Origin and function of embryonic Sertoli cells

2011 ◽  
Vol 2 (6) ◽  
pp. 537-547 ◽  
Author(s):  
Francisco Barrionuevo ◽  
Miguel Burgos ◽  
Rafael Jiménez
Keyword(s):  
Sertoli Cells ◽  
Molecular Mechanisms ◽  
Cell Lineage ◽  
Supporting Cell ◽  
Seminiferous Tubules ◽  
Adult Testis ◽  
Myoid Cell ◽  
Testis Development ◽  
Regulatory Processes ◽  
Testis Differentiation

AbstractIn the adult testis, Sertoli cells (SCs) are the epithelial supporting cells of the seminiferous tubules that provide germ cells (GCs) with the required nutrients and structural and regulatory support to complete spermatogenesis. SCs also form the blood-testis barrier, phagocytose apoptotic spermatocytes and cell debris derived from spermiogenesis, and produce and secrete numerous paracrine and endocrine signals involved in different regulatory processes. In addition to their essential functions in the adult testis, SCs play a pivotal role during testis development. They are the first cells to differentiate in the embryonic XY gonadal primordium and are involved in the regulation of testis-specific differentiation processes, such as prevention of GC entry into meiosis, Leydig and peritubular myoid cell differentiation, and regression of the Müllerian duct, the anlagen of the uterus, oviducts, and the upper part of the vagina. Expression of the Y-linked gene SRY in pre-SCs initiates a genetic cascade that leads to SC differentiation and subsequently to testis development. Since the identification of the SRY gene, many Sertoli-specific transcription factors and signals underlying the molecular mechanisms of early testis differentiation have been identified. Here, we review the state of the art of the molecular interactions that commit the supporting cell lineage of the gonadal primordium to differentiate as SCs and the subsequent Sertoli-specific signaling pathways involved in early testis differentiation.

scholarly journals RUNX1 maintains the identity of the fetal ovary through an interplay with FOXL2

2019 ◽  
Vol 10 (1) ◽  
Author(s):  
Barbara Nicol ◽  
Sara A. Grimm ◽  
Frédéric Chalmel ◽  
Estelle Lecluze ◽  
Maëlle Pannetier ◽  
...  
Keyword(s):  
Transcription Factor ◽  
Granulosa Cell ◽  
Sertoli Cells ◽  
Transcriptional Control ◽  
Cell Lineage ◽  
Supporting Cell ◽  
Supporting Cells ◽  
Fate Specification ◽  
Fetal Ovary

Abstract Sex determination of the gonads begins with fate specification of gonadal supporting cells into either ovarian pre-granulosa cells or testicular Sertoli cells. This fate specification hinges on a balance of transcriptional control. Here we report that expression of the transcription factor RUNX1 is enriched in the fetal ovary in rainbow trout, turtle, mouse, goat, and human. In the mouse, RUNX1 marks the supporting cell lineage and becomes pre-granulosa cell-specific as the gonads differentiate. RUNX1 plays complementary/redundant roles with FOXL2 to maintain fetal granulosa cell identity and combined loss of RUNX1 and FOXL2 results in masculinization of fetal ovaries. At the chromatin level, RUNX1 occupancy overlaps partially with FOXL2 occupancy in the fetal ovary, suggesting that RUNX1 and FOXL2 target common sets of genes. These findings identify RUNX1, with an ovary-biased expression pattern conserved across species, as a regulator in securing the identity of ovarian-supporting cells and the ovary.

scholarly journals Establishment and applications of male germ cell and Sertoli cell lines

Reproduction ◽  
2016 ◽  
Vol 152 (2) ◽  
pp. R31-R40 ◽  
Author(s):  
Hong Wang ◽  
Liping Wen ◽  
Qingqing Yuan ◽  
Min Sun ◽  
Minghui Niu ◽  
...  
Keyword(s):  
Cell Line ◽  
Sertoli Cell ◽  
Cell Lines ◽  
Germ Cells ◽  
Sertoli Cells ◽  
Molecular Mechanisms ◽  
Simian Virus 40 ◽  
T Antigen ◽  
Seminiferous Tubules ◽  
Male Germ Cells

