scholarly journals Functional Importance of 1α,25(OH)2-Vitamin D3 and the Identification of Its Nongenomic and Genomic Signaling Pathways in the Testis

2014 ◽  
Vol 2014 ◽  
pp. 1-10 ◽  
Author(s):  
Fátima Regina Mena Barreto Silva
Keyword(s):  
Calcium Binding ◽  
Cellular Proliferation ◽  
Reproductive Tract ◽  
Ionic Currents ◽  
Male Reproduction ◽  
Human Testis ◽  
Metabolizing Enzymes ◽  
Proliferation And Differentiation ◽  
Membrane Bound ◽  
Pka Pathway

The 1α,25(OH)2-vitamin D3 (1,25-D3) is known by its classic effects on Ca2+ metabolism and regulation of cellular proliferation and differentiation. The hormone 1,25-D3 acts in the testis through nongenomic and genomic events being implicated in the success of spermatogenesis in rats and in human being. The aim of this review was to highlight the effect and intracellular pathways of 1,25-D3 to modulate the spermatogenesis. The pivotal role of 1,25-D3 in male reproduction is reinforced by the presence of VDR and 1α-hydroxylase in reproductive tract. Also, the marked expression of VDR and the VD metabolizing enzymes in human testis, ejaculatory tract, and mature spermatozoa implicates the 1,25-D3 in spermatogenesis and maturation of human spermatozoa. Among genomic events, 1,25-D3 influences the expression of calcium binding protein and stimulates aromatase gene expression through a nongenomic activation of the membrane-bound VDR receptor involving the PKA pathway in the testis. Also, 1,25-D3 stimulates amino acid transport and exocytosis in testis by nongenomic events coupled to ionic currents triggered at plasma membrane. All together, the demonstration that 1,25-D3 regulates both Sertoli cell and sperm function may be useful for the study and development of new therapeutic strategies for the male reproductive disorders.

scholarly journals Immunoregulation in the testis and its implication in fertility and infections

2021 ◽  
Author(s):  
Kushaan Khambata ◽  
Deepak Modi ◽  
Satish Gupta
Keyword(s):  
Reproductive Tract ◽  
Viral Infections ◽  
The Body ◽  
Male Reproduction ◽  
Human Testis ◽  
Male Reproductive Tract ◽  
Inflammatory Conditions ◽  
Immunodeficiency Virus ◽  
Sperm Antigens ◽  
Sperm Antibodies

The testis is designated as one of the immune previleged sites in the body and harbours a unique immunoregulatory environment, which is important for preventing an immune response against sperm antigens which otherwise are recognized as “foreign” by the immune system. The blood-testis barrier along with the unique immune cells repertoire and various immunoregulatory & immunosuppressive factors secreted by the Leydig cells, Sertoli cells and peritubular cells act in concert to maintain the tolerogenic environment in the testis. Abberations in immunotolerant mechanisms in the testis can lead to generation of anti-sperm antibodies that have an association with male infertility. It can also lead to inflammatory conditions of the male reproductive tract manifested as epididymitis and orchitis, generally due to bacterial or viral infections. In addition, non-infectious epididymitis and orchitis, having autoimmune origin have also been reported in males. While the immune privilege status of human testis protects the germ cells from an immune attack, it can also make the testis a succeptible reservoir for viruses such as human immunodeficiency virus-1, Zika virus and severe acute respiratory syndrome coronavirus-2, all of which have adverse consequences on male reproduction.

Calcium transport in male reproduction is possibly influenced by vitamin D and CaSR

2021 ◽  
Author(s):  
Ida Marie Boisen ◽  
John Erik Nielsen ◽  
Lieve Verlinden ◽  
Mette Lorenzen ◽  
Rune Holt ◽  
...  
Keyword(s):  
Vitamin D ◽  
Calcium Transport ◽  
Calcium Concentration ◽  
Transient Receptor Potential ◽  
Reproductive Tract ◽  
Receptor Potential ◽  
Male Reproduction ◽  
Human Testis ◽  
Transient Receptor Potential Vanilloid ◽  
Male Reproductive Tract

