scholarly journals Retinoic acid metabolism links the periodical differentiation of germ cells with the cycle of Sertoli cells in mouse seminiferous epithelium

2012 ◽  
Vol 128 (11-12) ◽  
pp. 610-624 ◽  
Author(s):  
Ryo Sugimoto ◽  
Yo-ichi Nabeshima ◽  
Shosei Yoshida
Author(s):  
M. Dym

The Sertoli cells perform an impressive array of functions in the testis. It is possible that the full control of germ cell differentiation is mediated by this elaborate cell type (Fig. 1). On the basis of its shape and strategic position within the seminiferous epithelium the functions of (1) support and nutrition have been assigned. Fawcett and Phillips (J. Reprod. Fert. 6: 405, 1969) demonstrated that the Sertoli cells engineer the (2) release of late spermatids into the tubule lumen; other data suggest that they are instrumental in the migration of the germ cells from the basal lamina to the lumen. Tight junctions between adjacent Sertoli cells subdivide the seminiferous epithelium into two compartments, basal and adluminal. These junctions form the (3) morphological basis of the blood-testis barrier . The Sertoli cells are capable of (4) phagocytizing vast numbers of degenerating germ cells and sperm residual bodies.


2010 ◽  
Vol 365 (1546) ◽  
pp. 1593-1605 ◽  
Author(s):  
Ilona A. Kopera ◽  
Barbara Bilinska ◽  
C. Yan Cheng ◽  
Dolores D. Mruk

Spermatogenesis is a process that involves an array of cellular and biochemical events, collectively culminating in the formation of haploid spermatids from diploid precursor cells known as spermatogonia. As germ cells differentiate from spermatogonia into elongated spermatids, they also progressively migrate across the entire length of the seminiferous epithelium until they reach the luminal edge in anticipation of spermiation at late stage VIII of spermatogenesis. At the same time, these germ cells must maintain stable attachment with Sertoli cells via testis-unique intermediate filament- (i.e. desmosome-like junctions) and actin- (i.e. ectoplasmic specializations, ESs) based cell junctions to prevent sloughing of immature germ cells from the seminiferous epithelium, which may result in infertility. In essence, both desmosome-like junctions and basal ESs are known to coexist between Sertoli cells at the level of the blood–testis barrier where they cofunction with the well-studied tight junction in maintaining the immunological barrier. However, the type of anchoring device that is present between Sertoli and germ cells depends on the developmental stage of the germ cell, i.e. desmosome-like junctions are present between Sertoli and germ cells up to, but not including, step 8 spermatids after which this junction type is replaced by the apical ES. While little is known about the biology of the desmosome-like junction in the testis, we have a relatively good understanding of the molecular architecture and the regulation of the ES. Here, we discuss recent findings relating to these two junction types in the testis, highlighting prospective areas that should be investigated in future studies.


2019 ◽  
Vol 100 (6) ◽  
pp. 1648-1660 ◽  
Author(s):  
Sadman Sakib ◽  
Aya Uchida ◽  
Paula Valenzuela-Leon ◽  
Yang Yu ◽  
Hanna Valli-Pulaski ◽  
...  

Abstract Three-dimensional (3D) organoids can serve as an in vitro platform to study cell–cell interactions, tissue development, and toxicology. Development of organoids with tissue architecture similar to testis in vivo has remained a challenge. Here, we present a microwell aggregation approach to establish multicellular 3D testicular organoids from pig, mouse, macaque, and human. The organoids consist of germ cells, Sertoli cells, Leydig cells, and peritubular myoid cells forming a distinct seminiferous epithelium and interstitial compartment separated by a basement membrane. Sertoli cells in the organoids express tight junction proteins claudin 11 and occludin. Germ cells in organoids showed an attenuated response to retinoic acid compared to germ cells in 2D culture indicating that the tissue architecture of the organoid modulates response to retinoic acid similar to in vivo. Germ cells maintaining physiological cell–cell interactions in organoids also had lower levels of autophagy indicating lower levels of cellular stress. When organoids were treated with mono(2-ethylhexyl) phthalate (MEHP), levels of germ cell autophagy increased in a dose-dependent manner, indicating the utility of the organoids for toxicity screening. Ablation of primary cilia on testicular somatic cells inhibited the formation of organoids demonstrating an application to screen for factors affecting testicular morphogenesis. Organoids can be generated from cryopreserved testis cells and preserved by vitrification. Taken together, the testicular organoid system recapitulates the 3D organization of the mammalian testis and provides an in vitro platform for studying germ cell function, testicular development, and drug toxicity in a cellular context representative of the testis in vivo.


