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

scholarly journals Health concerns regarding the effect of the COVID-19 pandemic on male fertility

2021 ◽  
Author(s):  
Hamidreza Mosleh ◽  
Fatemeh Moradi ◽  
Mehdi Mehdizadeh ◽  
Marziyeh Ajdary ◽  
Alaa Moeinzadeh ◽  
...  
Keyword(s):  
Male Infertility ◽  
Sertoli Cells ◽  
Leydig Cells ◽  
Renin Angiotensin System ◽  
High Expression ◽  
Angiotensin System ◽  
Angiotensin Converting Enzyme 2 ◽  
Testicular Cells ◽  
Novel Coronavirus ◽  
High Expression Level

Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) is a novel coronavirus found in China in 2019. The disease caused by SARS-CoV-2, coronavirus disease 2019 (COVID-19), has been found to be closely related to the cells that secrete angiotensin-converting enzyme 2 (ACE2). ACE2 is involved in the renin-angiotensin system and is widely secreted in several tissues, including the testis, which has raised concerns because organs with high expression of the ACE2 receptor are susceptible to infection. Analyses have shown that in testicular cells, such as spermatogonia, seminiferous duct cells, Sertoli cells, and Leydig cells, there is a high expression level of ACE2. Therefore, SARS-CoV-2 may damage male reproductive tissues and cause infertility. Since male infertility is an important problem, scientists are evaluating whether COVID-19 may influence male infertility through the ACE2 receptor.

scholarly journals Functions of TAM RTKs in regulating spermatogenesis and male fertility in mice

Reproduction ◽  
2009 ◽  
Vol 138 (4) ◽  
pp. 655-666 ◽  
Author(s):  
Yongmei Chen ◽  
Huizhen Wang ◽  
Nan Qi ◽  
Hui Wu ◽  
Weipeng Xiong ◽  
...  
Keyword(s):  
Germ Cells ◽  
Sertoli Cells ◽  
Tyrosine Kinases ◽  
Male Fertility ◽  
Leydig Cells ◽  
Seminiferous Tubules ◽  
Wild Type ◽  
Male Sterile ◽  
Triple Mutant ◽  
Insight Into

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.

Review of Sertoli cell dysfunction caused by COVID-19 that could affect male fertility

Zygote ◽  
2021 ◽  
pp. 1-8
Author(s):  
Amirreza Niazi Tabar ◽  
Kiana Sojoudi ◽  
Hannaneh Henduei ◽  
Hossein Azizi
Keyword(s):  
Severe Acute Respiratory Syndrome ◽  
Angiotensin Converting Enzyme ◽  
Germ Cells ◽  
Sertoli Cells ◽  
Reproductive System ◽  
Male Fertility ◽  
Differentiation Process ◽  
Converting Enzyme ◽  
Cell Dysfunction ◽  
Testicular Cells

Abstract Spermatogenesis is a complex and elaborate differentiation process and is vital for male fertility. Sertoli cells play a major role in fertility and induce spermatogenesis by protecting, nourishing, and supporting germ cells. It has been speculated that severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) could directly affect the male reproductive system, and therefore heredity and fertility. The similarity of SARS-CoV-2 to SARS-CoV could confirm this hypothesis because both viruses use angiotensin-converting enzyme (ACE2) as the receptor to enter human cells. ACE2 is expressed by Sertoli cells and other testicular cells, therefore COVID-19 has the potential to impair fertility by destroying Sertoli cells. This hypothesis should be evaluated and confirmed by monitoring fertility in patients with COVID-19.

scholarly journals Kindlin-2 in Sertoli cells is essential for testis development and male fertility in mice

2021 ◽  
Vol 12 (6) ◽  
Author(s):  
Xiaochun Chi ◽  
Weiwei Luo ◽  
Jiagui Song ◽  
Bing Li ◽  
Tiantian Su ◽  
...  
Keyword(s):  
Sertoli Cells ◽  
Male Fertility ◽  
Nuclear Translocation ◽  
Hippo Pathway ◽  
Reproductive Organs ◽  
Male Reproduction ◽  
Barrier Structure ◽  
Male Mice ◽  
Sperm Development

