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Methods in Molecular Biology (Clifton,... 2018Nuclear magnetic resonance (NMR)-based metabolomics is widely used in the research of metabolic conditions of complex biological systems under various conditions, and...
Nuclear magnetic resonance (NMR)-based metabolomics is widely used in the research of metabolic conditions of complex biological systems under various conditions, and its use has been found in the field of male fertility. Here we describe the implementation of total and targeted NMR-based metabolomics in the research on Sertoli cell metabolism. Main principles and techniques of cell medium, cellular extracts, and intact cells are explained, as well as some classical experiments that can give complementary information on the Sertoli cell metabolism.
Topics: Cells, Cultured; Humans; Magnetic Resonance Spectroscopy; Male; Metabolomics; Sertoli Cells
PubMed: 29453571
DOI: 10.1007/978-1-4939-7698-0_12 -
Progress in Lipid Research Oct 2018Sulfogalactosylglycerolipid (SGG, aka seminolipid) is selectively synthesized in high amounts in mammalian testicular germ cells (TGCs). SGG is an ordered lipid and... (Review)
Review
Sulfogalactosylglycerolipid (SGG, aka seminolipid) is selectively synthesized in high amounts in mammalian testicular germ cells (TGCs). SGG is an ordered lipid and directly involved in cell adhesion. SGG is indispensable for spermatogenesis, a process that greatly depends on interaction between Sertoli cells and TGCs. Spermatogenesis is disrupted in mice null for Cgt and Cst, encoding two enzymes essential for SGG biosynthesis. Sperm surface SGG also plays roles in fertilization. All of these results indicate the significance of SGG in male reproduction. SGG homeostasis is also important in male fertility. Approximately 50% of TGCs become apoptotic and phagocytosed by Sertoli cells. SGG in apoptotic remnants needs to be degraded by Sertoli lysosomal enzymes to the lipid backbone. Failure in this event leads to a lysosomal storage disorder and sub-functionality of Sertoli cells, including their support for TGC development, and consequently subfertility. Significantly, both biosynthesis and degradation pathways of the galactosylsulfate head group of SGG are the same as those of sulfogalactosylceramide (SGC), a structurally related sulfoglycolipid important for brain functions. If subfertility in males with gene mutations in SGG/SGC metabolism pathways manifests prior to neurological disorder, sperm SGG levels might be used as a reporting/predicting index of the neurological status.
Topics: Animals; Fertility; Galactolipids; Homeostasis; Humans; Male; Reproduction; Sertoli Cells; Spermatogenesis; Spermatozoa
PubMed: 30149090
DOI: 10.1016/j.plipres.2018.08.002 -
Reproduction (Cambridge, England) Apr 2015Spermatogenesis is a continuous and productive process supported by the self-renewal and differentiation of spermatogonial stem cells (SSCs), which arise from... (Review)
Review
Spermatogenesis is a continuous and productive process supported by the self-renewal and differentiation of spermatogonial stem cells (SSCs), which arise from undifferentiated precursors known as gonocytes and are strictly controlled in a special 'niche' microenvironment in the seminiferous tubules. Sertoli cells, the only somatic cell type in the tubules, directly interact with SSCs to control their proliferation and differentiation through the secretion of specific factors. Spermatocyte meiosis is another key step of spermatogenesis, which is regulated by Sertoli cells on the luminal side of the blood-testis barrier through paracrine signaling. In this review, we mainly focus on the role of Sertoli cells in the regulation of SSC self-renewal and spermatocyte meiosis, with particular emphasis on paracrine and endocrine-mediated signaling pathways. Sertoli cell growth factors, such as glial cell line-derived neurotrophic factor (GDNF) and fibroblast growth factor 2 (FGF2), as well as Sertoli cell transcription factors, such as ETS variant 5 (ERM; also known as ETV5), nociceptin, neuregulin 1 (NRG1), and androgen receptor (AR), have been identified as the most important upstream factors that regulate SSC self-renewal and spermatocyte meiosis. Other transcription factors and signaling pathways (GDNF-RET-GFRA1 signaling, FGF2-MAP2K1 signaling, CXCL12-CXCR4 signaling, CCL9-CCR1 signaling, FSH-nociceptin/OPRL1, retinoic acid/FSH-NRG/ERBB4, and AR/RB-ARID4A/ARID4B) are also addressed.