Within the seminiferous tubules there are two major cell types, namely male germ cells and Sertoli cells. Recent studies have demonstrated that male germ cells and Sertoli cells can have significant applications in treating male infertility and other diseases. However, primary male germ cells are hard to proliferatein vitroand the number of spermatogonial stem cells is scarce. Therefore, methods that promote the expansion of these cell populations are essential for their use from the bench to the bed side. Notably, a number of cell lines for rodent spermatogonia, spermatocytes and Sertoli cells have been developed, and significantly we have successfully established a human spermatogonial stem cell line with an unlimited proliferation potential and no tumor formation. This newly developed cell line could provide an abundant source of cells for uncovering molecular mechanisms underlying human spermatogenesis and for their utilization in the field of reproductive and regenerative medicine. In this review, we discuss the methods for establishing spermatogonial, spermatocyte and Sertoli cell lines using various kinds of approaches, including spontaneity, transgenic animals with oncogenes, simian virus 40 (SV40) large T antigen, the gene coding for a temperature-sensitive mutant ofp53, telomerase reverse gene (Tert), and the specific promoter-based selection strategy. We further highlight the essential applications of these cell lines in basic research and translation medicine.

scholarly journals Benzo(a)pyrene (B[a]P) and its adverse effects on male testis

2018 ◽  
Author(s):  
Wei Liu ◽  
Aihua Gu
Keyword(s):  
Body Weight ◽  
Sertoli Cells ◽  
Molecular Mechanisms ◽  
Treated Group ◽  
Male Reproduction ◽  
Adverse Impact ◽  
Phase Cell ◽  
Seminiferous Tubules ◽  
Blood Testis Barrier

ABSTRACTIt has been proved that Benzo(a)pyrene (B[a]P) is mutagenic in somatic cells, whereas the adverse effect of BaP on male reproduction remains unclear. To investigate whether it can pass through the blood-testis barrier (BTB) and its potential reproductive toxicology and molecular mechanisms, mice were exposed to B[a]P (there are two doses, that is 13mg/kg body weight and 26 mg/kg body weight; three times per week) during 6 weeks and sacrificed 6 weeks after the final exposure to obtain B[a]P-exposed testis, blood and others. Electron microscopy analysis was performed to confirm whether the integrity of BTB and the ultra-structure changes in testes of B[a]P treated mice, which showed that the integrity of the BTB was disrupted, accompanied with the structure of sertoli cells seriously damaged, including the integrity of the nuclear membrane of the sertoli cells impaired and the basement membrane of the seminiferous tubules disrupted. X-ray imaging in vitro told us that BaP can overgo the BTB and gathered in the testis of mice. We found the significantly decreased expression of ZO-1, occludin, N-cadherin, vimentin and claudin-1 in the testes of B[a]P treated group by immunofluorescence detection. B[a]P induced BTB component protein decreased were also found in TM4 cells exposed to 5μmol/L B[a]P for 24h. We found a significantly decrease of testosterone level and a significantly increase of estrogen level in the serum of treated groups comparing with the control one by radioimmunoassay. TM4 cells, MLTC-1 cells and GC-2 cells was cultured with medium contains B[a]P. MTT Cell Proliferation and Cytotoxicity Assay, cell apoptosis analysis, FACScan analyzer, We observed apparent increase of TM4 and GC-2 cells apoptosis after expose to B[a]P for 24h. B[a]P induced TM4 cell, GC-2 cell and MLTC-1 cell G2/M phase cell arrest. In conclusion, these results suggested that BaP has an adverse impact on male reproduction, it can cross the blood-testis barrier and damage it, the component proteins of the BTB significantly decreased, it can also produce adverse impact on male germ cells.

scholarly journals XY follicle cells in the ovaries of XO/XY and XO/XY/XYY mosaic mice

Development ◽  
1991 ◽  
Vol 111 (4) ◽  
pp. 1017-1019 ◽  
Author(s):  
S.J. Palmer ◽  
P.S. Burgoyne
Keyword(s):  
Sertoli Cells ◽  
Ovarian Development ◽  
In Situ Hybridisation ◽  
Cell Lineage ◽  
Supporting Cell ◽  
Follicle Cells ◽  
Cell Lineages ◽  
Determination Process ◽  
Testis Determination

