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Frontiers in Endocrinology 2022The Sertoli cells of the testes play an essential role during gonadal development, in addition to supporting subsequent germ cell survival and spermatogenesis.... (Review)
Review
The Sertoli cells of the testes play an essential role during gonadal development, in addition to supporting subsequent germ cell survival and spermatogenesis. Anti-Müllerian hormone (AMH) is a member of the TGF-β superfamily, which is secreted by immature Sertoli cells from the 8 week of fetal gestation. lnhibin B is a glycoprotein, which is produced by the Sertoli cells from early in fetal development. In people with a Difference or Disorder of Sex Development (DSD), these hormones may be useful to determine the presence of testicular tissue and potential for spermatogenesis. However, fetal Sertoli cell development and function is often dysregulated in DSD conditions and altered production of Sertoli cell hormones may be detected throughout the life course in these individuals. As such this review will consider the role of AMH and inhibin B in individuals with DSD.
Topics: Anti-Mullerian Hormone; Disorders of Sex Development; Humans; Inhibin-beta Subunits; Inhibins; Male; Sertoli Cells; Sex Differentiation; Spermatogenesis; Testis
PubMed: 35909548
DOI: 10.3389/fendo.2022.919670 -
Frontiers in Endocrinology 2023Spermatogenesis is a multi-step process of male germ cell (Gc) division and differentiation which occurs in the seminiferous tubules of the testes under the regulation... (Review)
Review
Spermatogenesis is a multi-step process of male germ cell (Gc) division and differentiation which occurs in the seminiferous tubules of the testes under the regulation of gonadotropins - Follicle Stimulating Hormone (FSH) and Luteinising hormone (LH). It is a highly coordinated event regulated by the surrounding somatic testicular cells such as the Sertoli cells (Sc), Leydig cells (Lc), and Peritubular myoid cells (PTc). FSH targets Sc and supports the expansion and differentiation of pre-meiotic Gc, whereas, LH operates Lc to produce Testosterone (T), the testicular androgen. T acts on all somatic cells e.g.- Lc, PTc and Sc, and promotes the blood-testis barrier (BTB) formation, completion of Gc meiosis, and spermiation. Studies with hypophysectomised or chemically ablated animal models and hypogonadal (hpg) mice supplemented with gonadotropins to genetically manipulated mouse models have revealed the selective and synergistic role(s) of hormones in regulating male fertility. We here have briefly summarized the present concept of hormonal control of spermatogenesis in rodents and primates. We also have highlighted some of the key critical questions yet to be answered in the field of male reproductive health which might have potential implications for infertility and contraceptive research in the future.
Topics: Male; Mice; Animals; Spermatogenesis; Testis; Sertoli Cells; Gonadotropins; Follicle Stimulating Hormone; Luteinizing Hormone; Mammals
PubMed: 37124741
DOI: 10.3389/fendo.2023.1110572 -
Molecular and Cellular Endocrinology Oct 2023Antioxidant actions of melatonin and its impact on testicular function and fertility have already been described. Considering that Sertoli cells contribute to provide...
Antioxidant actions of melatonin and its impact on testicular function and fertility have already been described. Considering that Sertoli cells contribute to provide structural support and nutrition to germ cells, we evaluated the effect of melatonin on oxidative state and lactate metabolism in the immature murine TM4 cell line and in immature hamster Sertoli cells. A prooxidant stimulus applied to rodent Sertoli cells expressing MT1/MT2 receptors, increased lipid peroxidation whereas decreased antioxidant enzymes (superoxide dismutase 1, catalase, peroxiredoxin 1) expression and catalase activity. These changes were prevented by melatonin. Furthermore, melatonin stimulated lactate dehydrogenase (LDH) expression/activity via melatonin receptors, and increased intracellular lactate production in rodent Sertoli cells. Interestingly, oral melatonin supplementation in infertile men positively regulated LDHA testicular mRNA expression. Overall, our work provides insights into the potential benefits of melatonin on Sertoli cells contributing to testicular development and the future establishment of a sustainable spermatogenesis.
