scholarly journals Gas6 and the Tyro 3 receptor tyrosine kinase subfamily regulate the phagocytic function of Sertoli cells

Reproduction ◽  
2008 ◽  
Vol 135 (1) ◽  
pp. 77-87 ◽  
Author(s):  
Weipeng Xiong ◽  
Yongmei Chen ◽  
Huizhen Wang ◽  
Haikun Wang ◽  
Hui Wu ◽  
...  

The apoptotic spermatogenic cells and residual bodies are phagocytosed and degraded by Sertoli cells during spermatogenesis. The mechanisms of this process are largely unknown. Here, we demonstrate that Gas6 and its receptors, the Tyro 3 subfamily of receptor tyrosine kinases (RTKs; Tyro 3, Axl, and Mer), regulate the phagocytic function of Sertoli cells. The phagocytic ability of Sertoli cells increased by five times in the presence of Gas6 in serum-free medium when compared with controls. The Sertoli cells lacking Mer showed a 35% reduction in phagocytosis of apoptotic spermatogenic cells when compared with wild-type (WT) controls, whereas the Sertoli cells lacking Tyro 3 or Axl exhibited phagocytic activity comparable with the controls. Notably, the Sertoli cells lacking all three members of the Tyro 3 RTK subfamily showed a dramatic decrease in phagocytic ability of 7.6-fold when compared with WT Sertoli cells. The deficiency in phagocytosis by the triple-mutant Sertoli cells was due to the deficit in binding of the Sertoli cells to apoptotic germ cells. These findings suggest that Mer is responsible for triggering phagocytosis of apoptotic spermatogenic cells by Sertoli cells and that Tyro 3, Axl, and Mer participate in recognizing and binding apoptotic germ cells by Sertoli cells in a redundant manner. Gas6 is a functional ligand of the Tyro 3 RTK subfamily in mediating phagocytic ability of Sertoli cells.

Reproduction ◽  
2009 ◽  
Vol 138 (4) ◽  
pp. 655-666 ◽  
Author(s):  
Yongmei Chen ◽  
Huizhen Wang ◽  
Nan Qi ◽  
Hui Wu ◽  
Weipeng Xiong ◽  
...  

Mice lacking TYRO3, AXL and MER (TAM) receptor tyrosine kinases (RTKs) are male sterile. The mechanism of TAM RTKs in regulating male fertility remains unknown. In this study, we analyzed in more detail the testicular phenotype of TAM triple mutant (TAM−/−) mice with an effort to understand the mechanism. We demonstrate that the three TAM RTKs cooperatively regulate male fertility, and MER appears to be more important than AXL and TYRO3. TAM−/− testes showed a progressive loss of germ cells from elongated spermatids to spermatogonia. Young adult TAM−/− mice exhibited oligo-astheno-teratozoospermia and various morphological malformations of sperm cells. As the mice aged, the germ cells were eventually depleted from the seminiferous tubules. Furthermore, we found that TAM−/− Sertoli cells have an impaired phagocytic activity and a large number of differentially expressed genes compared to wild-type controls. By contrast, the function of Leydig cells was not apparently affected by the mutation of TAM RTKs. Therefore, we conclude that the suboptimal function of Sertoli cells leads to the impaired spermatogenesis in TAM−/− mice. The results provide novel insight into the mechanism of TAM RTKs in regulating male fertility.


2015 ◽  
Vol 2015 ◽  
pp. 1-8 ◽  
Author(s):  
Vincenza Ciaramella ◽  
Rosanna Chianese ◽  
Paolo Pariante ◽  
Silvia Fasano ◽  
Riccardo Pierantoni ◽  
...  

