scholarly journals Regulation of spermatogonial stem cell self-renewal and spermatocyte meiosis by Sertoli cell signaling

Reproduction ◽  
2015 ◽  
Vol 149 (4) ◽  
pp. R159-R167 ◽  
Author(s):  
Su-Ren Chen ◽  
Yi-Xun Liu
Keyword(s):  
Transcription Factors ◽  
Signaling Pathways ◽  
Sertoli Cell ◽  
Sertoli Cells ◽  
Seminiferous Tubules ◽  
Self Renewal ◽  
Cxcr4 Signaling ◽  
Proliferation And Differentiation ◽  
Luminal Side ◽  
Productive Process

Spermatogenesis is a continuous and productive process supported by the self-renewal and differentiation of spermatogonial stem cells (SSCs), which arise from undifferentiated precursors known as gonocytes and are strictly controlled in a special ‘niche’ microenvironment in the seminiferous tubules. Sertoli cells, the only somatic cell type in the tubules, directly interact with SSCs to control their proliferation and differentiation through the secretion of specific factors. Spermatocyte meiosis is another key step of spermatogenesis, which is regulated by Sertoli cells on the luminal side of the blood–testis barrier through paracrine signaling. In this review, we mainly focus on the role of Sertoli cells in the regulation of SSC self-renewal and spermatocyte meiosis, with particular emphasis on paracrine and endocrine-mediated signaling pathways. Sertoli cell growth factors, such as glial cell line-derived neurotrophic factor (GDNF) and fibroblast growth factor 2 (FGF2), as well as Sertoli cell transcription factors, such as ETS variant 5 (ERM; also known as ETV5), nociceptin, neuregulin 1 (NRG1), and androgen receptor (AR), have been identified as the most important upstream factors that regulate SSC self-renewal and spermatocyte meiosis. Other transcription factors and signaling pathways (GDNF–RET–GFRA1 signaling, FGF2–MAP2K1 signaling, CXCL12–CXCR4 signaling, CCL9–CCR1 signaling, FSH–nociceptin/OPRL1, retinoic acid/FSH–NRG/ERBB4, and AR/RB–ARID4A/ARID4B) are also addressed.

scholarly journals Regulation of GDNF expression in Sertoli cells

Reproduction ◽  
2019 ◽  
Author(s):  
Parag Parekh ◽  
Thomas Xavier Garcia ◽  
Marie-claude Hofmann
Keyword(s):  
Germ Cell ◽  
Sertoli Cells ◽  
Seminiferous Tubules ◽  
Receptor Complex ◽  
Myoid Cells ◽  
Self Renewal ◽  
Cell Proliferation And Differentiation ◽  
Proliferation And Differentiation ◽  
Direct Cell ◽  
Ability To Drive

Sertoli cells regulate male germ cell proliferation and differentiation and are a critical component of the spermatogonial stem cell (SSC) niche, where homeostasis is maintained by the interplay of several signaling pathways and growth factors. These factors are secreted by Sertoli cells located within the seminiferous epithelium, and by interstitial cells residing between the seminiferous tubules. Sertoli cells and peritubular myoid cells produce glial cell line-derived neurotrophic factor (GDNF), which binds to the RET/GFRA1 receptor complex at the surface of undifferentiated spermatogonia. GDNF is known for its ability to drive SSC self-renewal and proliferation of their direct cell progeny. Even though the effects of GDNF are well studied, our understanding of the regulation its expression is still limited. The purpose of this review is to discuss how GDNF expression in Sertoli cells is modulated within the niche, and how these mechanisms impact germ cell homeostasis.

Developmental stage- and spermatogenic cycle-specific expression of transcription factor GATA-1 in mouse Sertoli cells

Development ◽  
1994 ◽  
Vol 120 (7) ◽  
pp. 1759-1766 ◽  
Author(s):  
K. Yomogida ◽  
H. Ohtani ◽  
H. Harigae ◽  
E. Ito ◽  
Y. Nishimune ◽  
...  
Keyword(s):  
Transcription Factor ◽  
Developmental Stage ◽  
Sertoli Cell ◽  
Germ Cells ◽  
Sertoli Cells ◽  
Transcriptional Activation ◽  
Germ Line ◽  
Mouse Testis ◽  
Seminiferous Tubules ◽  
Specific Expression