AbstractKindlin-2 is known to play important roles in the development of mesoderm-derived tissues including myocardium, smooth muscle, cartilage and blood vessels. However, nothing is known for the role of Kindlin-2 in mesoderm-derived reproductive organs. Here, we report that loss of Kindlin-2 in Sertoli cells caused severe testis hypoplasia, abnormal germ cell development and complete infertility in male mice. Functionally, loss of Kindlin-2 inhibits proliferation, increases apoptosis, impairs phagocytosis in Sertoli cells and destroyed the integration of blood-testis barrier structure in testes. Mechanistically, Kindlin-2 interacts with LATS1 and YAP, the key components of Hippo pathway. Kindlin-2 impedes LATS1 interaction with YAP, and depletion of Kindlin-2 enhances LATS1 interaction with YAP, increases YAP phosphorylation and decreases its nuclear translocation. For clinical relevance, lower Kindlin-2 expression and decreased nucleus localization of YAP was found in SCOS patients. Collectively, we demonstrated that Kindlin-2 in Sertoli cells is essential for sperm development and male reproduction.

scholarly journals Minireview: Transcriptional Regulation of Gonadal Development and Differentiation

Endocrinology ◽  
2005 ◽  
Vol 146 (3) ◽  
pp. 1035-1042 ◽  
Author(s):  
Susan Y. Park ◽  
J. Larry Jameson
Keyword(s):  
Germ Cells ◽  
Sertoli Cells ◽  
Leydig Cells ◽  
Cell Types ◽  
Gonadal Development ◽  
Targeted Mutagenesis ◽  
Seminiferous Tubules ◽  
Molecular Pathways ◽  
Theca Cells ◽  
Main Cell

The embryonic gonad is undifferentiated in males and females until a critical stage when the sex chromosomes dictate its development as a testis or ovary. This binary developmental process provides a unique opportunity to delineate the molecular pathways that lead to distinctly different tissues. The testis comprises three main cell types: Sertoli cells, Leydig cells, and germ cells. The Sertoli cells and germ cells reside in seminiferous tubules where spermatogenesis occurs. The Leydig cells populate the interstitial compartment and produce testosterone. The ovary also comprises three main cell types: granulosa cells, theca cells, and oocytes. The oocytes are surrounded by granulosa and theca cells in follicles that grow and differentiate during characteristic reproductive cycles. In this review, we summarize the molecular pathways that regulate the distinct differentiation of these cell types in the developing testis and ovary. In particular, we focus on the transcription factors that initiate these cascades. Although most of the early insights into the sex determination pathway were based on human mutations, targeted mutagenesis in mouse models has revealed key roles for genes not anticipated to regulate gonadal development. Defining these molecular pathways provides the foundation for understanding this critical developmental event and provides new insight into the causes of gonadal dysgenesis.

Expression of nerve growth factor and neurotrophin receptors in testicular cells suggest novel roles for neurotrophins outside the nervous system

1996 ◽  
Vol 8 (7) ◽  
pp. 1075 ◽  
Author(s):  
K Seidl ◽  
A Buchberger ◽  
C Erck
Keyword(s):  
Nerve Growth Factor ◽  
Growth Factor ◽  
Germ Cells ◽  
Sertoli Cells ◽  
Leydig Cells ◽  
Expression Patterns ◽  
Myoid Cells ◽  
Nerve Growth ◽  
High Affinity ◽  
Ngf Receptor

The present study was designed to clarify the non-neurotrophic role for neurotrophins in mouse testis. By means of SI nuclease protection assay we could demonstrate that the gene coding for the low-affinity nerve growth factor (NGF) receptor p75NGFR is transiently expressed during germ cell development. Gene expression for p75NGFR was detected in late-meiotic spermatocytes and early spermatids and was found to be co-expressed with trkB and trkC, two tyrosine kinase receptors, commonly regarded as the high-affinity receptors for brain-derived neurotrophic factor and neurotrophin-3. Gene transcripts for the high-affinity NGF receptor trkA were found exclusively in non-germ cells. Isolated Leydig cells, peritubular myoid cells and Sertoli cells, but not germ cells, could be identified as potential testicular NGF sources. Non-germ cells respond after incubation for several days with a sharp induction in NGF synthesis, which is accompanied by a loss of phenotypic expression patterns. The fact that p75NGFR mRNA expression was induced in cultured Sertoli cells and peritubular myoid cells suggests an autocrine mode of NGF action in these cells. Induction of NGF synthesis in cultured Leydig cells could be prevented by the glucocorticoid dexamethasone. Results indicate different roles for the individual neurotrophins in distinct testicular compartments and suggest that these neurotrophins might support testicular functions by signalling between individual cell types in an autocrine and paracrine manner.