Hypothalamic Gonadotropin Releasing Hormone (GnRH),viaGnRH receptor (GnRHR), is the main actor in the control of reproduction, in that it induces the biosynthesis and the release of pituitary gonadotropins, which in turn promote steroidogenesis and gametogenesis in both sexes. Extrabrain functions of GnRH have been extensively described in the past decades and, in males, local GnRH activity promotes the progression of spermatogenesis and sperm functions at several levels. The canonical localization ofGnrh1andGnrhr1mRNA is Sertoli and Leydig cells, respectively, but ligand and receptor are also expressed in germ cells. Here, we analysed the expression rate ofGnrh1andGnrhr1in rat testis (180 days old) by quantitative real-time PCR (qPCR) and byin situhybridization we localizedGnrh1andGnrhr1mRNA in different spermatogenic cells of adult animals. Our data confirm the testicular expression ofGnrh1and ofGnrhr1in somatic cells and provide evidence that their expression in the germinal compartment is restricted to haploid cells. In addition, not only Sertoli cells connected to spermatids in the last steps of maturation but also Leydig and peritubular myoid cells expressGnrh1.


2012 ◽  
Vol 36 (0E) ◽  
pp. 248-253
Author(s):  
AL-Samarrae N. S.

The seminiferous epithelium of the testes of cat consists of two groups of cells; Spermatogenic cells and Sertoli cells. The interstitial areas are filled with Leydic cells, blood and lymph vessels, and connective tissue. Germ cells in the Spermatogenic process of the testis of cat can be classified into ten steps, based on the pattern degree of nuclear chromatin condensation. Primary spermatogonia contain large spherical nuclei with mostly euchromatin. Spermatogonia proliferate to give rise to spermatogonia type –A; Intermediate or type-I spermatogonia, and spermatogonia type-B. Type–B spermatogonia yield primary spermatocyte at the end of mitosis. The primary spermatocyte is transformed into secondary spermatocyte during meiosis I. These cells are converted into spermatid during meiosis II. Metamorphosis of spermatids shows: Golgi step, Cap step, Acrosomal step, Maturation step.


PLoS Genetics ◽  
2021 ◽  
Vol 17 (9) ◽  
pp. e1009778
Author(s):  
Bo Chen ◽  
Gengzhen Zhu ◽  
An Yan ◽  
Jing He ◽  
Yang Liu ◽  
...  

Meiosis initiation and progression are regulated by both germ cells and gonadal somatic cells. However, little is known about what genes or proteins connecting somatic and germ cells are required for this regulation. Our results show that deficiency for adhesion molecule IGSF11, which is expressed in both Sertoli cells and germ cells, leads to male infertility in mice. Combining a new meiotic fluorescent reporter system with testicular cell transplantation, we demonstrated that IGSF11 is required in both somatic cells and spermatogenic cells for primary spermatocyte development. In the absence of IGSF11, spermatocytes proceed through pachytene, but the pericentric heterochromatin of nonhomologous chromosomes remains inappropriately clustered from late pachytene onward, resulting in undissolved interchromosomal interactions. Hi-C analysis reveals elevated levels of interchromosomal interactions occurring mostly at the chromosome ends. Collectively, our data elucidates that IGSF11 in somatic cells and germ cells is required for pericentric heterochromatin dissociation during diplotene in mouse primary spermatocytes.


2018 ◽  
Vol 30 (1) ◽  
pp. 211
Author(s):  
N. A. Volkova ◽  
A. N. Vetokh ◽  
I. P. Novgorodova ◽  
A. V. Dotsev ◽  
N. A. Zinovieva

Male gonads are valuable genetic material for creation of biomaterial cryobanks to preserve the genes of various animals, including poultry. Spermatogonia, which are stem cells of the testes, are of greatest interest. For effective selection of spermatogenic cells, including spermatogonia, it is necessary to know the specific features of spermatogenesis of the species of interest. In this regard, the aim of this study was to investigate the dynamics of spermatogenesis in guinea fowl. Histological examinations of guinea fowl testes (n = 90 birds) were done for 9 age categories, from 2 wk to 6 months. For each individual, at least 30 seminiferous tubules were examined. Seminiferous tubule diameters and numbers and types of spermatogenic cells (based on morphology) were determined. Overall, the histologic structure of guinea fowl testes was similar to that of mammals. Cell populations of the seminiferous tubules included Sertoli cells and generative cells, including spermatogonia, spermatocytes, spermatids, and sperm, at various stages of differentiation. Diameter of seminiferous tubules was (mean ± SEM) 36 ± 1, 58 ± 1, 64 ± 1, 65 ± 1, 110 ± 3, 178 ± 4, 233 ± 4, 274 ± 6, and 295 ± 5 µm at 2 wk, 1, 1.5, 2, 2.5, 3, 4, 5, and 6 months, respectively. Furthermore, at those ages, the number of spermatogenic cells per tubule was 18 ± 1, 20 ± 1, 29 ± 2, 30 ± 2, 68 ± 5, 114 ± 8, 186 ± 10, 400 ± 20, and 447 ± 24. Maximum percentage of spermatogonia was 72 ± 2% at 6 wk. Primary and secondary spermatocytes were first observed at 10 and 12 wk of age, respectively, whereas spermatids were first apparent at 4 months. Sperm were first identified at 5 months, with more present at 6 months. We concluded that the optimal age for retrieving testicular germ cells in guinea fowl was no later than 8 wk, as that represented the age when seminiferous tubules were dominated by spermatogonia. The study was supported by the Russian Science Foundation (Project no.16-16-04104).


