizzari ◽  
Silvina B. Meroni ◽  
Selva B. Cigorraga
Keyword(s):  
Germ Cell ◽  
Glucose Uptake ◽  
Sertoli Cell ◽  
Sertoli Cells ◽  
Molecular Mechanisms ◽  
Lactate Concentration ◽  
Glucose Deprivation ◽  
Cell Development ◽  
Germ Cell Development ◽  
Glucose Levels

Sertoli cells provide the physical support and the necessary environment for germ cell development. Among the products secreted by Sertoli cells, lactate, the preferred energy substrate for spermatocytes and spermatids, is present. Considering the essential role of lactate on germ cell metabolism, it is supposed that Sertoli cells must ensure its production even in adverse conditions, such as those that would result from a decrease in glucose levels in the extracellular milieu. The aim of the present study was to investigate 1) a possible effect of glucose deprivation on glucose uptake and on the expression of glucose transporters in rat Sertoli cells and 2) the participation of different signal transduction pathways in the above-mentioned regulation. Results obtained show that decreasing glucose levels in Sertoli cell culture medium provokes 1) an increase in glucose uptake accompanied by only a slight decrease in lactate production, 2) an increase in GLUT1 and a decrease in GLUT3 expression, and 3) an activation of AMP-activated protein kinase (AMPK)-, phosphatidylinositol 3-kinase (PI3K)/PKB-, and p38 MAPK-dependent pathways. Additionally, by using specific inhibitors of these pathways, a possible participation of AMPK- and p38MAPK-dependent pathways in the regulation of glucose uptake and GLUT1 expression is shown. These results suggest that Sertoli cells adapt to conditions of glucose deprivation to ensure an adequate lactate concentration in the microenvironment where germ cell development occurs.

Transgenic mutant D567G but not wild-type human FSH receptor overexpression provides FSH-independent and promiscuous glycoprotein hormone Sertoli cell signaling

2009 ◽  
Vol 296 (5) ◽  
pp. E1022-E1028 ◽  
Author(s):  
Charles M. Allan ◽  
Patrick Lim ◽  
Mathew Robson ◽  
Jenny Spaliviero ◽  
David J. Handelsman
Keyword(s):  
Germ Cell ◽  
Sertoli Cell ◽  
Sertoli Cells ◽  
Cell Development ◽  
Fsh Receptor ◽  
Wild Type ◽  
Glycoprotein Hormone ◽  
Germ Cell Development ◽  
Camp Levels

We have characterized the in vivo actions of human wild-type FSH receptor (FSHR) overexpressed in Sertoli cells of transgenic (Tg) mice ( TgFSHRwt) compared with transgenic overexpression of the human activated mutant FSHR*D567G ( TgFSHR*D567G). Testicular TgFSHRwt expression significantly elevated specific FSH binding (>2-fold, P < 0.01) relative to nontransgenic testes, similar to increased FSH binding in TgFSHR*D567G testes. Isolated TgFSHRwt Sertoli cells exhibited higher FSH-stimulated cAMP levels compared with non- Tg or TgFSHR*D567G cells but did not display the elevated FSH-independent basal cAMP levels found in TgFSHR*D567G Sertoli cells. Furthermore, Sertoli cell overexpression of TgFSHR*D567G but not TgFSHRwt allowed promiscuous cAMP responses to human chorionic gonadotropin (300 IU/ml) and TSH (30 mIU/ml), demonstrating increased constitutive signaling and altered glycoprotein hormone specificity via the intracellular D567G substitution rather than FSHR overexpression. Despite elevating Sertoli cell FSH sensitivity, overexpression of TgFSHRwt had no detectable effect upon normal testis function and did not stimulate Sertoli and germ cell development in testes of gonadotropin-deficient hypogonadal ( hpg) mice, in contrast to the increased meiotic and postmeiotic germ cell development in TgFSHR*D567G hpg testes. Increased steroidogenic potential of TgFSHR*D567G hpg testes was demonstrated by elevated Cyp11a1 and Star expression, which was not detected in TgFSHRwt hpg testes. Androgen-regulated and Sertoli cell-specific Rhox5 gene expression was increased in TgFSHR*D567G but not TgFSHRwt hpg testes, providing evidence of elevated LH-independent androgen activity due to mutant FSHR*D567G. Hence, transgenic FSHR overexpression in Sertoli cells revealed that the D567G mutation confers autonomous signaling and steroidogenic activity in vivo as well as promiscuous glycoprotein hormone receptor activation, independently of FSHR overexpression alone.

