The Sertoli cell marker FOXD1 regulates testis development and function in the chicken

2019 ◽  
Vol 31 (5) ◽  
pp. 867 ◽  
Author(s):  
Xiaofan Yu ◽  
Yangyang Yuan ◽  
Lingyun Qiao ◽  
Yanzhang Gong ◽  
Yanping Feng
Keyword(s):  
Sertoli Cell ◽  
Sertoli Cells ◽  
Quantitative Polymerase Chain Reaction ◽  
Type I ◽  
Regulatory Relationship ◽  
Regulatory Subunits ◽  
Testis Development ◽  
Related Transcription Factor ◽  
And Function ◽  
Relationship Of

FOXD1, one of the transcription factors of the FOX family, has been shown to be important for mammalian reproduction but little is known about its function in avian species. In the present study, we identified the expression pattern and location of FOXD1 in chicken tissues and testis by performing quantitative polymerase chain reaction, immunohistochemistry and immunofluorescence, and further investigated the regulatory relationship of FOXD1 with genes involved in testis development by RNA interference. Our results showed that FOXD1 is confirmed to be significantly male-biased expressed in the brain, kidney and testis of adults as well as in embryonic gonads, and it is localised in the testicular Sertoli cell in chicken, consistent with its localisation in mammals. After knock-down of FOXD1 in chicken Sertoli cells, the expression of anti-Müllerian hormone (AMH), sex-determining region Y-box 9 (SOX9) and PKA regulatory subunits type I α (RIα) was significantly downregulated, expression of androgen receptor (AR) was notably increased whereas double-sex and MAB-3-related transcription factor 1 (DMRT1) showed no obvious change in expression. These results suggest that FOXD1 is an essential marker for Sertoli cells upstream of SOX9 expression and a potential regulator of embryonic testis differentiation and development and of normal testis function in the chicken.

scholarly journals Exogenous Gonadotrophin Stimulation Induces Partial Maturation of Human Sertoli Cells in a Testicular Xenotransplantation Model for Fertility Preservation

2020 ◽  
Vol 9 (1) ◽  
pp. 266 ◽  
Author(s):  
Marsida Hutka ◽  
Lee B. Smith ◽  
Ellen Goossens ◽  
W. Hamish B. Wallace ◽  
Jan-Bernd Stukenborg ◽  
...  
Keyword(s):  
Sertoli Cell ◽  
Sertoli Cells ◽  
Connexin 43 ◽  
Xenograft Model ◽  
Cell Maturation ◽  
Human Testis ◽  
Testicular Development ◽  
Future Fertility ◽  
And Function ◽  
Testis Tissue

The future fertility of prepubertal boys with cancer may be irreversibly compromised by chemotherapy and/or radiotherapy. Successful spermatogenesis has not been achieved following the xenotransplantation of prepubertal human testis tissue, which is likely due to the failure of somatic cell maturation and function. We used a validated xenograft model to identify the factors required for Leydig and Sertoli cell development and function in immature human testis. Importantly, we compared the maturation status of Sertoli cells in xenografts with that of human testis tissues (n = 9, 1 year-adult). Human fetal testis (n = 6; 14–21 gestational weeks) tissue, which models many aspects of prepubertal testicular development, was transplanted subcutaneously into castrated immunocompromised mice for ~12 months. The mice received exogenous human chorionic gonadotropin (hCG; 20IU, 3×/week). In xenografts exposed continuously to hCG, we demonstrate the maintenance of Leydig cell steroidogenesis, the acquisition of features of Sertoli cell maturation (androgen receptor, lumen development), and the formation of the blood–testis barrier (connexin 43), none of which were present prior to the transplantation or in xenografts in which hCG was withdrawn after 7 months. These studies provide evidence that hCG plays a role in Sertoli cell maturation, which is relevant for future investigations, helping them generate functional gametes from immature testis tissue for clinical application.

scholarly journals Extracellular matrix regulates Sertoli cell differentiation, testicular cord formation, and germ cell development in vitro.