XO/XY and XO/XY/XYY mosaic hermaphrodites were generated from crosses involving BALB/cWt males. The distribution of Y-bearing cells in the gonads of these mice was studied by in situ hybridisation using the Y-specific probe pY353B. XY cells were found to contribute to all cell lineages of the ovary including follicle cells. The proportion of XY follicle cells was not significantly different from the XY contribution to other gonadal or non-gonadal cell lineages. However, this proportion was consistently low, all the hermaphrodites having a low XY contribution to the animal as a whole. Because the XO- and Y-bearing cell lineages are developmentally balanced, the XY follicle cells cannot have formed as a result of a ‘mismatch’ in which the Y-directed testis determination process is pre-empted by an early acting programme of ovarian development. These results are discussed with respect to the hypothesis that Tdy acts in the supporting cell lineage, the lineage from which Sertoli cells and follicle cells are believed to be derived.

Differentiation of Fetal Sertoli Cells in the Adult Testis

Reproduction ◽  
2021 ◽  
Author(s):  
Tetsuhiro Yokonishi ◽  
Blanche Capel
Keyword(s):  
Sertoli Cell ◽  
Sertoli Cells ◽  
Developmental Process ◽  
Ips Cells ◽  
Cell Maturation ◽  
Seminiferous Tubules ◽  
Fetal Life ◽  
Adult Testis ◽  
Testicular Cells

Sertoli cells proliferate and construct seminiferous tubules during fetal life, then undergo differentiation and maturation in the prepubertal testes. In the adult testes, mature Sertoli cells maintain spermatogonia and support spermatogenesis during the entire lifetime. Although Sertoli-like cells have been derived from iPS cells, they tend to remain immature. To investigate whether Sertoli cells can spontaneously acquire the ability to support spermatogenesis when transferred into the adult testis, we transplanted mouse fetal testicular cells into a Sertoli-depleted adult testis. We found that donor E12.5, E14.5 and E16.5 Sertoli cells colonized adult seminiferous tubules and supported host spermatogenesis two months after transplantation, demonstrating that immature fetal Sertoli cells can undergo sufficient maturation in the adult testis to become functional. This technique will be useful to analyze the developmental process of Sertoli cell maturation, and to investigate the potential of iPS-derived Sertoli cells to colonize, undergo maturation, and support spermatogenesis within the testis environment.

scholarly journals Effect of Cryptorchidism on the Histomorphometry, Proliferation, Apoptosis, and Autophagy in Boar Testes

Animals ◽  
2021 ◽  
Vol 11 (5) ◽  
pp. 1379
Author(s):  
Xiaorui Fan ◽  
Yihui Liu ◽  
Meishan Yue ◽  
Weidong Yue ◽  
Gaoya Ren ◽  
...  
Keyword(s):  
Germ Cells ◽  
Sertoli Cells ◽  
Proliferating Cell Nuclear Antigen ◽  
Molecular Mechanisms ◽  
Inguinal Canal ◽  
The Body ◽  
Nuclear Antigen ◽  
Seminiferous Tubules ◽  
Mrna Levels ◽  
Proliferating Cell

Spontaneous unilateral cryptorchid boars have one testis in the abdomen or inguinal canal, causing its temperature to be at or near the body temperature, which impairs spermatogenesis, although the histomorphometry and molecular mechanisms underlying this process remain unclear. The aim of the present study was to determine the histomorphometry, proliferation, apoptosis, and autophagy alterations in spermatogonia and Sertoli cells in unilateral cryptorchid, scrotal (contrascrotal), and preweaning piglet (preweaning) testes. Histomorphometrical analysis of cryptorchid testes showed that the seminiferous tubules contained only Sertoli cells and a few spermatogonia, but did not contain post-meiotic germ cells. The number of spermatogonia markedly decreased, and the number of Sertoli cells did not change remarkably in cryptorchid testes. TUNEL assay results showed that apoptosis signals were predominantly observed in spermatogonia. In cryptorchid and contrascrotal testes, proliferating cell nuclear antigen (PCNA) and LC3 were located in spermatogonia. The number of PCNA-positive, TUNEL-positive, and LC3-positive germ cells was low, and the protein and mRNA levels of PCNA and LC3 were significantly decreased in cryptorchid testes. Taken together, the number of Sertoli cells did not change remarkably, whereas the number of germ cells decreased in the cryptorchid testes, compared with that in the contrascrotal testes. Insufficient proliferation, excessive apoptosis, and autophagy were involved in the regulation of the decrease in spermatogonia in cryptorchid boar testes.