Conditional Deletion of Pgrmc1 in Sertoli Cells Disrupts Germ Cell Development and Steroidogenesis in the Male.

2011 ◽  
Vol 85 (Suppl_1) ◽  
pp. 135-135
Author(s):  
Johnathan Broady ◽  
Jeanene DeAvila ◽  
John J. Peluso ◽  
James K. Pru ◽  
Derek J. McLean
Keyword(s):  
Germ Cell ◽  
Sertoli Cells ◽  
Cell Development ◽  
Germ Cell Development ◽  
Conditional Deletion

scholarly journals Morphological changes of Sertoli cells during the male reproductive cycle of the teleost Piaractus mesopotamicus (Holmberg, 1887)

2005 ◽  
Vol 65 (2) ◽  
pp. 241-249 ◽  
Author(s):  
C. Cruz-Landim ◽  
F. C. Abdalla ◽  
M. A. Cruz-Höfling
Keyword(s):  
Germ Cell ◽  
Sertoli Cell ◽  
Reproductive Cycle ◽  
Sertoli Cells ◽  
Morphological Changes ◽  
Cell Development ◽  
Cell Maturation ◽  
Ultrastructural Changes ◽  
Piaractus Mesopotamicus

An investigation of the histological and ultrastructural changes of Sertoli cells during the male reproductive cycle in Piaractus mesopotamicus was made. The results showed that the Sertoli cell development is closely related with germ cell maturation. Therefore, these cells may have some role in germ cell maturation during the reproductive cycle of this species, whether in forming a tissue framework for the developing spermatogenic cysts, aiding in testes reorganization for a new reproductive cycle, in addition to other possible functions discussed in the text.

220 EFFECTS OF FOLLICLE-STIMULATING HORMONE AND 6-N-PROPYL-2-THIOURACIL ON BOAR SPERMATOGENESIS

2008 ◽  
Vol 20 (1) ◽  
pp. 189
Author(s):  
J. Baldrighi ◽  
W. Averhart ◽  
M. Mello ◽  
J. Ford ◽  
L. Franca ◽  
...  
Keyword(s):  
Thyroid Hormone ◽  
Germ Cell ◽  
Sertoli Cell ◽  
Sertoli Cells ◽  
Sperm Cell ◽  
Follicle Stimulating Hormone ◽  
Cell Development ◽  
Seminiferous Tubules ◽  
Post Surgery ◽  
Stimulating Hormone