Reproduction ◽  
2011 ◽  
Vol 141 (5) ◽  
pp. 571-580 ◽  
Author(s):  
Ka-Wai Mok ◽  
Dolores D Mruk ◽  
Pearl P Y Lie ◽  
Wing-Yee Lui ◽  
C Yan Cheng

Adjudin is a derivative of 1H-indazole-3-carboxylic acid that was shown to have potent anti-spermatogenic activity in rats, rabbits, and dogs. It exerts its effects most notably locally in the apical compartment of the seminiferous epithelium, behind the blood–testis barrier, by disrupting adhesion of germ cells, most notably spermatids to the Sertoli cells, thereby inducing release of immature spermatids from the epithelium that leads to infertility. After adjudin is metabolized, the remaining spermatogonial stem cells and spermatogonia repopulate the seminiferous epithelium gradually via spermatogonial self-renewal and differentiation, to be followed by meiosis and spermiogenesis, and thus fertility rebounds. Recent studies in rats have demonstrated unequivocally that the primary and initial cellular target of adjudin in the testis is the apical ectoplasmic specialization, a testis-specific anchoring junction type restricted to the interface between Sertoli cells and elongating spermatids (from step 8 to 19 spermatids). In this review, we highlight some of the recent advances and obstacles regarding the possible use of adjudin as a male contraceptive.


2007 ◽  
Vol 1120 (1) ◽  
pp. 114-130 ◽  
Author(s):  
T. J. DOYLE ◽  
K. W. BRAUN ◽  
D. J. MCLEAN ◽  
R. W. WRIGHT ◽  
M. D. GRISWOLD ◽  
...  

Author(s):  
Rachel L Gewiss ◽  
Nathan C Law ◽  
Aileen R Helsel ◽  
Eric A Shelden ◽  
Michael D Griswold

Abstract Sertoli cells are a critical component of the testis environment for their role in maintaining seminiferous tubule structure, establishing the blood-testis barrier, and nourishing maturing germ cells in a specialized niche. This study sought to uncover how Sertoli cells are regulated in the testis environment via germ cell crosstalk in the mouse. We found two major clusters of Sertoli cells as defined by their transcriptomes in Stages VII–VIII of the seminiferous epithelium and a cluster for all other stages. Additionally, we examined transcriptomes of germ cell-deficient testes and found that these existed in a state independent of either of the germ cell-sufficient clusters. Altogether, we highlight two main transcriptional states of Sertoli cells in an unperturbed testis environment, and a germ cell-deficient environment does not allow normal Sertoli cell transcriptome cycling and results in a state unique from either of those seen in Sertoli cells from a germ cell-sufficient environment.


2005 ◽  
Vol 17 (9) ◽  
pp. 70
Author(s):  
M. P. Hedger

Spermatogenesis is a complex yet highly organised process involving intimate interactions between the supporting Sertoli cells and germ cells at various stages of development. The repeating pattern of the cycle of the seminiferous epithelium is due to the fact that spermatogonia enter spermatogenesis at regularly spaced intervals and proceed through the process at a species-specific rate. How this degree of coordination is maintained remains poorly understood, but recent evidence has focussed attention on the role of growth factors produced by the Sertoli cells and germ cells. Several of these growth factors, such as interleukin-1α (IL-1α), IL-6, tumour necrosis factor (TNFα) and activin A, are also inflammatory cytokines. This has led some researchers to question the physiological significance of these data with respect to normal testicular function. For example, in spite of the fact that IL-1α is produced by the Sertoli cell and regulates spermatogonial proliferation and development in vitro, mice lacking the IL-1R, and hence unresponsive to IL-1α, possess relatively normal fertility. So what role, if any, do these cytokines play in the normal testis, or are they only important during inflammation? It is quite evident that these cytokines have stimulatory and/or inhibitory effects on spermatogonial and spermatocyte development. These cytokines also interact at multiple levels within each other’s signalling pathways and have considerable redundancy of action. Moreover, expression of these cytokines varies across the cycle of the seminiferous epithelium, with major changes in production coinciding with two key events within the cycle: the release of sperm from the epithelium, and the major peaks of DNA synthesis by spermatogonia and preleptotene spermatocytes. It is therefore possible to hypothesise that release of sperm and resorption of the residual cytoplasm triggers a self-regulating inflammatory cascade within the epithelium that initiates and then modulates the next round of spermatogenic development, ensuring that spermatogonia enter the process at the appropriately spaced intervals.


