Regulation by pH of the Alternative Splicing of the Stem Cell Factor Pre-mRNA in the Testis (original) (raw)
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EC ENDOCRINOLOGY AND METABOLIC RESEARCH , 2017
Spermatogenesis is the biological process that generates male gametes for the transfer of the paternal chromosomes to the oo-cytes, at the time of fertilization. Neuroendocrine hormones work in tandem with testicular genes to bring about the maturation of the male gamete or spermatozoon. While some of the genes involved in the differentiation of spermatozoa are well known others are 'not so obvious'. The aim of this article is to conceptualize the molecular pathway(s) through which the 'not so obvious' Sertoli cell 'mediators' communicate with germ cells for their differentiation within the seminiferous tubules of the mammalian testes.
Hormonal control of Sertoli cell metabolism regulates spermatogenesis
Cellular and Molecular Life Sciences, 2013
Hormonal regulation is essential to spermatogenesis. Sertoli cells (SCs) have functions that reach far beyond the physical support of germ cells, as they are responsible for creating the adequate ionic and metabolic environment for germ cell development. Thus, much attention has been given to the metabolic functioning of SCs. During spermatogenesis, germ cells are provided with suitable metabolic substrates, in a set of events mediated by SCs. Multiple signaling cascades regulate SC function and several of these signaling pathways are hormone-dependent and cell-specific. Within the seminiferous tubules, only SCs possess receptors for some hormones rendering them major targets for the hormonal signaling that regulates spermatogenesis. Although the mechanisms by which SCs fulfill their own and germ cells metabolic needs are mostly studied in vitro, SC metabolism is unquestionably a regulation point for germ cell development and the hormonal control of these processes is required for a normal spermatogenesis.
Methods in molecular biology (Clifton, N.J.), 2018
Sertoli cells play a central role in spermatogenesis. They maintain the blood-testis barrier, an essential feature of seminiferous tubules which creates the proper environment for the occurrence of the spermatogenesis. However, this confinement renders germ cells almost exclusively dependent on Sertoli cells' nursing function and support. Throughout spermatogenesis, differentiating sperm cells become more specialized, and their biochemical machinery is insufficient to meet their metabolic demands. Although the needs are not the same at all differentiation stages, Sertoli cells are able to satisfy their needs. In order to maintain the seminiferous tubule energetic homeostasis, Sertoli cells react in response to several metabolic stimuli, through signaling cascades. The AMP-activated kinase, sensitive to the global energetic status; the hypoxia-inducible factors, sensitive to oxygen concentration; and the peroxisome proliferator-activated receptors, sensitive to fatty acid availab...
50 years of spermatogenesis: Sertoli cells and their interactions with germ cells
Biology of Reproduction, 2018
The complex morphology of the Sertoli cells and their interactions with germ cells has been a focus of investigators since they were first described by Enrico Sertoli. In the past 50 years, information on Sertoli cells has transcended morphology alone to become increasingly more focused on molecular questions. The goal of investigators has been to understand the role of the Sertoli cells in spermatogenesis and to apply that information to problems relating to male fertility. Sertoli cells are unique in that they are a nondividing cell population that is active for the reproductive lifetime of the animal and cyclically change morphology and gene expression. The numerous and distinctive junctional complexes and membrane specializations made by Sertoli cells provide a scaffold and environment for germ cell development. The increased focus of investigators on the molecular components and putative functions of testicular cells has resulted primarily from procedures that isolate specific ...
Molecular Reproduction and Development, 1997
To better understand the molecular interactions between somatic and germ cells in the mammalian testis, we have begun to analyze with mRNA differential display changes in gene expression induced by coculturing rat Sertoli cells and germ cells. We have identified 10 cDNAs that are either downregulated or up-regulated in cocultures of germ cells and Sertoli cells. Three genes expressed in Sertoli cells and three genes expressed in germ cells were downregulated in Sertoli cell-germ cell cocultures, whereas four genes were up-regulated in the cocultures. Northern blot analysis was used to establish the expression pattern of the mRNAs encoded by the cDNAs and to define the sizes of the differentially expressed mRNAs. Sequence analysis of the cDNAs and computer searches against the GenBank and EMBL DNA databases were used to relate the ten cDNAs to known genes. Of the three Sertoli cell cDNAs, one appeared identical to transferrin, while the other two shared regions of similarity to an endoplasmic reticulum stress protein and to a pro-a 2 XI collagen, respectively. The three germ cell cDNAs shared sequences with fibronectin, with a basic fibroblast growth factor receptor and with an IgG gamma 2b, respectively. The four cDNAs that were up-regulated in the Sertoli-germ cell cocultures showed similarity to an isoform of casein kinase 1d, to an epidermal growth factor, to a statin-related protein, and to an integral membrane glycoprotein. These data demonstrate that a number of specific genes are up-and down-regulated when germ cells and Sertoli cells are cocultured, and suggest these genes are important in cell to cell communication during spermatogenesis.