Currently, swine biotechnologies related to reproduction increase considerably. Investments are made in order to improve the reproductive rates and performance of breeding stock. Understanding the physiology of spermatogenesis will help increase sperm production and improve boar efficiency. Sertoli cells are the only somatic cells present in the seminiferous tubules. Their function is to guarantee proper sperm formation and maturation. Each Sertoli cell is responsible for nursing a finite number of spermatogonia. At puberty, Sertoli cell maturation and lumen formation have occurred within the seminiferous tubules and germ cells have proliferated rapidly followed by the onset of spermatogenesis. At least two hormones are known to play a role in Sertoli cell proliferation and maturation: follicle-stimulating hormone (FSH) and thyroid hormone. FSH secretion has been assumed to be the stimulus for proliferation. The thyroid hormone is responsible for normal postnatal growth and development. Alterations in thyroid activity have frequently been associated with changes in male reproductive functions, since hypothyroidism, induced with 6-N-propyl-2-thiouracil (PTU) soon after birth, is associated with a marked delay in sexual maturation and development. The goal of this study was to report the effect of FSH and PTU on the stages of sperm cell development of young pigs. Six piglets of 1, 7, 14, 25, and 55 days of age were castrated and their testes were sectioned to grafts of 5 mm3. The grafts were then transplanted subcutaneously into the dorsum of 12 castrated nude mice per age group. Two days post-surgery mice were randomly assigned to one of four treatment groups: control, FSH (5 IU rFSH), PTU (0.015% solution), and FSH + PTU. Following 14 days of treatment, testicular tissue pieces were allowed to grow for 2 additional weeks. Tissues were then harvested, immersion-fixed in neutral buffered formalin, and embedded in paraffin. Five-micron-thick sections were stained using hematoxylin and eosin. Slides were evaluated under light microscopy and the oldest germ cell type present in each section was recorded. Germ cell types were recorded as spermatogonium, spermatocyte, early spermatid, and late spermatid. Statistical differences between all groups were detected using paired Student t-tests. There were no differences noted between control groups and those treated with PTU or FSH alone. No effect concerning age of castration on grafts development was observed. There was a slightly significant increase (P = 0.05) in the number of spermatocytes observed in the groups treated with FSH+PTU. These data suggest that there is a potential synergistic effect of FSH and PTU on sperm cell development. Based on these results, further studies need to be performed to completely understand the effect of these two hormones on Sertoli cells.

scholarly journals 50 years of spermatogenesis: Sertoli cells and their interactions with germ cells

2018 ◽  
Vol 99 (1) ◽  
pp. 87-100 ◽  
Author(s):  
Michael D Griswold
Keyword(s):  
Germ Cell ◽  
Germ Cells ◽  
Sertoli Cells ◽  
Cultured Cells ◽  
Cell Types ◽  
Cell Development ◽  
Specific Cell ◽  
Germ Cell Development ◽  
Cell Niche ◽  
Transgenic Technologies

Abstract The complex morphology of the Sertoli cells and their interactions with germ cells has been a focus of investigators since they were first described by Enrico Sertoli. In the past 50 years, information on Sertoli cells has transcended morphology alone to become increasingly more focused on molecular questions. The goal of investigators has been to understand the role of the Sertoli cells in spermatogenesis and to apply that information to problems relating to male fertility. Sertoli cells are unique in that they are a nondividing cell population that is active for the reproductive lifetime of the animal and cyclically change morphology and gene expression. The numerous and distinctive junctional complexes and membrane specializations made by Sertoli cells provide a scaffold and environment for germ cell development. The increased focus of investigators on the molecular components and putative functions of testicular cells has resulted primarily from procedures that isolate specific cell types from the testicular milieu. Products of Sertoli cells that influence germ cell development and vice versa have been characterized from cultured cells and from the application of transgenic technologies. Germ cell transplantation has shown that the Sertoli cells respond to cues from germ cells with regard to developmental timing and has furthered a focus on spermatogenic stem cells and the stem cell niche. Very basic and universal features of spermatogenesis such as the cycle of the seminiferous epithelium and the spermatogenic wave are initiated by Sertoli cells and maintained by Sertoli-germ cell cooperation.

Retinoblastoma Protein pRb Is Required in Sertoli Cell To Support Male Germ Cell Development.

2010 ◽  
pp. P3-343-P3-343
Author(s):  
S Bourguiba ◽  
E Rotgers ◽  
A Rivero-Muller ◽  
M Nurmio ◽  
M Parvinen ◽  
...  
Keyword(s):  
Germ Cell ◽  
Sertoli Cell ◽  
Retinoblastoma Protein ◽  
Cell Development ◽  
Male Germ Cell ◽  
Germ Cell Development

scholarly journals CRISPR/Cas9-based genetic screen of SCNT-reprogramming resistant genes identifies critical genes for male germ cell development in mice