2020 ◽  
Vol 98 (Supplement_4) ◽  
pp. 373-373
Author(s):  
Tatyana Kotova ◽  
Anastasia N Vetokh ◽  
Ludmila A Volkova ◽  
Natalia Volkova ◽  
Natalia A Zinovieva

Abstract The use of testicular stem cells (spermatogonia) is of most interest for obtaining individuals with predetermined traits and genome genetic modification and for conservation of poultry gene pool. A significant population of mature donor germ cells (sperm) is formed upon successful spermatogonia cells transplantation into the testes of male recipients. Obtained sperm can be used to produce offspring with the desired traits. A key step in this technology is the removal of own spermatogenic cells (inhibition of spermatogenesis) in male recipients. The aim of research was to develop and optimize methodological approaches to inhibit the spermatogenesis in quail using busulfan. This drug was injected directly into the testes parenchyma of mature males by multiple injection at the concentration from 20 to 100 mg per 1kg of body weight (n = 25). Histological preparations of testes from the experimental quails were obtained to study composition of spermatogenic cells in the seminiferous tubules after busulfan administration. The male peers who were not injected with busulfan were used as a control. Experimental quails showed a decrease in the number of spermatogenic cells in the seminiferous tubules 32, 75, 111, 119 and 118 times compared with the control when using busulfan in concentrations 20, 40, 60, 80 and 100 mg/kg of weight, respectively (P < 0.001). The cells composition in the seminiferous tubules from experimental quails was represented mainly by Sertoli cells and spermatogonia. After busulfan introduction at the concentrations 20, 40, 60, 80 and 100 mg/kg, the percentage of spermatogonia was 55±5 %, 24±4 %, 6±2 %, 5±2 % and 4±1 %, respectively. The use of busulfan at the concentration of 80–100 mg/kg led to high mortality of quails. Thus, it was found that the optimal busulfan concentration for elimination of quail spermatogenic cells was 60 mg/kg. Supported by RFBR within Project №18-29-07079.


2019 ◽  
Vol 97 (Supplement_3) ◽  
pp. 373-373
Author(s):  
Anastasia N Vetokh ◽  
Natalia A Volkova ◽  
Evgeniya K Tomgorova ◽  
Ludmila A Volkova ◽  
Natalia A Zinovieva

Abstract The cells of the male gonads are considered as a valuable genetic material for the conservation of the gene pool of breeds and lines of agricultural birds, as well as the directed modification of the poultry genome. Mature germ cells – spermatozoa and their predecessors – spermatogonia, spermatocytes and spermatids can be used for these purposes. To obtain these types of cells, it is necessary to know the characteristics of their development (spermatogenesis). The dynamics of the development of certain spermatogenic cell types in the testicular tubules of different-aged roosters has been studied. Histological studies were performed on testes of roosters aged from 1 week to 6 months with an interval of 2 weeks. Samples of testis tissue were fixed in Bouin’s solution. Histological sections were stained with hematoxylin-eosin. Identification of different cell types (Sertoli, spermatogonia, spermatocytes, spermatids, sperm cells) was carried out according to their morphology. At the age of 1–6 weeks in the seminiferous tubule of roosters, the mainly presence of two cell types was noted: Sertoli cells and spermatogonia. From 7 weeks of age, spermatocytes were detected in the seminiferous tubules, in the 4 months - spermatids, in the 5.5 months - sperm cells. The number of Sertoli cells remained almost unchanged with age and was 21 ± 2. The percentage of these cells decreased with age from 71 ± 3 % to 5 ± 1 %. The percentage of spermatogonia also decreased with age from 75 ± 2 % to 7 ± 1 %. The number of spermatids and spermatozoa, on the contrary, increased to puberty (6 months) and reached 54 %. The study was supported by the RFBR within Project no.18-29-07079.


