Sertoli Cells In Spermatogenesis Research Articles

Proteomic and phosphoproteomic profiles of Sertoli cells in buffalo

Sertoli cells provide nutrients and support for germ cell differentiation and maintain a stable microenvironment for spermatogenesis. Comprehensive identification of Sertoli cellular proteins is important in understanding spermatogenesis. In this study, we performed an integrative analysis of the proteome and phosphoproteome to explore the role of Sertoli cells in spermatogenesis. A total of 2912 and 753 proteins were identified from the proteome and phosphoproteome in Sertoli cells, respectively; 438 proteins were common to the proteome and phosphoproteome. Data are available via ProteomeXchange with identifier PXD024984. In the proteome, ACTG1, ACTB, ACTA2, MYH9 were the most abundant proteins. Gene Ontology (GO) analysis indicated that most of the proteins were involved in the processes of localization, biosynthesis, gene expression, and transport. In addition, some of the proteins related to Sertoli cell functions were also enriched. In the phosphoproteome, most of the proteins were involved in gene expression and the RNA metabolic process; the pathways mainly involved the spliceosome, mitogen-activated protein kinase signaling pathway, focal adhesion, and tight junctions. The pleckstrin homology-like domain is the most highly enriched protein domain in phosphoproteins. Cyclin-dependent kinases and protein kinases C were found to be highly active kinases in the kinase-substrate network analysis. Ten proteins most closely related to network stability were found in the analysis of the network interactions of proteins identified jointly in the phosphoproteome and proteome. Through immunohistochemistry and immunofluorescence verification of vimentin, it was found that there were localization differences between phosphorylated and non-phosphorylated vimentin in testicular tissue. This study is the first in-depth proteomic and phosphoproteomic analysis of buffalo testicular Sertoli cells. The results provide insight into the role of Sertoli cells in spermatogenesis and provide clues for further study of male reproduction.

BRG1 Is Dispensable for Sertoli Cell Development and Functions in Mice.

Sertoli cells are somatic supporting cells in spermatogenic niche and play critical roles in germ cell development, but it is yet to be understood how epigenetic modifiers regulate Sertoli cell development and contribution to spermatogenesis. BRG1 (Brahma related gene 1) is a catalytic subunit of the mammalian SWI/SNF chromatin remodeling complex and participates in transcriptional regulation. The present study aimed to define the functions of BRG1 in mouse Sertoli cells during mouse spermatogenesis. We found that BRG1 protein was localized in the nuclei of both Sertoli cells and germ cells in seminiferous tubules. We further examined the requirement of BRG1 in Sertoli cell development using a Brg1 conditional knockout mouse model and two Amh-Cre mouse strains to specifically delete Brg1 gene from Sertoli cells. We found that the Amh-Cre mice from Jackson Laboratory had inefficient recombinase activities in Sertoli cells, while the other Amh-Cre strain from the European Mouse Mutant Archive achieved complete Brg1 deletion in Sertoli cells. Nevertheless, the conditional knockout of Brg1 from Sertoli cells by neither of Amh-Cre strains led to any detectable abnormalities in the development of either Sertoli cells or germ cells, suggesting that BRG1-SWI/SNF complex is dispensable to the functions of Sertoli cells in spermatogenesis.

The effects of cannabidiol on male reproductive system: A literature review.

Cannabidiol (CBD) is one of the most abundant phytocannabinoids present in the plant Cannabis sativa (marijuana). There have been several studies of CBD in the last few decades, mainly focused on its neuroprotective properties, particularly after the identification of the endocannabinoid system and its participation in the central nervous system. On the other hand, the peripheral effects of CBD, particularly on reproductive physiology, were also evidenced. A narrative review was conducted using the PubMed database to identify studies that analyzed the pharmacological effects of CBD on the male reproductive system of vertebrates and invertebrates. Thirty-two citations (in vivo and in vitro) were identified. Among the vertebrates, the studies were carried out with men, monkeys, rats and mice. Studies with invertebrates are centered exclusively on the sea urchin. The CBD treatment periods include mostly acute and subacute evaluations. Exposure to CBD is associated with a reduction in mammalian testis size, the number of germ and Sertoli cells in spermatogenesis, fertilization rates, and plasma concentrations of hypothalamic, pituitary and gonadal hormones. Moreover, chronic doses of CBD have impaired sexual behavior in mice. From the studies identified in this review, it is possible to conclude that CBD has negative effects on the reproductive system of males. However, knowledge is still limited, and additional research is required to elucidate fully the mechanisms of action, as well as the reversibility of CBD effects on the reproductive system.