GATA-1 is an essential factor for the transcriptional activation of erythroid-specific genes, and is also abundantly expressed in a discrete subset of cells bordering the seminiferous epithelium in tubules of the murine testis. In examining normal and germ-line defective mutant mice, we show here that GATA-1 is expressed only in the Sertoli cell lineage in mouse testis. GATA-1 expression in Sertoli cells is induced concomitantly with the first wave of spermatogenesis, and GATA-1-positive cells are uniformly distributed among all tubules during prepubertal testis development. However, the number of GATA-1-positive cells declines thereafter and were found only in the peripheral zone of seminiferous tubules in stages VII, VIII and IX of spermatogenesis in the adult mouse testis. In contrast, virtually every Sertoli cell in mutant W/Wv, jsd/jsd or cryptorchid mice (all of which lack significant numbers of germ cells) expresses GATA-1, thus showing that the expression of this transcription factor is negatively controlled by the maturing germ cells. These observations suggest that transcription factor GATA-1 is a developmental stage- and spermatogenic cycle-specific regulator of gene expression in Sertoli cells.

148. HORMONALLY REGULATED miRNAS TARGET THE TUBULOBULBAR COMPLEX IN THE TESTIS

2010 ◽  
Vol 22 (9) ◽  
pp. 66
Author(s):  
P. K. Nicholls ◽  
P. G. Stanton ◽  
K. L. Walton ◽  
R. I. McLachlan ◽  
L. O'Donnell ◽  
...  
Keyword(s):  
Sertoli Cell ◽  
Sertoli Cells ◽  
Hormonal Regulation ◽  
Focal Adhesions ◽  
Intercellular Junctions ◽  
Protein Translation ◽  
Seminiferous Epithelium ◽  
Seminiferous Tubules ◽  
Micro Rnas

Spermatogenesis is absolutely dependent on follicle stimulating hormone (FSH) and androgens; acute suppression of these hormones inhibits germ cell development and thus sperm production. The removal of intercellular junctions and release of spermatids by the Sertoli cell, a process known as spermiation, is particularly sensitive to acute hormone suppression(1). To define the molecular mechanisms that mediate FSH and androgen effects in the testis, we investigated the expression and hormonal regulation of micro-RNAs (miRNA), small non-coding RNAs that regulate protein translation and modify cellular responses. By array analysis, we identified 23 miRNAs that were upregulated >2-fold in stage VIII seminiferous tubules following hormone suppression, and in vitro in primary Sertoli cells. We subsequently validated the expression and hormonal regulation of several miRNAs, including miR-23b, -30d and -690 by quantitative PCR in primary Sertoli cells. Bioinformatic analysis of potential targets of hormonally-suppressed miRNAs identified genes associated with Focal adhesions (54 genes, P = –ln(17.97)) and the Regulation of the actin cytoskeleton (52 genes, P = –ln(10.16)), processes known to be intimately associated with adhesion of spermatids to Sertoli cells(2, 3). Furthermore, this analysis identified numerous components of the testicular tubulobulbar complex (TBC) as being targets of hormonally sensitive miRNAs. The TBC is a podosome-like structure between Sertoli and adjacent spermatids in the testis, which internalises intact inter-cellular junctions by endocytotic mechanisms prior to spermiation(4). We then demonstrate the hormonal regulation of predicted miRNA target proteins, and validate novel inhibitory miRNA interactions with Pten, nWASP, Eps15 and Picalm by luciferase knockdown in vitro. We hypothesise that hormonally suppressed miRNAs inhibit TBC function, and subsequently, endocytosis of intercellular junctions. In conclusion, we have demonstrated that hormonal suppression in the testis stimulates the expression of a subset of Sertoli cell miRNAs that are likely regulators of cell adhesion protein networks involved in spermiation. (1) Saito K, O’Donnell L, McLachlan RI, Robertson DM 2000 Spermiation failure is a major contributor to early spermatogenic suppression caused by hormone withdrawal in adult rats. Endocrinology 141: 2779–2.(2) O’Donnell L, Stanton PG, Bartles JR, Robertson DM 2000 Sertoli cell ectoplasmic specializations in the seminiferous epithelium of the testosterone-suppressed adult rat. Biol Reprod 63: 99–108.(3) Beardsley A, Robertson DM, O’Donnell L 2006 A complex containing alpha6beta1-integrin and phosphorylated focal adhesion kinase between Sertoli cells and elongated spermatids during spermatid release from the seminiferous epithelium. J Endocrinol 190(3): 759–70.(4) Young JS, Guttman JA, Vaid KS, Vogl AW 2009 Tubulobulbar complexes are intercellular podosome-like structures that internalize intact intercellular junctions during epithelial remodeling events in the rat testis. Biol Reprod 80: 162–74.