Topics: Male; Cricetinae; Mice; Animals; Sertoli Cells; Melatonin; Catalase; Antioxidants; Rodentia; Oxidative Stress; Lactates
PubMed: 37516434
DOI: 10.1016/j.mce.2023.112034 -
Frontiers in Endocrinology 2022Since their initial description by Enrico Sertoli in 1865, Sertoli cells have continued to enchant testis biologists. Testis size and germ cell carrying capacity are... (Review)
Review
Since their initial description by Enrico Sertoli in 1865, Sertoli cells have continued to enchant testis biologists. Testis size and germ cell carrying capacity are intimately tied to Sertoli cell number and function. One critical Sertoli cell function is signaling from Sertoli cells to germ cells as part of regulation of the spermatogenic cycle. Sertoli cell signals can be endocrine or paracrine in nature. Here we review recent advances in understanding the interplay of Sertoli cell endocrine and paracrine signals that regulate germ cell state. Although these findings have long-term implications for treating male infertility, recent breakthroughs in Sertoli cell transplantation have more immediate implications. We summarize the surge of advances in Sertoli cell ablation and transplantation, both of which are wedded to a growing understanding of the unique Sertoli cell niche in the transitional zone of the testis.
Topics: Humans; Infertility, Male; Male; Sertoli Cells; Signal Transduction; Spermatogenesis; Testis
PubMed: 35600584
DOI: 10.3389/fendo.2022.897196 -
Andrology May 2021The direct correlation between Sertoli cell number and sperm production capacity highlights the importance of deciphering external factors that modify Sertoli cell...
BACKGROUND
The direct correlation between Sertoli cell number and sperm production capacity highlights the importance of deciphering external factors that modify Sertoli cell proliferation. A growing body of evidence in vitro suggests that metformin, the main pharmacological agent for type 2 diabetes treatment in children, exerts anti-proliferative effects on Sertoli cells.
OBJECTIVE
The aims of this study were to investigate the effect of metformin administration during postnatal period on Sertoli cell proliferation and on cell cycle regulators expression and to analyze the impact of this treatment on the sperm production capacity in adulthood.
MATERIALS AND METHODS
Sprague Dawley rat pups were randomly divided into two groups: MET (receiving daily 200 mg/kg metformin, from Pnd3 to Pnd7 inclusive) and control (receiving vehicle). BrdU incorporation was measured to assess proliferation. Gene expression analyses were performed in Sertoli cells isolated from animals of both groups. Daily sperm production and sperm parameters were measured in adult male rats (Pnd90) that received neonatal treatment.
RESULTS
MET group exhibited a significant decrease in BrdU incorporation in Sertoli cells. Concordantly, MET group showed a reduction in cyclin D1 and E2 expression and an increase in p21 expression in Sertoli cells. In addition, metformin-treated animals displayed lower values of daily sperm production on Pnd90.
DISCUSSION AND CONCLUSION
These results suggest that metformin treatment may lead to a decrease in Sertoli cell proliferation, a concomitant altered expression of cell cycle regulators and ultimately, a reduction in daily sperm production in adult animals.
Topics: Animals; Animals, Newborn; Cell Proliferation; Drug Evaluation, Preclinical; Female; Hypoglycemic Agents; Male; Metformin; Pregnancy; Rats, Sprague-Dawley; Sertoli Cells; Spermatogenesis; Rats
PubMed: 33305512
DOI: 10.1111/andr.12957 -
Cellular and Molecular Life Sciences :... Aug 2022Sertoli cells contribute to the formation of the blood-testis barrier (BTB), which is necessary for normal spermatogenesis. Recently, microRNAs (miRNAs) have emerged as...