Topics: Humans; Male; Meiosis; Sertoli Cells; Signal Transduction; Spermatocytes; Spermatogenesis; Spermatogonia; Stem Cells
PubMed: 25504872
DOI: 10.1530/REP-14-0481 -
Molecular and Cellular Endocrinology May 2021The testis is a temperature-sensitive organ that needs to be maintained 2-7 °C below core body temperature to ensure the production of normal sperm. Failure to... (Review)
Review
The testis is a temperature-sensitive organ that needs to be maintained 2-7 °C below core body temperature to ensure the production of normal sperm. Failure to maintain testicular temperature in mammals impairs spermatogenesis and leads to low sperm counts, poor sperm motility and abnormal sperm morphology in the ejaculate. This review discusses the recent knowledge on the response of testicular somatic cells to heat stress and, specifically, regarding the relevant contributions of heat, germ cell depletion and inflammatory reactions on the functions of Sertoli and Leydig cells. It also outlines mechanisms of testicular thermoregulation, as well as the thermogenic factors that impact testicular function.
Topics: Animals; Heat-Shock Response; Humans; Leydig Cells; Male; Sertoli Cells; Sperm Motility; Spermatogenesis; Spermatozoa
PubMed: 33639219
DOI: 10.1016/j.mce.2021.111216 -
Journal of Applied Toxicology : JAT Aug 2015Pressure towards population aging in the demographic pyramid is not only due to sociological/personal choices but also due to subfertility or infertility. There are... (Review)
Review
Pressure towards population aging in the demographic pyramid is not only due to sociological/personal choices but also due to subfertility or infertility. There are several chemicals and mixtures that impair male fertility. While experimental animal models are crucial to identify compounds that affect male fertility, it is essential to use reliable in vitro models to determine cellular targets and intracellular pathways that mediate chemical toxicity in the male reproductive system. In this review, we focused on the somatic Sertoli cell (SC) that, within the testis, is a major target for hormonal signaling and provides physical and nutritional support to developing germ cells. The different outcomes possible in each type of study: in vivo versus in vitro (either in primary or immortalized cell cultures) are analyzed. Herein, we intend to clarify the unique features that render SCs as excellent candidates for a robust in vitro model to study the deleterious effects of chemicals on male reproductive health. The sensitivity of SCs to toxicants/pharmaceuticals is discussed and, based on the literature reviewed we propose the in vitro study of SC physiology as a model to disclose deleterious effects of substances to male fertility.
Topics: Animals; Blood-Testis Barrier; Humans; Infertility, Male; Male; Metals, Heavy; Models, Biological; Sertoli Cells; Spermatogenesis; Testis
PubMed: 25693974
DOI: 10.1002/jat.3122 -
Molecular Reproduction and Development Sep 2017The sperm cell has a unique, polarized, and segregated surface that is modified extensively by the changing environments in both the male and the female reproductive... (Review)
Review
The sperm cell has a unique, polarized, and segregated surface that is modified extensively by the changing environments in both the male and the female reproductive tracts. The sperm cannot refresh its surface, as protein translation and membrane recycling by intracellular vesicular transport have ceased upon its maturation. So, how is the sperm surface modified in the reproductive tracts and how do these processes affect fertilization? This review traces these modifications as boar sperm travels from their liberation from the Sertoli cell into the lumen of seminiferous tubules of the testis to the site of fertilization in the ampulla of the oviduct in the sow, via an artificial insemination route. The effect of sperm dilution for artificial insemination, as well as more extensive sperm processing for in vitro fertilization, cryopreservation, or sex sorting, are also discussed with respect to how these procedures affect sperm surface organization and fertilization capacity.