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.

A combination of insulin-like growth factor I (IGF-I) and FSH promotes proliferation of prepubertal bovine Sertoli cells isolated and cultured in vitro

2017 ◽  
Vol 29 (8) ◽  
pp. 1635 ◽  
Author(s):  
A. Dance ◽  
J. Kastelic ◽  
J. Thundathil
Keyword(s):  
Growth Factor ◽  
Sertoli Cell ◽  
Sertoli Cells ◽  
Seminiferous Tubules ◽  
Insulin Like Growth Factor ◽  
Factor I ◽  
Bull Calves ◽  
Igf I ◽  
Growth Factor I

Beef and dairy bull calves fed a low-nutrition diet during early life had decreased concentrations of circulating insulin-like growth factor I (IGF-I), delayed increases in testosterone, smaller testes and delayed puberty compared with those fed high-nutrition diets. Although IGF-1 has important roles in Sertoli cell function in rats and mice, this has not been well documented in bulls. The objectives of this study were to: (1) isolate Sertoli cells from bull calves at 8 weeks of age, (2) culture them in vitro and (3) determine the effects of IGF-I, FSH and a combination of both hormones on cell proliferation. For Sertoli cell isolation, minced testicular tissues were treated with collagenase followed by trypsin and hyaluronidase to digest seminiferous tubules and release Sertoli cells. In this study, Sertoli cells were successfully isolated from 8-week-old Holstein bull calves (n = 4) and these cells were cultured for up to 8 days. A combination of IGF-I and FSH increased proliferation (~18%) and therefore cell number (1.5-fold) of prepubertal bovine Sertoli cells in culture, providing clear evidence that IGF-I has a similar role in bovine Sertoli cells as reported in rodents.

scholarly journals Cyclic Expression of Endothelin-converting Enzyme-1 Mediates the Functional Regulation of Seminiferous Tubule Contraction

1999 ◽  
Vol 145 (5) ◽  
pp. 1027-1038 ◽  
Author(s):  
Antonella Tripiciano ◽  
Carmelina Peluso ◽  
Anna Rita Morena ◽  
Fioretta Palombi ◽  
Mario Stefanini ◽  
...  
Keyword(s):  
Sertoli Cell ◽  
Sertoli Cells ◽  
Seminiferous Tubule ◽  
Seminiferous Epithelium ◽  
Seminiferous Tubules ◽  
Converting Enzyme ◽  
Myoid Cells ◽  
Endothelin 1 ◽  
Endothelin Converting Enzyme ◽  
Cyclic Expression

The potent smooth muscle agonist endothelin-1 (ET-1) is involved in the local control of seminiferous tubule contractility, which results in the forward propulsion of tubular fluid and spermatozoa, through its action on peritubular myoid cells. ET-1, known to be produced in the seminiferous epithelium by Sertoli cells, is derived from the inactive intermediate big endothelin-1 (big ET-1) through a specific cleavage operated by the endothelin-converting enzyme (ECE), a membrane-bound metalloprotease with ectoenzymatic activity. The data presented suggest that the timing of seminiferous tubule contractility is controlled locally by the cyclic interplay between different cell types. We have studied the expression of ECE by Sertoli cells and used myoid cell cultures and seminiferous tubule explants to monitor the biological activity of the enzymatic reaction product. Northern blot analysis showed that ECE-1 (and not ECE-2) is specifically expressed in Sertoli cells; competitive enzyme immunoassay of ET production showed that Sertoli cell monolayers are capable of cleaving big ET-1, an activity inhibited by the ECE inhibitor phosphoramidon. Microfluorimetric analysis of intracellular calcium mobilization in single cells showed that myoid cells do not respond to big endothelin, nor to Sertoli cell plain medium, but to the medium conditioned by Sertoli cells in the presence of big ET-1, resulting in cell contraction and desensitization to further ET-1 stimulation; in situ hybridization analysis shows regional differences in ECE expression, suggesting that pulsatile production of endothelin by Sertoli cells (at specific “stages” of the seminiferous epithelium) may regulate the cyclicity of tubular contraction; when viewed in a scanning electron microscope, segments of seminiferous tubules containing the specific stages characterized by high expression of ECE were observed to contract in response to big ET-1, whereas stages with low ECE expression remained virtually unaffected. These data indicate that endothelin-mediated spatiotemporal control of rhythmic tubular contractility might be operated by Sertoli cells through the cyclic expression of ECE-1, which is, in turn, dependent upon the timing of spermatogenesis.