Reproduction ◽  
2018 ◽  
Author(s):  
Valeria Merico ◽  
Juan Pablo Luaces ◽  
Luis F. Rossi ◽  
Paola Rebuzzini ◽  
Maria Susana Merani ◽  
...  

In Nature, mammalian seasonal breeders undergo spermatogenetic arrest during the non-breeding season. In the large hairy armadillo Chaetophractus villosus, testis regression initiates with immature post-meiotic germ cells sloughing into the tubule lumen and continues with the death of the remaining spermatocytes. At the end of the regression period, only spermatogonia and Sertoli cells persist in the seminiferous epithelium. It has been suggested that cell sloughing is determined by changes in the adhesion complexes between Sertoli cells and spermatids, which are mediated by low intra-testicular testosterone levels. By immunofluorescence and western blotting we studied key proteins of the N-cadherin/N-cadherin and α6β1-integrin/laminin interlocks that contribute to the complex Sertoli/spermatid adhesion system throughout the eight stages of the seminiferous epithelium cycle in the comparison between active and regressing testes. In active testis, β1-integrin, Laminin G3, N-cadherin, β-catenin, P-β-catenin-Tyr654, FAK, P-FAK-Tyr397, Src, P-Src-Tyr416 proteins present a spermatogenetic cycle-dependent localization pattern, unmaintained in regressing testes. In the latter, quantitative variations and changes in the phosphorylation state of protein FAK, Src, and β-catenin contribute to the disassembly of the N-cadherin/N-cadherin and α6β1-integrin/laminin interlocks, thus promoting the massive release of immature spermatids.


2021 ◽  
Vol 37 ◽  
pp. e37035
Author(s):  
Fernanda Carolina Ribeiro Dias ◽  
Jullyana Costa Machado ◽  
Sérgio Luis Pinto da Matta ◽  
Angelica de Oliveira Gomes ◽  
Marcos de Lucca Moreira Gomes

Many studies have been trying to establish standard protocols for animal experimentation, especially for animal species or strains, to master research variables with high precision. The main mouse strains used in the field of the biology of reproduction are Swiss, Balb/c, and C57BL/6. Since some of the strains show reproduction limitations, such as the size of the litter, the present study aimed to compare their spermatogenic processes to verify differences regarding the testicular parenchyma and germ cell populations, which could explain low offspring production. In addition, the present study provides additional information concerning the testicular parenchyma of such strains, which consequently would help researchers to choose the most suitable strain for reproductive studies. Six adult male mice were used for each of the strains. After euthanasia, the testes were weighed, fixated with Karnovsky fixative, embedded in methacrylate, sectioned, and stained with toluidine blue/sodium borate 1%. Morphometrical analyses from the testicular parenchyma (seminiferous tubules and interstitium) were made using the software ImageJ. Germ and Sertoli cells populations were counted in seminiferous tubules cross-sections at stage I of the seminiferous epithelium cycle. The lowest body and testicular weights were observed in C57BL/6 animals, followed by Balb/c and Swiss, however, the relative testes, parenchyma, and albuginea weights were significantly lower only in C57BL/6. Despite the seminiferous tubules and seminiferous epithelium proportions were lower in Swiss animals, their relative amount related to the body weight was the same among strains. The total number of germ cells was higher in Swiss animals, reflecting higher spermatogenic yield and daily sperm production. Due to the lower relative number of Sertoli cells, the Swiss animals showed the highest Sertoli cell index and support capacity. On the other hand, the lowest pathological indexes regarding the germ cells were observed in Balb/c animals, followed by Swiss and C57BL/6. In the interstitium, the proportion of blood vessels was lower in Swiss mice, while the lymphatic cell proportion was lower in C57BL/6 animals. Moreover, the highest proportions of Leydig cells and macrophages were noticed in Swiss mice, which may indicate increased testosterone levels. Altogether, such observations must be taken into account when choosing any of the studied strains for reproduction studies.


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