scholarly journals Bovine fetal testicular development in the Nellore breed

2017 ◽  
Vol 38 (4Supl1) ◽  
pp. 2551
Author(s):  
Juliana Stephany de Souza ◽  
Maria Carolina Villani Miguel ◽  
Marcos Antônio Maioli ◽  
Arthur Nelson Trali Neto ◽  
David Giraldo Arana ◽  
...  
Keyword(s):  
Germ Cells ◽  
Sertoli Cells ◽  
Leydig Cells ◽  
Principal Component ◽  
Gonadal Development ◽  
Cell Number ◽  
Testicular Development ◽  
Testosterone Concentration ◽  
Testicular Weight ◽  
Bovine Fetuses

The study of gonadal development improves the understanding of factors that can influence the reproductive development process. This study aims to characterize bovine fetal testicular development and the testosterone level in the Nellore breed. For the study, 162 bovine fetuses aged between 3 and 8 months were collected from Nellore cows at a local abattoir. The fetal age was estimated by DP=8.4+0.087L+5.46?L, where DP is the estimated pregnancy day and L represents fetal length. The fetal gonadal weight (g), width (cm), and thickness (cm) were measured. Thereafter, the gonads were submitted to classic histology processes in 3-µm-thick slices cut at 210 µm intervals. The Sertoli cells, Leydig cells, and germ cells were counted. Blood samples were collected from umbilical cords for testosterone levels. The data were analyzed using the Spearman correlation test followed by Principal Component Analysis and one-way ANOVA to compare the averages between months. The testicular weight and volume were found to have a positive correlation with the numbers of Sertoli cells (r = 0.84; p < 0.0001 and r = 0.92; p < 0.0001, respectively), Leydig cells (r = 0.80; p < 0.0001 and r = 0.90; p < 0.0001, respectively), and germ cells (r = 0.84; p < 0.0001 and r = 0.93; p < 0.0001, respectively) and to be negatively correlated with testosterone plasmatic concentration (r = -0.31; p = 0.0001 and r = -0.22; p = 0.006, respectively) during pregnancy. After the fifth month, the numbers of Sertoli cells, Leydig cells and germ cells differed (p < 0.0001) from the following gestational months. The highest testosterone concentration (p = 0.007) was observed in the fifth month of gestation and was followed by a concentration decrease in the seventh and eighth months. The increase in cell quantity was responsible for the increase in testicular weight and volume during fetal development. On the other hand, the testosterone concentration followed the increase in testicular weight and volume until the 7th month of gestation and regressed during the 8th and 9th months, in addition to the increase in cell number.

scholarly journals Expression Analysis ofGnrh1andGnrhr1in Spermatogenic Cells of Rat

2015 ◽  
Vol 2015 ◽  
pp. 1-8 ◽  
Author(s):  
Vincenza Ciaramella ◽  
Rosanna Chianese ◽  
Paolo Pariante ◽  
Silvia Fasano ◽  
Riccardo Pierantoni ◽  
...  
Keyword(s):  
Germ Cells ◽  
Sertoli Cells ◽  
Leydig Cells ◽  
Spermatogenic Cells ◽  
Myoid Cells ◽  
Quantitative Real Time Pcr ◽  
The Past ◽  
Expression Rate ◽  
Sperm Functions

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.

scholarly journals Androgen Receptor Roles in Spermatogenesis and Fertility: Lessons from Testicular Cell-Specific Androgen Receptor Knockout Mice

2009 ◽  
Vol 30 (2) ◽  
pp. 119-132 ◽  
Author(s):  
Ruey-Sheng Wang ◽  
Shuyuan Yeh ◽  
Chii-Ruey Tzeng ◽  
Chawnshang Chang
Keyword(s):  
Androgen Receptor ◽  
Germ Cells ◽  
Sertoli Cells ◽  
Knockout Mice ◽  
Leydig Cells ◽  
Cell Types ◽  
Myoid Cells ◽  
Testicular Cell ◽  
Male Phenotype ◽  
The Impact

