020. HORMONAL REGULATION OF SPERMATOGENESIS

2010 ◽  
Vol 22 (9) ◽  
pp. 8
Author(s):  
D. Handelsman
Keyword(s):  
Germ Cells ◽  
Sertoli Cells ◽  
Hormonal Regulation ◽  
Intercellular Junctions ◽  
Cell Cytoplasm ◽  
Testicular Cells ◽  
Receptor Knockout Mouse ◽  
Protein Receptors ◽  
Pituitary Secretion ◽  
The Individual

Spermatogenesis is a spatially and temporally co-ordinated proliferation of the germinal epithelium in the semeniferous tubules. The germ cells are embedded in a scafolding formed by adjacent Sertoli cells linked tightly by intercellular junctions and with each germ cell enshrouded by elongations of Sertoli cell cytoplasm. Spermatogenesis comprises serial stages from the mitotic replication of the stem and early germ cells, followed by meiosis, the reductive division producing haploid, amorphous gametes which subsequently undergo spermiogenesis, the metamorphosis into terminally differentiated and functional spermatozoa. Although long known that all but the earliest stages are hormonally regulated by pituitary secretion of LH and FSH, it has remained difficult to separate gonadotrophin effects by classical endocrine ablate-replace methods as these two heterodimeric hormones have identical α and homologous β subunits, are secreted from the same pituitary gonadotrophs to target cognate receptors expressed on adjacent testicular cells as equally homologous, heptahelical G-coupled protein receptors. Over two decades our laboratory has developed a variety of complementary genetic and pharmacological approaches to dissect the individual and co-operative effects of LH, its main effector testosterone and FSH on spermatogenesis. Using the gonadotrophin and testosterone deficient hpg mouse, double transgenic human FSH secreting mouse and the androgen receptor knockout mouse lines together with steroidal depot homone delivery, we have explored systematically annd defined the individual primary actions of FSH and testosterone and their interactions in the regulation of testis growth, spermatogenesis and ultimately male fertility.

scholarly journals N-Cadherin Is Critical for the Survival of Germ Cells, the Formation of Steroidogenic Cells, and the Architecture of Developing Mouse Gonads

Cells ◽  
2019 ◽  
Vol 8 (12) ◽  
pp. 1610 ◽  
Author(s):  
Rafal P. Piprek ◽  
Michal Kolasa ◽  
Dagmara Podkowa ◽  
Malgorzata Kloc ◽  
Jacek Z. Kubiak
Keyword(s):  
Germ Cells ◽  
Hormonal Regulation ◽  
Critical Role ◽  
Somatic Cells ◽  
Gonad Development ◽  
Knock Out ◽  
Gonad Differentiation ◽  
Steroidogenic Cells ◽  
The Individual ◽  
And Function

Normal gonad development assures the fertility of the individual. The properly functioning gonads must contain a sufficient number of the viable germ cells, possess a correct architecture and tissue structure, and assure the proper hormonal regulation. This is achieved by the interplay between the germ cells and different types of somatic cells. N-cadherin coded by the Cdh2 gene plays a critical role in this interplay. To gain an insight into the role of N-cadherin in the development of mouse gonads, we used the Cre-loxP system to knock out N-cadherin separately in two cell lines: the SF1+ somatic cells and the OCT4+ germ cells. We observed that N-cadherin plays a key role in the survival of both female and male germ cells. However, the N-cadherin is not necessary for the differentiation of the Sertoli cells or the initiation of the formation of testis cords or ovigerous cords. In the later stages of gonad development, N-cadherin is important for the maintenance of testis cord structure and is required for the formation of steroidogenic cells. In the ovaries, N-cadherin is necessary for the formation of the ovarian follicles. These results indicate that N-cadherin plays a major role in gonad differentiation, structuralization, and function.

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.

Hormonal regulation of spermatid binding

1991 ◽  
Vol 100 (3) ◽  
pp. 623-633
Author(s):  
D.F. Cameron ◽  
K.E. Muffly
Keyword(s):  
Sertoli Cell ◽  
Sertoli Cells ◽  
Hormonal Regulation ◽  
Unit Area ◽  
Junctional Complex ◽  
Cell Cytoplasm ◽  
Coculture Model ◽  
Ectoplasmic Specialization

A Sertoli-spermatid coculture model is described in which a large percentage (greater than 76%) of round spermatids remain viable for 48 h and bind to Sertoli cells. The effects of follicle-stimulating hormone (FSH) and testosterone on spermatid binding (expressed as the spermatid density; SD = the number of spermatids per unit area of Sertoli cell cytoplasm), ultrastructure of the Sertoli-spermatid junctional complex, and distribution in the Sertoli cell of junction-related F-actin and vinculin are described. Following 48 h of incubation, neither FSH alone nor testosterone alone affected spermatid binding to Sertoli cells beyond that observed in control cocultures. However, the combination of FSH and testosterone (FSH + testosterone) resulted in a significant increase in the density of spermatids bound to Sertoli cells. Junction-related structure of the Sertoli cell cytoskeleton between the Sertoli cell and the pre-step 8 spermatid was different than that observed between the Sertoli cell and the post-step 8 spermatid. The junction-related cytoskeletal modification of the Sertoli cell (JCMS) in the latter was similar in appearance to the well-described ‘Sertoli ectoplasmic specialization’ observed adjacent to post-step 8 spermatids in vivo. FSH + testosterone and FSH alone, but not testosterone alone, resulted in the peripheral distribution of actin and vinculin, which otherwise remained in stress fiber-like structures throughout the Sertoli cell. Results show that maximal spermatid binding to Sertoli cells in vitro requires FSH + testosterone and is associated with the peripheral distribution of actin and vinculin.