scholarly journals Regulation of seminiferous tubule-associated stem Leydig cells in adult rat testes

2016 ◽  
Vol 113 (10) ◽  
pp. 2666-2671 ◽  
Author(s):  
Xiaoheng Li ◽  
Zhao Wang ◽  
Zhenming Jiang ◽  
Jingjing Guo ◽  
Yuxi Zhang ◽  
...  
Keyword(s):  
Stem Cells ◽  
Growth Factor ◽  
Leydig Cell ◽  
Leydig Cells ◽  
Cell Lineage ◽  
Seminiferous Tubules ◽  
Paracrine Factors ◽  
Adult Testis ◽  
Adult Leydig Cells ◽  
Neonatal Testis

Testicular Leydig cells are the primary source of testosterone in males. Adult Leydig cells have been shown to arise from stem cells present in the neonatal testis. Once established, adult Leydig cells turn over only slowly during adult life, but when these cells are eliminated experimentally from the adult testis, new Leydig cells rapidly reappear. As in the neonatal testis, stem cells in the adult testis are presumed to be the source of the new Leydig cells. As yet, the mechanisms involved in regulating the proliferation and differentiation of these stem cells remain unknown. We developed a unique in vitro system of cultured seminiferous tubules to assess the ability of factors from the seminiferous tubules to regulate the proliferation of the tubule-associated stem cells, and their subsequent entry into the Leydig cell lineage. The proliferation of the stem Leydig cells was stimulated by paracrine factors including Desert hedgehog (DHH), basic fibroblast growth factor (FGF2), platelet-derived growth factor (PDGF), and activin. Suppression of proliferation occurred with transforming growth factor β (TGF-β). The differentiation of the stem cells was regulated positively by DHH, lithium- induced signaling, and activin, and negatively by TGF-β, PDGFBB, and FGF2. DHH functioned as a commitment factor, inducing the transition of stem cells to the progenitor stage and thus into the Leydig cell lineage. Additionally, CD90 (Thy1) was found to be a unique stem cell surface marker that was used to obtain purified stem cells by flow cytometry.

scholarly journals The Rete Testis: Development and Role in Testis Function

2021 ◽  
Vol 52 (6) ◽  
pp. 370-378
Author(s):  
A. Yu. Kulibin ◽  
E. A. Malolina
Keyword(s):  
Stem Cells ◽  
Sex Determination ◽  
Germ Cells ◽  
Sertoli Cells ◽  
Rete Testis ◽  
The Other ◽  
Seminiferous Tubules ◽  
Testis Development ◽  
Stage Of Development ◽  
Efferent Ducts

Abstract The rete testis connects seminiferous tubules in which germ cells develop to the efferent ducts and the epididymis, where gametes mature and gain mobility. Several recent studies have thoroughly explored the morphogenesis of this structure in mice during embryonic and postnatal periods. A part of the rete testis has been shown to derive from the precursors of gonad somatic cells before sex determination. The other part forms from embryonal Sertoli cells of testis cords adjacent to the mesonephros. The transformation of Sertoli cells into rete testis cells is apparently not limited to the embryonic stage of development and continues during postnatal testis development. Recently, it was found that the rete testis participates in the formation and maintenance of specialized Sertoli cells in terminal segments of seminiferous tubules, transitional zones. Current views suggest that the transitional zones of the seminiferous tubules may represent a niche for spermatogonial stem cells, the site of the prolonged proliferation of Sertoli cells in the pubertal and postpubertal periods of testis development, and also could be a generator of spermatogenic waves. To sum up, the rete testis transports gametes from the testis to the epididymis, maintains pressure within seminiferous tubules, regulates the composition of the testicular fluid, and impacts the spermatogenic process itself.