2004 ◽  
Vol 16 (9) ◽  
pp. 278
Author(s):  
S. H. S. Mendis ◽  
S. Meachem ◽  
C. Brown ◽  
K. L. Loveland

Activin is a member of the TGF β (Transforming Growth Factor β) superfamily of ligands which influence many aspects of male germ cell development. Formed by the linkage of two common β subunits, activin A (a βA βA dimer) has been reported to (1) cause apoptosis of primodial germ cells, (2) inhibit the cellular transition of gonocytes into undifferentiated spermatogonia, and (3) enhance FSH-mediated stimulation of Sertoli cell proliferation in the newborn rat testis. Although closely related, activin βA and activin βB (a βB:βB dimer) differ in that activin βB is less bioactive. In this study we examined the role of activin during the first wave of spermatogenesis using knockout (Inhba–/–) and transgenic (InhbaBK/BK; two copies of the βB subunit gene coding sequence replace the βA coding sequence) mouse models with reduced levels of bioactive activin. Absolute gonocyte and Sertoli cell numbers were significantly elevated in the absence of activin A in newborn Inhba–/– testes compared to wild type, as determined by optical disector analysis. As the Inhba–/– mice die at birth, we next studied the BK/BK mice to examine postnatal effects of reduced activin bioactivity. Surprisingly, both body weight and testis weight were lower in the BK/BK compared to wild type mice at Day 7 and 14, but testis growth in proportion to body weight was significantly reduced between 7 and 14 days. At 2 weeks of age, the BK/BK animal displays a significant reduction in Sertoli cells and specific subpopulations of germ cells, the latter of which was evident only in heterozygote animals. Examination of these two models has identified that lower levels of bioactive activin affect Sertoli cells and germ cells at different stages of testicular development. Our ongoing studies involving RNA analyses of various candidate target genes will facilitate a greater understanding of the molecular basis for these observations.


Author(s):  
Rita Meyer ◽  
Zoltan Posalaky ◽  
Dennis Mcginley

The Sertoli cell tight junctional complexes have been shown to be the most important structural counterpart of the physiological blood-testis barrier. In freeze etch replicas they consist of extensive rows of intramembranous particles which are not only oriented parallel to one another, but to the myoid layer as well. Thus the occluding complex has both an internal and an overall orientation. However, this overall orientation to the myoid layer does not seem to be necessary to its barrier function. The 20 day old rat has extensive parallel tight junctions which are not oriented with respect to the myoid layer, and yet they are inpenetrable by lanthanum. The mechanism(s) for the control of Sertoli cell junction development and orientation has not been established, although such factors as the presence or absence of germ cells, and/or hormones, especially FSH have been implicated.


Author(s):  
J. Chakraborty ◽  
A. P. Sinha Hikim ◽  
J. S. Jhunjhunwala

Although the presence of annulate lamellae was noted in many cell types, including the rat spermatogenic cells, this structure was never reported in the Sertoli cells of any rodent species. The present report is based on a part of our project on the effect of torsion of the spermatic cord to the contralateral testis. This paper describes for the first time, the fine structural details of the annulate lamellae in the Sertoli cells of damaged testis from guinea pigs.One side of the spermatic cord of each of six Hartly strain adult guinea pigs was surgically twisted (540°) under pentobarbital anesthesia (1). Four months after induction of torsion, animals were sacrificed, testes were excised and processed for the light and electron microscopic investigations. In the damaged testis, the majority of seminiferous tubule contained a layer of Sertoli cells with occasional spermatogonia (Fig. 1). Nuclei of these Sertoli cells were highly pleomorphic and contained small chromatinic clumps adjacent to the inner aspect of the nuclear envelope (Fig. 2).


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