Sertoli cells contribute to the formation of the blood-testis barrier (BTB), which is necessary for normal spermatogenesis. Recently, microRNAs (miRNAs) have emerged as posttranscriptional regulatory elements in BTB function during spermatogenesis. Our previous study has shown that miR-181c or miR-181d (miR-181c/d) is highly expressed in testes from boars at 60 days old compared with at 180 days old. Herein, we found that overexpression of miR-181c/d via miR-181c/d mimics in murine Sertoli cells (SCs) or through injecting miR-181c/d-overexpressing lentivirus in murine testes perturbs BTB function by altering BTB-associated protein distribution at the Sertoli cell-cell interface and F-actin organization, but this in vivo perturbation disappears approximately 6 weeks after the final treatment. We also found that miR-181c/d represses Sertoli cell proliferation and promotes its apoptosis. Moreover, miR-181c/d regulates Sertoli cell survival and barrier function by targeting platelet-activating factor acetylhydrolase 1b regulatory subunit 1 (Pafah1b1) gene. Furthermore, miR-181c/d suppresses PAFAH1B1 expression, reduces the complex of PAFAH1B1 with IQ motif-containing GTPase activating protein 1, and inhibits CDC42/PAK1/LIMK1/Cofilin pathway which is required for F-actin stabilization. In total, our results reveal the regulatory axis of miR-181c/d-Pafah1b1 in cell survival and barrier function of Sertoli cells and provide additional insights into miRNA functions in mammalian spermatogenesis.
Topics: 1-Alkyl-2-acetylglycerophosphocholine Esterase; Actins; Animals; Cell Survival; Male; Mammals; Mice; MicroRNAs; Microtubule-Associated Proteins; Rats; Rats, Sprague-Dawley; Sertoli Cells; Spermatogenesis; Swine; Tight Junctions
PubMed: 36008729
DOI: 10.1007/s00018-022-04521-w -
Frontiers in Endocrinology 2023Sertoli cells play essential roles in male reproduction, from supporting fetal testis development to nurturing male germ cells from fetal life to adulthood.... (Review)
Review
Sertoli cells play essential roles in male reproduction, from supporting fetal testis development to nurturing male germ cells from fetal life to adulthood. Dysregulating Sertoli cell functions can have lifelong adverse effects by jeopardizing early processes such as testis organogenesis, and long-lasting processes such as spermatogenesis. Exposure to endocrine disrupting chemicals (EDCs) is recognized as contributing to the rising incidence of male reproductive disorders and decreasing sperm counts and quality in humans. Some drugs also act as endocrine disruptors by exerting off-target effects on endocrine tissues. However, the mechanisms of toxicity of these compounds on male reproduction at doses compatible with human exposure are still not fully resolved, especially in the case of mixtures, which remain understudied. This review presents first an overview of the mechanisms regulating Sertoli cell development, maintenance, and functions, and then surveys what is known on the impact of EDCs and drugs on immature Sertoli cells, including individual compounds and mixtures, and pinpointing at knowledge gaps. Performing more studies on the impact of mixtures of EDCs and drugs at all ages is crucial to fully understand the adverse outcomes these chemicals may induce on the reproductive system.
Topics: Male; Humans; Sertoli Cells; Endocrine Disruptors; Semen; Testis; Pharmaceutical Preparations
PubMed: 36793282
DOI: 10.3389/fendo.2023.1095894 -
Biology of Reproduction Nov 2022TAR DNA binding protein of 43 kD (TDP-43) is an evolutionarily conserved, ubiquitously expressed transcription factor and RNA-binding protein with major human health...
TAR DNA binding protein of 43 kD (TDP-43) is an evolutionarily conserved, ubiquitously expressed transcription factor and RNA-binding protein with major human health relevance. TDP-43 is present in Sertoli and germ cells of the testis and is aberrantly expressed in the sperm of infertile men. Sertoli cells play a key role in spermatogenesis by offering physical and nutritional support to male germ cells. The current study investigated the requirement of TDP-43 in Sertoli cells. Conditional knockout (cKO) of TDP-43 in mouse Sertoli cells caused failure of spermatogenesis and male subfertility. The cKO mice showed decreased testis weight, and low sperm count. Testis showed loss of germ cell layers, presence of vacuoles, and sloughing of round spermatids, suggesting loss of contact with Sertoli cells. Using a biotin tracer, we found that the blood-testis barrier (BTB) was disrupted as early as postnatal day 24 and worsened in adult cKO mice. We noted aberrant expression of the junction proteins connexin-43 (gap junction) and N-cadherin (ectoplasmic specialization). Oil Red O staining showed a decrease in lipid droplets (phagocytic function) in tubule cross-sections, Sertoli cells cytoplasm, and in the lumen of seminiferous tubules of cKO mice. Finally, qRT-PCR showed upregulation of genes involved in the formation and/or maintenance of Sertoli cell junctions as well as in the phagocytic pathway. Sertoli cells require TDP-43 for germ cell attachment, formation and maintenance of BTB, and phagocytic function, thus indicating an essential role for TDP-43 in the maintenance of spermatogenesis.