Stem Cell Investigation
Background: The complex process of spermatogenesis is regulated by various factors. Several studies have been conducted to proliferate cells involved in the spermatogenesis process, in culture by used growth factors, different hormones and feeder cells. This study was conducted to evaluate the role of Sertoli cells on gene expression of fibroblast growth factor (FGF2) and glial cell derived neurotrophic factor (GDNF) after removal of spermatogonial stem cells (SSCs) from the culture medium. Methods: Following isolation, bovine SSCs were co-cultured with Sertoli cells and follicular stimulating hormone (FSH) for 12 days. In the treatment group, SSCs were removed from the culture medium; in the control group no intervention was done in the culture. Colony formation of SSCs was evaluated by using an inverted microscope. Then, the expression of factors genes were assessed by quantitative RT-PCR. Data was analyzed by using paired-samples t-test. Results: The results showed that removal of SSCs led to the increase in expression of GDNF and FGF2. These findings suggest that loss of SSCs population or decline in its population leads to changing in behavior of somatic cells which forming niche and consequently stimulates self-renewal and inhibits differentiation of SSCs. Conclusions: The present study showed that removal of SSCs from the culture medium could be a model for damage to SSCs; the results revealed that niche cells respond to SSCs removal by upregulation of FGF2 and GDNF to stimulate self-renewal of SSCs and abrogation of differentiation.
Origin and function of embryonic Sertoli cells
BioMolecular Concepts, 2011
In 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 geneSRYin pre-SCs initiates a ...
Molecular endocrinology (Baltimore, Md.), 2015
Sertoli cells (SCs), the only somatic cells within seminiferous tubules, associate intimately with developing germ cells. They not only provide physical and nutritional support but also secrete factors essential to the complex developmental processes of germ cell proliferation and differentiation. The SC transcriptome must therefore adapt rapidly during the different stages of spermatogenesis. We report comprehensive genome-wide expression profiles of pure populations of SCs isolated at 5 distinct stages of the first wave of mouse spermatogenesis, using RNA sequencing technology. We were able to reconstruct about 13 901 high-confidence, nonredundant coding and noncoding transcripts, characterized by complex alternative splicing patterns with more than 45% comprising novel isoforms of known genes. Interestingly, roughly one-fifth (2939) of these genes exhibited a dynamic expression profile reflecting the evolving role of SCs during the progression of spermatogenesis, with stage-speci...
The second messenger pathway for germ cell-mediated stimulation of Sertoli cells
Biochemical and Biophysical Research Communications, 1992
Treatment of cultured rat Sertoli cells with FSH or dibutyryl CAMP for 30 min resulted in phosphorylation of the same Sertoli cell proteins. Different Sertoli cell proteins were phosphorylated after calcium ionophore A23187 and 12-0-tetradecanoylphorbol-13acetate (TPA) treatment. A23187 stimulated the phosphorylation of hsp27, while TPA alone had no effect. TPA plus A23187 resulted in phosphorylation of a 14 kDa protein, in addition to hsp27. The effect of TPA plus A23187 was identical to that of germ cells on Sertoli cell protein phosphorylation. FSH-stimulated CAMP production by Sertoli cells was reduced by prior exposure of Sertoli cells to germ cells. The results indicate that germ cells stimulate Sertoli cells by the inositol trisphosphate/diacylglycerol mediated second messenger pathway. The results also suggest that the germ cell-activated pathway interacts within Sertoli cells to modulate Sertoli cell response to FSH.
Novel molecular mechanisms involved in hormonal regulation of lactate production in Sertoli cells
Reproduction, 2015
The aim of the study was to analyze molecular mechanisms involved in FSH and basic fibroblast growth factor (bFGF) regulation of lactate production in rat Sertoli cells. The regulation of the availability of pyruvate, which is converted to lactate, could be a mechanism utilized by hormones to ensure lactate supply to germ cells. On one hand, the regulation of 6-phosphofructo-2-kinase/fructose-2,6-biphosphatase (PFKFB) expression could result in increased glycolysis, while an increase in pyruvate availability may also result from a lower conversion to acetyl-CoA by negative regulation of pyruvate dehydrogenase complex (PDC) activity by phosphorylation. Sertoli cell cultures obtained from 20-day-old rats were used. Stimulation of the cultures with FSH or bFGF showed that FSH increases Pfkfb1 and Pfkfb3 expression while bFGF increases Pfkfb1 mRNA levels. Additionally, we observed that FSH-stimulated lactate production was inhibited in the presence of a PFKFB3 inhibitor, revealing the p...