2021 ◽  
Vol 11 (1) ◽  
Author(s):  
Most Sumona Akter ◽  
Masashi Hada ◽  
Daiki Shikata ◽  
Gen Watanabe ◽  
Atsuo Ogura ◽  
...  
Keyword(s):  
Germ Cell ◽  
Germ Cells ◽  
Molecular Mechanisms ◽  
Essential Gene ◽  
Cell Development ◽  
Genetic Screen ◽  
Male Germ Cell ◽  
Specific Expression ◽  
Germ Cell Development ◽  
Resistant Genes

AbstractMale germ cells undergo complex developmental processes eventually producing spermatozoa through spermatogenesis, although the molecular mechanisms remain largely elusive. We have previously identified somatic cell nuclear transfer-reprogramming resistant genes (SRRGs) that are highly enriched for genes essential for spermatogenesis, although many of them remain uncharacterized in knockout (KO) mice. Here, we performed a CRISPR-based genetic screen using C57BL/6N mice for five uncharacterized SRRGs (Cox8c, Cox7b2, Tuba3a/3b, Faiml, and Gm773), together with meiosis essential gene Majin as a control. RT-qPCR analysis of mouse adult tissues revealed that the five selected SRRGs were exclusively expressed in testis. Analysis of single-cell RNA-seq datasets of adult testis revealed stage-specific expression (pre-, mid-, or post-meiotic expression) in testicular germ cells. Examination of testis morphology, histology, and sperm functions in CRISPR-injected KO adult males revealed that Cox7b2, Gm773, and Tuba3a/3b are required for the production of normal spermatozoa. Specifically, Cox7b2 KO mice produced poorly motile infertile spermatozoa, Gm773 KO mice produced motile spermatozoa with limited zona penetration abilities, and Tuba3a/3b KO mice completely lost germ cells at the early postnatal stages. Our genetic screen focusing on SRRGs efficiently identified critical genes for male germ cell development in mice, which also provides insights into human reproductive medicine.

TBC1D20 deficiency induces Sertoli cell apoptosis by triggering irreversible endoplasmic reticulum stress in mice

2019 ◽  
Vol 25 (12) ◽  
pp. 773-786 ◽  
Author(s):  
Wen-Lin Chang ◽  
Lina Cui ◽  
Yanli Gu ◽  
Minghua Li ◽  
Qian Ma ◽  
...  
Keyword(s):  
Endoplasmic Reticulum ◽  
Endoplasmic Reticulum Stress ◽  
Germ Cell ◽  
Sertoli Cell ◽  
Sertoli Cells ◽  
Cell Apoptosis ◽  
Molecular Mechanisms ◽  
Cycle Arrest ◽  
Proliferation And Apoptosis ◽  
Normal Spermatogenesis

Abstract Male ‘blind sterile’ mice with the causative TBC1 domain family member 20 (TBC1D20) deficiency are infertile with excessive germ cell apoptosis and spermatogenesis arrest at the spermatid stage. Sertoli cells are characterised as ‘nurse cells’ essential for normal spermatogenesis, but the role and corresponding molecular mechanisms of TBC1D20 deficiency in Sertoli cells of mice are not clear to date. In the present study, the histopathology of the testis and Sertoli cell proliferation and apoptosis were determined, and the corresponding molecular mechanisms were investigated by western blotting. Our data showed that TBC1D20 exhibits a testis-abundant expression pattern, and its expression level is positively associated with spermatogenesis. TBC1D20 is assembled in the Golgi and endoplasmic reticulum and is widely expressed by various germ cell subtypes and Sertoli cells. TBC1D20 deficiency in Sertoli cells led to an excessive apoptosis ratio and G1/S arrest. The increased apoptosis of TBC1D20-deficient Sertoli cells resulted from caspase-12 activation. TBC1D20-deficient Sertoli cells had an abnormal Golgi-endoplasmic reticulum structure, which led to endoplasmic reticulum stress, resulting in cell cycle arrest and excessive apoptosis. It suggested that TBC1D20 deficiency triggers irreversible endoplasmic reticulum stress resulting in G1/S arrest and excessive apoptosis in TBC1D20-deficient Sertoli cells, and TBC1D20 deficiency in Sertoli cells may also contribute to the infertility phenotype in ‘blind sterile’ male mice.

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