Abstract Androgens are critical steroid hormones that determine the expression of the male phenotype, including the outward development of secondary sex characteristics as well as the initiation and maintenance of spermatogenesis. Their actions are mediated by the androgen receptor (AR), a member of the nuclear receptor superfamily. AR functions as a ligand-dependent transcription factor, regulating expression of an array of androgen-responsive genes. Androgen and the AR play important roles in male spermatogenesis and fertility. The recent generation and characterization of male total and conditional AR knockout mice from different laboratories demonstrated the necessity of AR signaling for both external and internal male phenotype development. As expected, the male total AR knockout mice exhibited female-typical external appearance (including a vagina with a blind end and a clitoris-like phallus), the testis was located abdominally, and germ cell development was severely disrupted, which was similar to a human complete androgen insensitivity syndrome or testicular feminization mouse. However, the process of spermatogenesis is highly dependent on autocrine and paracrine communication among testicular cell types, and the disruption of AR throughout an experimental animal cannot answer the question about how AR in each type of testicular cell can play roles in the process of spermatogenesis. In this review, we provide new insights by comparing the results of cell-specific AR knockout in germ cells, peritubular myoid cells, Leydig cells, and Sertoli cells mouse models that were generated by different laboratories to see the consequent defects in spermatogenesis due to AR loss in different testicular cell types in spermatogenesis. Briefly, this review summarizes these results as follows: 1) the impact of lacking AR in Sertoli cells mainly affects Sertoli cell functions to support and nurture germ cells, leading to spermatogenesis arrest at the diplotene primary spermatocyte stage prior to the accomplishment of first meiotic division; 2) the impact of lacking AR in Leydig cells mainly affects steroidogenic functions leading to arrest of spermatogenesis at the round spermatid stage; 3) the impact of lacking AR in the smooth muscle cells and peritubular myoid cells in mice results in similar fertility despite decreased sperm output as compared to wild-type controls; and 4) the deletion of AR gene in mouse germ cells does not affect spermatogenesis and male fertility. This review tries to clarify the useful information regarding how androgen/AR functions in individual cells of the testis. The future studies of detailed molecular mechanisms in these in vivo animals with cell-specific AR knockout could possibly lead to useful insights for improvements in the treatment of male infertility, hypogonadism, and testicular dysgenesis syndrome, and in attempts to create safe as well as effective male contraceptive methods.

scholarly journals Peroxisomal Multifunctional Protein 2 Is Essential for Lipid Homeostasis in Sertoli Cells and Male Fertility in Mice

Endocrinology ◽  
2006 ◽  
Vol 147 (5) ◽  
pp. 2228-2236 ◽  
Author(s):  
Steven Huyghe ◽  
Henning Schmalbruch ◽  
Karel De Gendt ◽  
Guido Verhoeven ◽  
Florian Guillou ◽  
...  
Keyword(s):  
Germ Cells ◽  
Sertoli Cells ◽  
Male Fertility ◽  
Neutral Lipids ◽  
Docosapentaenoic Acid ◽  
Testicular Atrophy ◽  
Lipid Homeostasis ◽  
Peroxisome Proliferator ◽  
Peroxisome Proliferator Activated Receptor ◽  
Multifunctional Protein

Inactivation of peroxisomal β-oxidation in mice, by knocking out multifunctional protein-2 (MFP-2; also called d-bifunctional enzyme), causes male infertility. In the testis, extensive accumulations of neutral lipids were observed in Sertoli cells, beginning in prepubertal mice and evolving in complete testicular atrophy by the age of 4 months. Spermatogenesis was already severely affected at the age of 5 wk, and pre- and postmeiotic germ cells gradually disappeared from the tubuli seminiferi. Based on cytochemical stainings and biochemical analyses, the lipid droplets consisted of cholesteryl esters and neutral glycerolipids. Furthermore, peroxisomal β-oxidation substrates, such as very-long-chain fatty acids and pristanic acid, accumulated in the testis, whereas the concentration of docosapentaenoic acid, a polyunsaturated fatty acid and peroxisomal β-oxidation product, was reduced. The testicular defects were also present in double MFP-2/peroxisome proliferator-activated receptor-α knockout mice, ruling out the possibility that they were mediated through the activation of this nuclear receptor. Immunoreactivity for peroxisomal proteins, including MFP-2, was detected in Sertoli cells as well as in germ cells and Leydig cells. The pivotal role of peroxisomal metabolism in Sertoli cells was also demonstrated by generating mice with a Sertoli cell-selective elimination of peroxisomes through cell type-specific inactivation of the peroxin 5 gene. These mice also developed lipid inclusions and were infertile, and their testes fully degenerated by the age of 4 months. In conclusion, the present data demonstrate that peroxisomal β-oxidation is essential for lipid homeostasis in the testis and for male fertility.

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