1985 ◽  
Vol 101 (4) ◽  
pp. 1511-1522 ◽  
Author(s):  
M A Hadley ◽  
S W Byers ◽  
C A Suárez-Quian ◽  
H K Kleinman ◽  
M Dym
Keyword(s):  
Extracellular Matrix ◽  
Cell Differentiation ◽  
Basement Membrane ◽  
Germ Cell ◽  
Sertoli Cell ◽  
Germ Cells ◽  
Sertoli Cells ◽  
Type I ◽  
Extracellular Matrix Components

Sertoli cell preparations isolated from 10-day-old rats were cultured on three different substrates: plastic, a matrix deposited by co-culture of Sertoli and peritubular myoid cells, and a reconstituted basement membrane gel from the EHS tumor. When grown on plastic, Sertoli cells formed a squamous monolayer that did not retain contaminating germ cells. Grown on the matrix deposited by Sertoli-myoid cell co-cultures, Sertoli cells were more cuboidal and supported some germ cells but did not allow them to differentiate. After 3 wk however, the Sertoli cells flattened to resemble those grown on plastic. In contrast, the Sertoli cells grown on top of the reconstituted basement membrane formed polarized monolayers virtually identical to Sertoli cells in vivo. They were columnar with an elaborate cytoskeleton. In addition, they had characteristic basally located tight junctions and maintained germ cells for at least 5 wk in the basal aspect of the monolayer. However, germ cells did not differentiate. Total protein, androgen binding protein, transferrin, and type I collagen secretion were markedly greater when Sertoli cells were grown on the extracellular matrices than when they were grown on plastic. When Sertoli cells were cultured within rather than on top of reconstituted basement membrane gels they reorganized into cords. After one week, tight junctional complexes formed between adjacent Sertoli cells, functionally compartmentalizing the cords into central (adluminal) and peripheral (basal) compartments. Germ cells within the cords continued to differentiate. Thus, Sertoli cells cultured on top of extracellular matrix components assume a phenotype and morphology more characteristic of the in vivo, differentiated cells. Growing Sertoli cells within reconstituted basement membrane gels induces a morphogenesis of the cells into cords, which closely resemble the organ from which the cells were dissociated and which provide an environment permissive for germ cell differentiation.

232. Developmentally regulated activin A signal transduction by Sertoli cells is required for normal mouse testis development

2008 ◽  
Vol 20 (9) ◽  
pp. 32
Author(s):  
C. M. Itman ◽  
C. Small ◽  
M. Griswold ◽  
A. K. Nagaraja ◽  
M. M. Matzuk ◽  
...  
Keyword(s):  
Signal Transduction ◽  
Sertoli Cell ◽  
Sertoli Cells ◽  
Normal Mouse ◽  
Mouse Testis ◽  
Nuclear Accumulation ◽  
Developmentally Regulated ◽  
Testis Development ◽  
Differentiated Cells ◽  
Immature Cells