50 years of spermatogenesis: Sertoli cells and their interactions with germ cells.

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 cell types from the testicular milieu. Products of Sertoli cells that influence germ cell development and vice versa have been characterized from cultured cells and from the application of transgenic technologies. Germ cell transplantation has shown that the Sertoli cells respond to cues from germ cells with regard to developmental timing and has furthered a focus on spermatogenic stem cells and the stem cell niche. Very basic and universal features of spermatogenesis such as the cycle of the seminiferous epithelium and the spermatogenic wave are initiated by Sertoli cells and maintained by Sertoli-germ cell cooperation.

Androgen Receptor Coactivator ARID4B Is Required for the Function of Sertoli Cells in Spermatogenesis.

Defects in spermatogenesis, a process that produces spermatozoa inside seminiferous tubules of the testis, result in male infertility. Spermatogenic progression is highly dependent on a microenvironment provided by Sertoli cells, the only somatic cells and epithelium of seminiferous tubules. However, genes that regulate such an important activity of Sertoli cells are poorly understood. Here, we found that AT-rich interactive domain 4B (ARID4B), is essential for the function of Sertoli cells to regulate spermatogenesis. Specifically, we generated Sertoli cell-specific Arid4b knockout (Arid4bSCKO) mice, and showed that the Arid4bSCKO male mice were completely infertile with impaired testis development and significantly reduced testis size. Importantly, severe structural defects accompanied by loss of germ cells and Sertoli cell-only phenotype were found in many seminiferous tubules of the Arid4bSCKO testes. In addition, maturation of Sertoli cells was significantly delayed in the Arid4bSCKO mice, associated with delayed onset of spermatogenesis. Spermatogenic progression was also defective, showing an arrest at the round spermatid stage in the Arid4bSCKO testes. Interestingly, we showed that ARID4B functions as a "coactivator" of androgen receptor and is required for optimal transcriptional activation of reproductive homeobox 5, an androgen receptor target gene specifically expressed in Sertoli cells and critical for spermatogenesis. Together, our study identified ARID4B to be a key regulator of Sertoli cell function important for male germ cell development.

The central role of Sertoli cells in spermatogenesis

Sertoli cells are the somatic cells of the testis that are essential for testis formation and spermatogenesis. Sertoli cells facilitate the progression of germ cells to spermatozoa via direct contact and by controlling the environment milieu within the seminiferous tubules. The regulation of spermatogenesis by FSH and testosterone occurs by the action of these hormones on the Sertoli cells. While the action of testosterone is necessary for spermatogenesis, the action of FSH minimally serves to promote spermatogenic output by increasing the number of Sertoli cells.

Interactions between germ cells and Sertoli cells in the testis.

The "nurse cell" function of Sertoli cells in spermatogenesis was originally tacitly assumed on the basis of the anatomical relationships between cells in the testis. In mammals, from very early in prenatal development to the onset of meiosis and to the ultimate production of spermatozoa, the relationship between the germinal cells and the Sertoli cells is important and apparently obligatory. The experimental evidence supports the notion that the primary endocrine regulation of spermatogenesis via FSH and testosterone is manifested through actions on the Sertoli cells. Although diverse strategies are used by Sertoli cells to support germ cell development, one of the most important roles of Sertoli cells is the regulation of the intratubular and intercellular environment adluminal to the tight junctional complexes. The meiotic and post-meiotic germ cells are sequestered by Sertoli-Sertoli junctional complexes in an adluminal compartment that is isolated from the serum or lymph. As a result of this sequestering activity, the secretion products of the Sertoli cells and the meiotic germ cells determine the composition of this local environment that can influence meiosis as well as spermatid and spermatocyte development. Evidence is accumulating that paracrine and autocrine factors from Sertoli and germ cells are important in the functioning of both cell types. While it is important to know what Sertoli cells and germ cells make, it is equally important to know when they make it. Distinct but well-defined groups of germ cells interact with Sertoli cells in a cyclic pattern. These recurring groups of germ cells define the cycle of the seminiferous epithelium during which sperm are produced in an asynchronous fashion.(ABSTRACT TRUNCATED AT 250 WORDS)