Topics: Animals; Cryopreservation; Female; Fertilization in Vitro; Male; Oviducts; Seminiferous Tubules; Sertoli Cells; Spermatozoa; Swine
PubMed: 28452082
DOI: 10.1002/mrd.22821 -
Reproductive Biology and Endocrinology... Jul 2022Follicle-stimulating hormone signaling is essential for the initiation and early stages of spermatogenesis. Follicle-stimulating hormone receptor is exclusively... (Review)
Review
Follicle-stimulating hormone signaling is essential for the initiation and early stages of spermatogenesis. Follicle-stimulating hormone receptor is exclusively expressed in Sertoli cells. As the only type of somatic cell in the seminiferous tubule, Sertoli cells regulate spermatogenesis not only by controlling their own number and function but also through paracrine actions to nourish germ cells surrounded by Sertoli cells. After follicle-stimulating hormone binds to its receptor and activates the follicle-stimulating hormone signaling pathway, follicle-stimulating hormone signaling will establish a normal Sertoli cell number and promote their differentiation. Spermatogonia pool maintenance, spermatogonia differentiation and their entry into meiosis are also positively regulated by follicle-stimulating hormone signaling. In addition, follicle-stimulating hormone signaling regulates germ cell survival and limits their apoptosis. Our review summarizes the aforementioned functions of follicle-stimulating hormone signaling in Sertoli cells. We also describe the clinical potential of follicle-stimulating hormone treatment in male patients with infertility. Furthermore, our review may be helpful for developing better therapies for treating patients with dysfunctional follicle-stimulating hormone signaling in Sertoli cells.
Topics: Animals; Follicle Stimulating Hormone; Humans; Male; Meiosis; Mice; Rats; Sertoli Cells; Signal Transduction; Spermatogenesis; Spermatogonia
PubMed: 35780146
DOI: 10.1186/s12958-022-00971-w -
Theriogenology Sep 2022Elevated glucocorticoid (GC) concentrations associated with captivity-related stress have been linked to impaired testicular function and low sperm quality in felids,...
Elevated glucocorticoid (GC) concentrations associated with captivity-related stress have been linked to impaired testicular function and low sperm quality in felids, but direct physiological evidence is lacking. This study assessed the effects of exogenous GC treatment on felid testicular function using the domestic cat (Felis catus) as a model species. Sixteen intact male cats aged 2.4 ± 0.8 years (mean ± SEM) were divided randomly into treatment (n = 8) and control (n = 8) groups. Treatment cats were given 1 mg kg oral prednisolone daily for 50 days. Blood samples were taken on Days 0 (first prednisolone treatment), 2, 4, 7, 10, 20, 30, 40, 50 (prior to neutering) and 60 of the trial. All cats were orchiectomised on day 50, epididymal sperm assessed, and the testes fixed for histological assessment. Testosterone concentrations did not differ between the two groups. While sperm motility was similar between the treatment and control groups, cats given prednisolone had a higher proportion of morphologically abnormal sperm in both the caput (72.5% vs. 59.6%, P < 0.001) and cauda (56.7% vs. 35.8%, P < 0.001) epididymis. Testicular histomorphometric data and total number of germ cells per seminiferous tubule cross section did not differ between groups, nor did the relative abundance of spermatogonia, spermatocytes, and spermatids. Cats given prednisolone had fewer Sertoli cells per tubule cross-section than those in the control group (17.1 ± 0.9 vs. 19.7 ± 0.8, P = 0.04), which was likely related to higher rates of Sertoli cell apoptosis in treatment versus control cats (0.25 ± 0.02 vs. 0.10 ± 0.02 apoptotic Sertoli cells per tubule, respectively; P < 0.001). Sertoli cell load (number of germ cells per Sertoli cell) was also higher in the treatment group than in the control group (11.5 ± 0.8 vs. 9.4 ± 1.2 germ cells per Sertoli cell, respectively; P < 0.001), and was positively correlated with the percentage of morphologically abnormal sperm in the epididymis (r = 0.78, P < 0.001). Prednisolone treatment resulted in an increase in the proportion of abnormal sperm in the epididymis, which may be explained by an increased nurturing demand on a reduced Sertoli cell population. These findings provide novel evidence to support the hypothesis that elevated GC concentrations, such as those resulting from captivity-related stress, have the potential to impair testicular function and sperm quality in felids.