Activin A, a TGF-β superfamily ligand, is critical for normal mouse testis development and quantitatively normal sperm production. Testicular activin production changes during development, being substantially higher in the immature testis relative to the adult [1, 2]. Activin influences the Sertoli cell, the nurse cell to developing sperm, enhancing proliferation during its immature phase, but not following terminal differentiation [3]. In the Inha−/− mouse, chronic excessive activin production results in Sertoli cell-derived tumours [4] whereas reduced activin bioactivity, in the InhbaBK/BK mouse, delays fertility [5]. Activin signals are transduced by the phosphorylation and nuclear accumulation of the transcription factors SMAD2 and SMAD3. By comparing activin signal transduction in immature v. terminally differentiated Sertoli cells, using quantitative confocal microscopy and western blot analysis of total and phosphorylated SMAD2 and SMAD3, we discovered that mouse Sertoli cells exhibit developmentally regulated activin responses. Activin induces nuclear accumulation of SMAD3, but not SMAD2, in immature cells, although both proteins are phosphorylated. In contrast, terminally differentiated cells exhibit nuclear accumulation of both SMAD2 and SMAD3. We observed that this shift coincides with decreased SMAD3 production at puberty and changes in FSH-induced Smad transcription, which favours Smad3 in immature cells but promotes Smad2 synthesis in terminally differentiated cells. Furthermore, whereas removal of SMAD3 from the Inha−/− mouse rescues the tumour phenotype [6], we demonstrated that insufficient SMAD3 production impairs testis growth. We hypothesised that this developmentally regulated SMAD utilisation drives specific transcriptional outcomes. Using microarray and quantitative PCR, we identified novel activin target genes displaying developmental stage-specific expression patterns coinciding with differential SMAD usage, including Gja1 and Serpina5 which are required for male fertility. These mRNAs are also modulated in vivo, increased 1.5–2 fold in Inha−/− testes and decreased by half in InhbaBK/BK testes, confirming that normal testis development requires carefully regulated activin production and responsiveness. (1) Buzzard J et al. 2004. Endocrinology 145(7): 3532–3541 (2) Barakat et al. 2008. Reproduction 2008 Epub ahead of print (3) Boitani C et al. 1995. Endocrinology 136(12): 4538–4544 (4) Matzuk M et al. 1992. Nature 360: 313–319 (5) Brown C et al. 2000. Nature Genetics 25(4): 453–457 (6) Li Q et al. 2007. Molecular Endocrinology 21(10: 2472–2486

149. Smad3 DOSAGE INFLUENCES TESTICULAR MATURATION

2009 ◽  
Vol 21 (9) ◽  
pp. 67
Author(s):  
C. Itman ◽  
C. Wong ◽  
D. A. Jans ◽  
M. Ernst ◽  
K. L. Loveland
Keyword(s):  
Cell Proliferation ◽  
Sertoli Cell ◽  
Sertoli Cells ◽  
Post Partum ◽  
Cell Maturation ◽  
Physiological Status ◽  
Testis Weight ◽  
Testis Development ◽  
Smad3 Expression ◽  
Cell Mitogen

Activin A, a TGF-beta superfamily ligand which signals via Smad2 and Smad3, is critical for normal mouse testis development and quantitatively normal sperm production. Whereas activin enhances immature Sertoli cell proliferation (1), excessive activin production causes Sertoli cell tumours (2); this is alleviated when mice lack Smad3 (3). Sertoli cells exhibit developmentally regulated Smad utilization in activin signalling. Immature Sertoli cells signal via Smad3 while the onset of Smad2-mediated signal transduction correlates with Sertoli cell maturation (4). This change coincides with decreased testicular Smad3 production at puberty and a shift in follicle stimulating hormone (FSH)-induced Smad transcription, from Smad3 in 6 dpp (days post partum) Sertoli cells to Smad2 in 15 dpp cells. These findings suggest that Smad3 is more important for testis development than adult spermatogenesis. To test this hypothesis, we examined testis development in Smad3+/– and Smad3–/– mice. At 7 dpp, testis weight and cord diameter were reduced in Smad3–/–mice, indicating impaired Sertoli cell proliferation. Levels of FSH, a potent Sertoli cell mitogen, were unaltered. Histological analysis revealed advanced spermatogenesis in heterozygous mice, with round spermatids already present at 16 dpp. Quantitative PCR also identified advanced Sertoli and germ cell maturation in Smad3+/– mice, while Leydig cell maturation appeared unaltered. Adult Smad3+/– and Smad3–/– mice were fertile, but had smaller testes. This is the first study relating Smad3 levels to puberty onset and identifies the Smad3+/– mouse as a model of peripheral precocious puberty with otherwise normal physiological status, i.e. no gonadal tumours and normal FSH levels. These results demonstrate that FSH influences testis growth and maturation by regulating Smad3 expression and highlights the importance of testing whether environmental factors, toxicants and endocrine disruptors affect Smad3 expression, thereby leading to altered testis development.