Topics: Animals; Male; Mice; Blood-Testis Barrier; DNA-Binding Proteins; Semen; Sertoli Cells; Spermatids; Spermatogenesis; Testis
PubMed: 35986894
DOI: 10.1093/biolre/ioac165 -
International Journal of Molecular... Dec 2022Autophagy, an evolutionarily conserved cell reprogramming mechanism, exists in all eukaryotic organisms. It is a fundamental and vital degradation/recycling pathway that... (Review)
Review
Autophagy, an evolutionarily conserved cell reprogramming mechanism, exists in all eukaryotic organisms. It is a fundamental and vital degradation/recycling pathway that removes undesirable components, such as cytoplasmic organelles, misfolded proteins, viruses, and intracellular bacteria, to provide energy and essential materials for organisms. The success of male reproduction depends on healthy testes, which are mainly composed of seminiferous tubules and mesenchyme. Seminiferous tubules are composed of Sertoli cells (SCs) and various germ cells, and the main functional part of mesenchyme are Leydig cells (LCs). In recent years, a large amount of evidence has confirmed that autophagy is active in many cellular events associated with the testes. Autophagy is not only important for testicular spermatogenesis, but is also an essential regulatory mechanism for the ectoplasmic specialization (ES) integrity of SCs, as well as for the normal function of the blood-testes barrier (BTB). At the same time, it is active in LCs and is crucial for steroid production and for maintaining testosterone levels. In this review, we expanded upon the narration regarding the composition of the testes; summarized the regulation and molecular mechanism of autophagy in SCs, germ cells, and LCs; and concluded the roles of autophagy in the process of spermatogenesis and testicular endocrinology. Through integrating the latest summaries and advances, we discuss how the role of autophagy is a double-edged sword in the testes and may provide insight for future studies and explorations on autophagy in male reproduction.
Topics: Male; Humans; Blood-Testis Barrier; Sertoli Cells; Spermatogenesis; Testis; Autophagy
PubMed: 36499597
DOI: 10.3390/ijms232315273 -
Environmental Toxicology Jan 2022Benzophenone-3 (BP-3), one of the most commonly utilized ultraviolet filters in personal care products, has aroused public concern in recent years for its high chances...
Benzophenone-3 (BP-3), one of the most commonly utilized ultraviolet filters in personal care products, has aroused public concern in recent years for its high chances of human exposure. Previous studies have found that BP-3 can impair testes development and spermatogenesis, but the targets of BP-3 are still unknown. In this study, primary Sertoli cells from 20-day-old mice were treated in vitro with 0-100 μM BP-3 for 24 h to identify its toxicity on Sertoli cells and Sertoli cell barrier. Results demonstrated that BP-3 could induce a notable change in cell morphology and impair Sertoli cell viability. The analysis of transepithelial electrical resistance showed that the integrity of the Sertoli cell barrier was destroyed by BP-3 (100 μM). Some structural proteins of the barrier including ZO-1, Occludin, and Connexin43 were lower expressed and the localization of basal ectoplasmic specializations protein β-catenin was altered because of BP-3 treatment. Further exploration suggested that BP-3 led to Sertoli cell F-actin disorganization by affecting the expression of Rictor, a key component of the mTORC2 complex. Moreover, although increased DNA damage marker γH2A.X was observed in the treatment group, the cell apoptosis rate was changeless which was further confirmed by increased BAX and stable Bcl-2 (two primary apoptosis regulating proteins). In conclusion, this study revealed that BP-3 had the potential to perturb the Sertoli cell barrier through altered junction proteins and disorganized F-actin, but it could hardly evoke Sertoli cell apoptosis.
Topics: Actins; Animals; Apoptosis; Benzophenones; Blood-Testis Barrier; Male; Mice; Rats; Rats, Sprague-Dawley; Sertoli Cells; Spermatogenesis; Tight Junctions
PubMed: 34558770
DOI: 10.1002/tox.23375