scholarly journals E4 Transcription Factor 1 (E4F1) Regulates Sertoli Cell Proliferation and Fertility in Mice

Animals ◽  
2020 ◽  
Vol 10 (9) ◽  
pp. 1691
Author(s):  
Rong-Ge Yan ◽  
Qi-Lin Yang ◽  
Qi-En Yang
Keyword(s):  
Cell Proliferation ◽  
Transcription Factor ◽  
Sertoli Cell ◽  
Sertoli Cells ◽  
Cell Function ◽  
Conditional Knockout ◽  
Seminiferous Tubules ◽  
Quiescent State ◽  
Testis Size ◽  
Cell Fate Decisions

In the mammalian testes, Sertoli cells are the only somatic cells in the seminiferous tubules that provide structural, nutritional and regulatory support for developing spermatogenic cells. Sertoli cells only proliferate during the fetal and neonatal periods and enter a quiescent state after puberty. Functional evidences suggest that the size of Sertoli cell population determines sperm production and fertility. However, factors that direct Sertoli cell proliferation and maturation are not fully understood. Transcription factor E4F1 is a multifunctional protein that serves essential roles in cell fate decisions and because it interacts with pRB, a master regulator of Sertoli cell function, we hypothesized that E4F1 may have a functional role in Sertoli cells. E4f1 mRNA was present in murine testis and immunohistochemical staining confirmed that E4F1 was enriched in mature Sertoli cells. We generated a conditional knockout mouse model using Amh-cre and E4f1flox/flox lines to study E4F1 fucntion in Sertoli cells and the results showed that E4f1 deletion caused a significant reduction in testis size and fertility. Further analyses revealed that meiosis progression and spermiogenesis were normal, however, Sertoli cell proliferation was impaired and germ cell apoptosis was elevated in the testis of E4f1 conditional knockout mice. On the basis of these findings, we concluded that E4F1 was expressed in murine Sertoli cells and served important functions in regulating Sertoli cell proliferation and fertility.

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.

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.

Androgen Insensitivity Syndrome

1999 ◽  
Vol 123 (3) ◽  
pp. 225-234
Author(s):  
Javier Regadera ◽  
Francisco Martínez-García ◽  
Ricardo Paniagua ◽  
Manuel Nistal
Keyword(s):  
Sertoli Cell ◽  
Sertoli Cells ◽  
Smooth Muscle Actin ◽  
Androgen Insensitivity Syndrome ◽  
Collagen Iv ◽  
Adult Patients ◽  
Seminiferous Tubules ◽  
Cell Hyperplasia ◽  
Androgen Insensitivity ◽  
Lesion Pattern

Abstract Objective.—To evaluate the morphometric, immunohistochemical, and ultrastructural lesions of the testes in prepubertal and adult patients with androgen insensitivity syndrome. Methods.—We examined the testicular biopsy using immunohistochemistry for vimentin, smooth muscle actin, and collagen IV antigens. Quantification of seminiferous tubules and testicular interstitium was performed in prepubertal and adult patients with androgen insensitivity syndrome and results were compared with normal testes from both infants and adults. Results.—The adult testes presented nodular and diffuse lesions that consisted of Sertoli-cell-only seminiferous tubules. Two types of Sertoli cells could be distinguished, namely, immature vimentin-positive Sertoli cells and nearly mature Sertoli cells. In the nodules, the lamina propria was thin and contained a scant number of actin-positive peritubular cells. Leydig cells were hyperplastic. The prepubertal patients showed only diffuse lesions characterized by Sertoli cell hyperplasia, decreased germ cell numbers, and a discontinuous immunoreaction to collagen IV. Conclusions.—The testicular lesions in androgen insensitivity syndrome are probably caused by primary alterations that begin during gestation. These lesions become progressively more pronounced at puberty, when the nodular lesion pattern (adenomas) is completely developed.

Sign in / Sign up

Export Citation Format

Share Document