Testicular Estrogens and Male Reproduction

Physiology ◽  
2000 ◽  
Vol 15 (4) ◽  
pp. 195-198 ◽  
Author(s):  
Serge Carreau ◽  
Jérôme Levallet
Keyword(s):  
Gene Expression ◽  
Germ Cells ◽  
Hormonal Regulation ◽  
Reproductive Function ◽  
Male Reproduction ◽  
Active Protein ◽  
Widespread Distribution ◽  
Male Reproductive Function ◽  
Testicular Cells ◽  
Estrogen Production

Besides somatic cells, aromatase gene expression and its transduction in an active protein in germ cells provides evidence of an additional site for estrogen production within testes of some mammals. Together with the widespread distribution of estrogen receptors in testicular cells, these data illuminate the hormonal regulation of male reproductive function

The fate of residual bodies and denegrating germ cells and the lipid cycle in sertoli cells in the bandicoot Perameles nasuta Geoffroy (Marsupialia)

1969 ◽  
Vol 17 (5) ◽  
pp. 729 ◽  
Author(s):  
CS Sapsford ◽  
CA Rae ◽  
KW Cleland
Keyword(s):  
Basement Membrane ◽  
Germ Cells ◽  
Sertoli Cells ◽  
The Body ◽  
Residual Body ◽  
Cell Cytoplasm ◽  
Dense Structure ◽  
Main Mass ◽  
Residual Bodies ◽  
New Generation

After separation from mature spermatids, the residual bodies of the bandicoot move within Sertoli cell cytoplasm towards the basement membrane of the tubule. As the result of a reduction in volume and a condensation of its contents, the residual body is transformed into a rather dense structure, the most obvious constituents of which are tightly packed membranous whorls. The particulate lipid of such a body then increases quite markedly, presumably as a consequence of the degradation of the membranous whorls. Surface projections, some of which consist almost exclusively of particulate lipid, develop and subsequently appear to break away from the main mass of the body. Residual bodies of diminishing size and number persist throughout the rest of the seminiferous cycle, conceivably to give rise to lysosome-like organelles which could be utilized in the digestion of a new generation of residual bodies. A characteristic lamellar inclusion present in spermatogonia and spermatocytes permits a distinction to be made between degenerating forms of these cells and most forms of residual bodies. The initiation of the lipid cycle in bandicoot Sertoli cells does not appear to be strictly correlated with the release of lipid from residual bodies.

Sertoli-secreted FGF-2 induces PFKFB4 isozyme expression in mouse spermatogenic cells by activation of the MEK/ERK/CREB pathway

2012 ◽  
Vol 303 (6) ◽  
pp. E695-E707 ◽  
Author(s):  
Marta Gómez ◽  
Anna Manzano ◽  
Agnes Figueras ◽  
Francesc Viñals ◽  
Francesc Ventura ◽  
...  
Keyword(s):  
Gene Expression ◽  
Conditioned Medium ◽  
Cell Lines ◽  
Germ Cells ◽  
Sertoli Cells ◽  
Hormonal Regulation ◽  
Neutralizing Antibodies ◽  
Spermatogenic Cell ◽  
Hormonal Stimulation ◽  
Paracrine Regulation

Sertoli cells play a central role in the control and maintenance of spermatogenesis by secreting growth factors, in response to hormonal stimulation, that participate in the paracrine regulation of this process. In this study, we investigated how the hormonal regulation of spermatogenesis modulates 6-phosphofructo-2-kinase/fructose-2,6-bisphosphatase (PFKFB) isozyme expression in two mouse spermatogenic cell lines, GC-1 spg and GC-2 spd (ts). For this purpose, TM4 Sertoli cells were used to obtain conditioned medium that was treated or not with dihydrotestosterone for 2 days [dihydrotestosterone conditioned medium (TCM) and basal conditioned medium (BCM), respectively]. We observed an increase in the expression of PFKFB4 along with a decrease in PFKFB3 in spermatogenic cell lines treated with TCM. These effects were inhibited by the antiandrogen drug flutamide and by heat-inactivated TCM, indicating the protein nature of the TCM mediator and its dependence on Sertoli cell stimulation by dihydrotestosterone. In addition, adult rat testes treated with the GnRH antagonist Degarelix exhibited a reduction in the expression of PFKFB4 in germ cells. Addition of exogenous FGF-2 mimicked the changes in the Pfkfb gene expression, whereas neutralizing antibodies against FGF-2 abolished them. Interestingly, similar effects on Pfkfb gene expression were observed using different MAPK inhibitors (U-0126, PD-98059, and H-89). Luciferase analysis of Pfkfb4 promoter constructs demonstrated that a putative CRE-binding sequence located at −1,463 relative to the transcription start site is required to control Pfkfb4 gene expression after TCM treatment. Pulldown assays showed the binding of the CREB transcription factor to this site. Altogether, these results show how the paracrine regulation orchestrated by Sertoli cells in response to testosterone controls glycolysis in germ cells.