The Testicular-Derived Sertoli Cell: Cellular Immunoscience to Enable Transplantation

2003 ◽  
Vol 12 (4) ◽  
pp. 335-349 ◽  
Author(s):  
Dwaine F. Emerich ◽  
Richelle Hemendinger ◽  
Craig R. Halberstadt
Keyword(s):  
Sertoli Cells ◽  
Dopaminergic Neurons ◽  
Type I ◽  
Cure Rate ◽  
Cellular Transplantation ◽  
Islet Allografts ◽  
Edmonton Protocol ◽  
Clinical Disorders ◽  
And Function ◽  
Viable Treatment

There is a renewed enthusiasm for the potential of cellular transplantation as a therapy for numerous clinical disorders. The revived interest is largely due to the unprecedented success of the “Edmonton protocol,” which produced a 100% cure rate for type I diabetics following the transplantation of human islet allografts together with a modified immunosuppressive regimen. While these data provide a clear and unequivocal demonstration that transplantation is a viable treatment strategy, the shortage of suitable donor tissue together with the debilitating consequences of lifelong immunosuppression necessitate a concerted effort to develop novel means to enable transplantation on a widespread basis. This review outlines the use of Sertoli cells to provide local immunoprotection to cografted discordant cells, including those from xenogeneic sources. Sertoli cells are normally found in the testes where one of their functions is to provide local immunologic protection to developing germ cells. Isolated Sertoli cells 1) engraft and self-protect when transplanted into allogeneic and xenogeneic environments, 2) protect cografted allogeneic and xenogeneic cells from immune destruction, 3) protect islet grafts to reverse diabetes in animal models, 4) enable survival and function of cografted foreign dopaminergic neurons in rodent models of Parkinson's disease (PD), and 5) promote regeneration of damaged striatal dopaminergic circuitry in those same PD models. These benefits are discussed in the context of several potential underlying biological mechanisms. While the majority of work to date has focused on Sertoli cells to facilitate transplantation for diabetes and PD, the generalized ability of these unique cells to potently suppress the local immune environment opens additional clinical possibilities.

Adipocytokines may delay pubertal maturation of human Sertoli cells

2019 ◽  
Vol 31 (8) ◽  
pp. 1395 ◽  
Author(s):  
I. V. Wagner ◽  
P. Yango ◽  
K. Svechnikov ◽  
N. D. Tran ◽  
O. Söder
Keyword(s):  
Sertoli Cell ◽  
Sertoli Cells ◽  
Cell Function ◽  
Quantitative Polymerase Chain Reaction ◽  
Term Treatment ◽  
Receptor Expression ◽  
Leukaemia Inhibitory Factor ◽  
Nicotinamide Phosphoribosyltransferase ◽  
Long Term Treatment ◽  
Cytochrome P450 Family

Reproduction is an important target of obesity complications, including adverse effects on spermatogenesis and steroidogenesis. Adipocytokines are key mediators in various complications of obesity. Our aim was to study the potential of adipocytokines to affect Sertoli cell function, which is crucial for spermatogenesis, and possibly link these findings to the observed attenuation of spermatogenesis in obese males. Testicular biopsies were obtained from healthy donors. Highly purified adult human Sertoli cells (HSCs) were isolated by fluorescence-activated cell sorting. Cells were cultured and exposed to different concentrations of adipocytokines (10–1000ngmL−1) for 2–7 days. Expression of selected Sertoli cell genes was quantified by quantitative polymerase chain reaction. Long-term treatment (7 days) of HSCs with higher concentrations of chemerin, irisin, nicotinamide phosphoribosyltransferase (Nampt), resistin and progranulin significantly suppressed FSH receptor expression (by 79%, 83%, 64%, 71% and 26% respectively; P<0.005 for all) and significantly upregulated cytochrome P450 family 26 subfamily A member 1 (CYP26A1) expression (by 48%, 90%, 126%, 126% and 153% respectively P<0.005 for all), comparable to what is found in the prepubertal state. Further, these adipocytokines significantly attenuated the expression of bone morphogenetic protein-4, glial cell line-derived neurotrophic factor, leukaemia inhibitory factor and fibroblast growth factor-2 by HSCs. We propose that adipocytokines, at high concentrations, which are often observed in obese males when tested invitro, may negatively affect Sertoli cell maturation and retain these cells in a more prepubertal stage. This could negatively affect testis function and add to fertility problems in obese adults.