scholarly journals Sox9 and Sox8 protect the adult testis from male-to-female genetic reprogramming and complete degeneration

eLife ◽  
2016 ◽  
Vol 5 ◽  
Author(s):  
Francisco J Barrionuevo ◽  
Alicia Hurtado ◽  
Gwang-Jin Kim ◽  
Francisca M Real ◽  
Mohammed Bakkali ◽  
...  
Keyword(s):  
Sertoli Cells ◽  
Male Fertility ◽  
Leydig Cells ◽  
Structural Proteins ◽  
Seminiferous Tubules ◽  
Adult Testis ◽  
Key Genes ◽  
Male To Female ◽  
Mutant Cells ◽  
Testis Regression

The new concept of mammalian sex maintenance establishes that particular key genes must remain active in the differentiated gonads to avoid genetic sex reprogramming, as described in adult ovaries after Foxl2 ablation. Dmrt1 plays a similar role in postnatal testes, but the mechanism of adult testis maintenance remains mostly unknown. Sox9 and Sox8 are required for postnatal male fertility, but their role in the adult testis has not been investigated. Here we show that after ablation of Sox9 in Sertoli cells of adult, fertile Sox8-/- mice, testis-to-ovary genetic reprogramming occurs and Sertoli cells transdifferentiate into granulosa-like cells. The process of testis regression culminates in complete degeneration of the seminiferous tubules, which become acellular, empty spaces among the extant Leydig cells. DMRT1 protein only remains in non-mutant cells, showing that SOX9/8 maintain Dmrt1 expression in the adult testis. Also, Sox9/8 warrant testis integrity by controlling the expression of structural proteins and protecting Sertoli cells from early apoptosis. Concluding, this study shows that, in addition to its crucial role in testis development, Sox9, together with Sox8 and coordinately with Dmrt1, also controls adult testis maintenance.

scholarly journals Developmental expression and spermatogenic stage specificity of transcription factors GATA-1 and GATA-4 and their cofactors FOG-1 and FOG-2 in the mouse testis

2002 ◽  
pp. 397-406 ◽  
Author(s):  
I Ketola ◽  
M Anttonen ◽  
T Vaskivuo ◽  
JS Tapanainen ◽  
J Toppari ◽  
...  
Keyword(s):  
Transcription Factors ◽  
Sertoli Cells ◽  
Gonadal Development ◽  
Developmental Expression ◽  
Seminiferous Tubules ◽  
Testicular Development ◽  
Adult Testis ◽  
Stage Specificity ◽  
And Function

OBJECTIVE: The transcription factors GATA-1 and GATA-4 have been implicated in the regulation of testicular development and function. Their cofactors FOG-1 and FOG-2 are expressed in the gonads, but their cell-specific and developmental expression in the testis remains unresolved. Therefore, we analyzed GATA-1, GATA-4, FOG-1 and FOG-2 expression in detail, from undifferentiated male urogenital ridge to adult testis. METHODS: Immunohistochemistry and in situ hybridization were applied on mouse testicular samples. RESULTS: GATA-4 and FOG-2, but not GATA-1 or FOG-1, were expressed as early as in the male urogenital ridge. FOG-2 expression was localized in the Sertoli cells at embryonal day 12.5 (E12.5), but it diminished with advancing fetal testicular development. In E17.5 testis, FOG-2 was present only in the testicular capsule and a subset of fetal Leydig cells. FOG-1 was expressed from E15.5 Sertoli cells onwards, whereas GATA-1 was not detected during the fetal period at all. In the postnatal testis, FOG-2 was abundantly expressed immediately after birth, but in adult testis its expression was predominantly restricted to stage VII-XII seminiferous tubules. Stage specificity was also found for FOG-1, which, similarly to GATA-1, was abundantly expressed in stage VII-XII tubules during adulthood. CONCLUSIONS: Our results indicate that FOG-2, in addition to GATA-4, has a role in early gonadal development and sexual differentiation, and FOG-1 at later fetal stages, while GATA-1 executes its action postnatally. The findings suggest that, in contrast to the hematopoietic system and the heart, GATA-1 and GATA-4 do not use FOG-1 and FOG-2 respectively as their only cofactors during the early stages of testicular development.

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