scholarly journals The rete testis harbors Sertoli-like cells capable of expressing DMRT1

Reproduction ◽  
2019 ◽  
Vol 158 (5) ◽  
pp. 399-413 ◽  
Author(s):  
Ekaterina A Malolina ◽  
Andrey Yu Kulibin
Keyword(s):  
Germ Cells ◽  
Sertoli Cells ◽  
Adult Mouse ◽  
Rete Testis ◽  
Seminiferous Tubules ◽  
Rna Seq ◽  
Supporting Cells ◽  
Testicular Cells ◽  
Qpcr Analysis ◽  
Different Levels

Sertoli cells (SCs) are supporting cells in the mammalian testis that proliferate throughout fetal and postnatal development but exit the cell cycle and differentiate at puberty. In our previous study, we isolated a population of highly proliferative Sertoli-like cells (SLCs) from the region of the adult mouse testis containing the rete testis and adjacent seminiferous tubules. Here RNA-seq of the adult SLC culture as well as qPCR analysis and immunofluorescence of the adult and immature (6 dpp) SLC cultures were performed that allowed us to identify SLC-specific genes, including Pax8, Cdh1, and Krt8. Using these, we found that SLCs are mostly localized in the rete testis epithelium; however, some contribution of transitional zones of seminiferous tubules could not be excluded. The main feature of SLCs indicating their relationship to SCs is DMRT1 expression. More than 40% of both adult and immature SLCs expressed DMRT1 at different levels in culture. Only rare DMRT1+ cells were detected in the adult rete testis, whereas more than 40% of cells were positively stained for DMRT1 in the immature rete testis. One more SC protein, AMH, was found in some rete cells of the immature testis. It was also demonstrated that SLCs expressed such SC genes as Nr5a1, Dhh, Gdnf, and Kitl and interacted with germ cells in 3D co-culture with immature testicular cells. All these similarities between SLCs and rete cells on one the hand and SCs on the other, suggest that rete cells could share a common origin with SCs.

scholarly journals NF-κB-repressed Sirt3 mediates testicular cholesterol metabolism and cytoskeleton assembly via P450scc/SOD2 deacetylation during spermatogenesis

2021 ◽  
Author(s):  
Mei Wang ◽  
Ling Zeng ◽  
Yao Xiong ◽  
Xiao-fei Wang ◽  
Lin Cheng ◽  
...  
Keyword(s):  
Male Infertility ◽  
Germ Cells ◽  
Sertoli Cells ◽  
Male Fertility ◽  
Leydig Cells ◽  
Nuclear Translocation ◽  
Cholesterol Metabolism ◽  
Male Subfertility ◽  
Upstream Regulator ◽  
Testicular Cells

AbstractTesticular homeostasis requires the balanced interplay between specific molecules in Sertoli cells, Leydig cells, germ cells. Loss of this coordination can lead to the disruption of spermatogenesis, even male infertility. By operating the upregulation and downregulation of Sirt3 in our male subfertility rats model and two testicular cells models, we indicated that Sirt3 overexpression and activator ameliorated cholesterol metabolism via P450scc deacetylation in Leydig cells, and cytoskeleton assembly via PDLIM1 with SOD2 deacetylation in Sertoli cells and elongating spermatids. In terms of the upstream regulator of Sirt3, the phosphorylation of NF-κB p65Ser536 stimulated the nuclear translocation of NF-κB subunits (p50, p65, RelB), which bound to TFBS1 and TFBS2 synchronously in the promoter of Sirt3, repressing Sirt3 transcription. This study demonstrates that NF-κB-repressed SIRT3 acts directly on cholesterol metabolism of Leydig cells and cytoskeleton assembly of Sertoli cells via P450scc/SOD2 deacetylation to regulate sperm differentiation, influencing spermatogenesis, even male fertility.Research organism: Rat, mouse

FORMATION IN VITRO OF INTERCELLULAR JUNCTIONS BETWEEN ISOLATED GERM CELLS AND SERTOLI CELLS IN THE RAT

1982 ◽  
Vol 383 (1 The Cell Biol) ◽  
pp. 511-512 ◽  
Author(s):  
E. Ziparo ◽  
G. Siracusa ◽  
F. Palombi ◽  
M. A. Russo ◽  
M. Stefanini
Keyword(s):  
Germ Cells ◽  
Sertoli Cells ◽  
Intercellular Junctions
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