Activin A Determines Steroid Levels and Composition in the Fetal Testis

Endocrinology ◽  
2020 ◽  
Vol 161 (7) ◽  
Author(s):  
Penny A F Whiley ◽  
Liza O’Donnell ◽  
Sarah C Moody ◽  
David J Handelsman ◽  
Julia C Young ◽  
...  
Keyword(s):  
Sertoli Cell ◽  
Sertoli Cells ◽  
Activin A ◽  
Rna Seq ◽  
Testis Development ◽  
Fetal Testis ◽  
Cell Transcriptome ◽  
First Time ◽  
Dose Dependent ◽  
Deficient Mice

Abstract Activin A promotes fetal mouse testis development, including driving Sertoli cell proliferation and cord morphogenesis, but its mechanisms of action are undefined. We performed ribonucleic acid sequencing (RNA-seq) on testicular somatic cells from fetal activin A-deficient mice (Inhba KO) and wildtype littermates at embryonic day (E) E13.5 and E15.5. Analysis of whole gonads provided validation, and cultures with a pathway inhibitor discerned acute from chronic effects of altered activin A bioactivity. Activin A deficiency predominantly affects the Sertoli cell transcriptome. New candidate targets include Minar1, Sel1l3, Vnn1, Sfrp4, Masp1, Nell1, Tthy1 and Prss12. Importantly, the testosterone (T) biosynthetic enzymes present in fetal Sertoli cells, Hsd17b1 and Hsd17b3, were identified as activin-responsive. Activin-deficient testes contained elevated androstenedione (A4), displayed an Inhba gene dose-dependent A4/T ratio, and contained 11-keto androgens. The remarkable accumulation of lipid droplets in both Sertoli and germ cells at E15.5 indicated impaired lipid metabolism in the absence of activin A. This demonstrated for the first time that activin A acts on Sertoli cells to determine local steroid production during fetal testis development. These outcomes reveal how compounds that perturb fetal steroidogenesis can function through cell-specific mechanisms and can indicate how altered activin levels in utero may impact testis development.

Sertoli Cell-Induced Effects on Functional and Structural Characteristics of Isolated Neonatal Porcine Islets

1996 ◽  
Vol 5 (5) ◽  
pp. 517-524 ◽  
Author(s):  
H.P. Selawry ◽  
X. Wang ◽  
L. Alloush
Keyword(s):  
Sertoli Cell ◽  
Sertoli Cells ◽  
Structural Characteristics ◽  
Porcine Pancreas ◽  
Human Donor ◽  
Porcine Islets ◽  
Short Period ◽  
Cryopreservation Techniques ◽  
Neonatal Porcine Islets ◽  
And Function

A lack of a sufficient number of human donor pancreases has stimulated interest in isolation and cryopreservation techniques for islets from the porcine pancreas. But because of a poorly developed outer membrane porcine islets are particularly susceptible to damage during cryopreservation. The aims of this study were twofold: 1) to develop a method for isolation and storage of islets from neonatal porcine pancreas and, 2) to examine effects of Sertoli cells on islet yield and function in Sertoli cell-islet cell cocultures. A total of 170 neonatal porcine pancreases were processed by means of a short period of digestion with collagenase and culture of the tissues at 32°C for periods up to 7 days following isolation. Results were: The mean ±SEM, number of viable islets, and percentage loss of cells following 7 days of culture were 29,442 ± 1,119 and 22.2 ± 1.2, respectively. Cryopreservation had a marked impact on recovery of viable islets: In absence of Sertoli cells an average of only 64% of islets remained viable; by contrast, when cryopreserved islets were cocultured with Sertoli cells, a mean of 82% was recovered. Glucose at 16.7 mmol/L had the capacity to elicit insulin release from 3-day-old cultured islets. The concentration in absence of Sertoli cells was 57.3 ± 3.8, uU/mL/10 islets; in the presence of Sertoli cells the level increased to a mean ± SEM of 112.8 ± 17.7, uU/mL/10 islets. Similar results were obtained following cryopreservation: glucose at 16.7 mmol/L stimulated a mean ± SEM of 27.9 ± 6.6, uU/mL/10 islets, of insulin in absence of, and 44.9 ± 9.9, uU/mL/10 islets, in presence of, Sertoli cells. Our results show that isolation and cryopreservation of neonatal porcine islets can be successfully accomplished. In addition, coculture with Sertoli cells significantly improves both the yield and functional capacity of islets following cryopreservation.