Topics: Animals; Cats; Epididymis; Glucocorticoids; Male; Prednisolone; Semen; Sertoli Cells; Sperm Motility; Spermatids; Spermatogenesis; Spermatozoa; Testis
PubMed: 35714522
DOI: 10.1016/j.theriogenology.2022.05.026 -
Genes Nov 2019Testis cords are the embryonic precursors of the seminiferous tubules. Development of testis cords is a key event during embryonic testicular morphogenesis and is...
Testis cords are the embryonic precursors of the seminiferous tubules. Development of testis cords is a key event during embryonic testicular morphogenesis and is regulated by multiple signaling molecules produced by Sertoli cells. However, the exact nature and the cascade of molecular events underlying testis cord development remain to be uncovered. In the current study, we explored the role of DNA damage binding protein 1 (DDB1) in Sertoli cells during mouse testis cord development. The genetic ablation of specifically in Sertoli cells resulted in the compromised Sertoli cell proliferation and disruption of testis cord remodeling in neonatal mice. This testicular dysgenesis persisted through adulthood, resulting in smaller testis and low sperm production. Mechanistically, we observed that the DDB1 degradation can stabilize SET domain-containing lysine methyltransferase 8 (SET8), which subsequently decreases the phosphorylation of SMAD2, an essential intracellular component of transforming growth factor beta (TGFβ) signaling. Taken together, our results suggest an essential role of in Sertoli cell proliferation and normal remodeling of testis cords via TGFβ pathway. To our knowledge, this is the first upstream regulators of TGFβ pathway in Sertoli cells, and therefore it furthers our understanding of testis cord development.
Topics: Animals; Animals, Newborn; Cell Proliferation; DNA-Binding Proteins; Gene Deletion; Male; Mice; Sertoli Cells; Signal Transduction; Spermatic Cord; Transforming Growth Factor beta
PubMed: 31779270
DOI: 10.3390/genes10120974 -
Reproduction in Domestic Animals =... Mar 2021Sertoli cells are the only somatic cells in the seminiferous epithelium which directly contact with germ cells. Sertoli cells exhibit polarized alignment at the basal...
Sertoli cells are the only somatic cells in the seminiferous epithelium which directly contact with germ cells. Sertoli cells exhibit polarized alignment at the basal membrane of seminiferous tubules to maintain the microenvironment for growth and development of germ cells, and therefore play a crucial role in spermatogenesis. Androgens exert their action through androgen receptor (AR) and AR signalling in the testis is essential for maintenance of spermatogonial numbers, blood-testis barrier integrity, completion of meiosis, adhesion of spermatids and spermiation. In the present study, we demonstrated that AR gene could promote the proliferation of immature porcine Sertoli cells (ST cells) and the cell cycle procession, and accelerate the transition from G1 phase into S phase in ST cells. Meanwhile, miR-124a could affect the proliferation and cell cycle procession of ST cells by targeting 3'-UTR of AR gene. Furthermore, AR bound to the RNF4 via AR DNA-binding domain (DBD) and we verified that RNF4 was necessary for AR to regulate the growth of ST cells. Above all, this study suggests that AR regulates ST cell growth via binding to RNF4 and miR-124a, which may help us to further understand the function of AR in spermatogenesis.
Topics: 3' Untranslated Regions; Animals; Cell Cycle; Cell Line; Cell Proliferation; DNA-Binding Proteins; Gene Expression; Male; MicroRNAs; Nuclear Proteins; Protein Domains; Receptors, Androgen; Sertoli Cells; Swine; Transcription Factors
PubMed: 33305371
DOI: 10.1111/rda.13877