The use of Y-chromosome-specific repeated DNA sequences in the analysis of testis development in an XX/XY mouse

Development ◽  
1987 ◽  
Vol 101 (Supplement) ◽  
pp. 143-149
Author(s):  
Lalji Singh ◽  
Shoichi Matsukuma ◽  
K. W. Jones
Keyword(s):  
Y Chromosome ◽  
Sertoli Cell ◽  
Dna Sequences ◽  
Sertoli Cells ◽  
Dna Probes ◽  
Cellular Composition ◽  
Repeated Dna ◽  
Repeated Dna Sequences ◽  
Testis Development

A study, by means of Y-chromosome-specific repeated DNA probes, of mouse (ST) with small testes is reviewed. Mouse ST was shown to be a somatic mosaic of 10 % XY and 90 % XX cells. The cellular composition of the azoospermic testis reflected the overall proportions of XX and XY cells but it was found that XY cells predominated in the Sertoli cells of the testis tubules. These findings have been interpreted to indicate a fundamental role for the Sertoli cell in inducing testis organization in the indifferent gonadal rudiment, involving the expression of the Y chromosome.

Nuclear export factor 3 is involved in regulating the expression of TGF-β3 in an mRNA export activity-independent manner in mouse Sertoli cells

2013 ◽  
Vol 452 (1) ◽  
pp. 67-78 ◽  
Author(s):  
Yimeng Yin ◽  
Guishuan Wang ◽  
Ning Liang ◽  
Huijuan Zhang ◽  
Zhimin Liu ◽  
...  
Keyword(s):  
Transcriptional Regulation ◽  
Sertoli Cell ◽  
Sertoli Cells ◽  
Translational Control ◽  
Nuclear Export ◽  
Transforming Growth Factor ◽  
Kinase Inhibitor ◽  
Cell Maturation ◽  
Physical Interaction ◽  
Type I

The NXF (nuclear export factor) family members are implicated in the transport of mRNA from the nucleus to the cytoplasm. Recently, some members of the NXF family have been reported to play divergent functional roles, such as post-transcriptional regulation, translational control, regulation of mRNA stability and trafficking. However, little is known about the roles of NXF3 in spermatogenesis. In the present study, we found that mouse NXF3, specifically expressed in principal cells in segment II of the caput epididymis, as well as Sertoli cells in the mouse testis, was required to mediate TGF-β (transforming growth factor β)-induced down-regulation of Tgfb3/TGF-β3 mRNA expression and protein secretion in Sertoli cells. In addition, NXF3 was also involved in TGF-β-induced transcriptional regulation of other genes associated with Sertoli cell maturation and the restructuring of the Sertoli cell BTB (blood–testis barrier), such as Gata1 (GATA-binding protein 1), Wt1 (Wilms's tumour homologue 1), Cldn11 (claudin11) and Cdkn1a (cyclin-dependent kinase inhibitor 1A or p21Cip1). The transcriptional regulation of NXF3 was mediated through physical interaction with STRAP (serine/threonine kinase receptor-associated protein), where NXF3 inhibited the complex formation among Smad7, STRAP and activated type I TGF-β receptor. Taken together, our data provide mechanistic insights into the roles of NXF3 in TGF-β-mediated expression of Tgfb3 and other genes. NXF3 may be implicated in Sertoli cell maturation and the extensive restructuring of the Sertoli cell BTB.

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