Vitamin D is important for gonadal function in rodents, and improvement of vitamin D status in men with low sperm counts increases live birth rate. Vitamin D is a regulator of transcellular calcium transport in the intestine and kidney and may influence the dramatic changes in the luminal calcium concentration in epididymis. Here, we show spatial expression in the male reproductive tract of vitamin D receptor (VDR)-regulated factors involved in calcium transport: Transient receptor potential vanilloid 5/6 (TRPV5/6), sodium/calcium exchanger 1 (NCX1), plasma membrane calcium ATPase 1 (PMCA1), calbindin D9k, calcium-sensing receptor (CaSR), and parathyroid hormone-related peptide (PTHrP) in mouse and human testis and epididymis. Testicular Casr expression was lower in Vdr ablated mice compared with controls. Moreover, expression levels of Casr and Pthrp were strongly correlated in both testis and epididymis and Pthrp was suppressed by 1,25(OH)2D3 in a spermatogonial cell line. The expression of CaSR in epididymis may be of greater importance than in the gonad in mice as germ cell-specific Casr deficient mice had no major reproductive phenotype, and coincubation with a CaSR-agonist had no effect on human sperm-oocyte binding. In humans, seminal calcium concentration between 5-10 mM was associated with a higher fraction of motile and morphologically normal sperm cells and the seminal calcium concentration was not associated with serum calcium levels. In conclusion, VDR regulates CaSR and PTHrP, and both factors may be involved in the regulation of calcium transport in the male reproductive tract with possible implications for sperm function and storage.

MAPK Cascades in Cell Growth and Death

Physiology ◽  
1997 ◽  
Vol 12 (6) ◽  
pp. 286-293 ◽  
Author(s):  
JT Neary
Keyword(s):  
Gene Expression ◽  
Signal Transduction ◽  
Cellular Proliferation ◽  
Inflammatory Diseases ◽  
Growth Arrest ◽  
Therapeutic Strategies ◽  
Extracellular Signals ◽  
Mapk Cascades ◽  
Proliferation And Differentiation ◽  
Signaling Components

Distinct signal transduction cascades comprised of at least three proteinkinases mediate cellular proliferation and differentiation, growth arrest, and programmed cell death. These cytosolic enzymes relay extracellular signals from cell surface to nucleus, leading to changes in gene expression. Signaling components of these cascades offer new possibilities for therapeutic strategies in tumorigenesis, inflammatory diseases, immunopotentiation, wound healing, and regeneration.

scholarly journals Regulatory links between imprinted genes: evolutionary predictions and consequences

2016 ◽  
Vol 283 (1824) ◽  
pp. 20152760 ◽  
Author(s):  
Manus M. Patten ◽  
Michael Cowley ◽  
Rebecca J. Oakey ◽  
Robert Feil
Keyword(s):  
Gene Networks ◽  
Cellular Proliferation ◽  
Point Of View ◽  
Imprinted Genes ◽  
Imprinted Gene ◽  
Genome Wide ◽  
Proliferation And Differentiation ◽  
Evolutionary View ◽  
In Trans ◽  
Regulatory Effects

Genomic imprinting is essential for development and growth and plays diverse roles in physiology and behaviour. Imprinted genes have traditionally been studied in isolation or in clusters with respect to cis -acting modes of gene regulation, both from a mechanistic and evolutionary point of view. Recent studies in mammals, however, reveal that imprinted genes are often co-regulated and are part of a gene network involved in the control of cellular proliferation and differentiation. Moreover, a subset of imprinted genes acts in trans on the expression of other imprinted genes. Numerous studies have modulated levels of imprinted gene expression to explore phenotypic and gene regulatory consequences. Increasingly, the applied genome-wide approaches highlight how perturbation of one imprinted gene may affect other maternally or paternally expressed genes. Here, we discuss these novel findings and consider evolutionary theories that offer a rationale for such intricate interactions among imprinted genes. An evolutionary view of these trans -regulatory effects provides a novel interpretation of the logic of gene networks within species and has implications for the origin of reproductive isolation between species.

scholarly journals Cellular Functions of OCT-3/4 Regulated by Ubiquitination in Proliferating Cells

Cancers ◽  
2020 ◽  
Vol 12 (3) ◽  
pp. 663
Author(s):  
Kwang-Hyun Baek ◽  
Jihye Choi ◽  
Chang-Zhu Pei
Keyword(s):  
Stem Cells ◽  
Cellular Proliferation ◽  
Critical Role ◽  
Embryonic Stem ◽  
Cell Types ◽  
Ubiquitin Proteasome System ◽  
Specific Cell ◽  
Cellular Mechanisms ◽  
Proliferating Cells ◽  
Proliferation And Differentiation

Octamer-binding transcription factor 3/4 (OCT-3/4), which is involved in the tumorigenesis of somatic cancers, has diverse functions during cancer development. Overexpression of OCT-3/4 has been detected in various human somatic tumors, indicating that OCT-3/4 activation may contribute to the development and progression of cancers. Stem cells can undergo self-renewal, pluripotency, and reprogramming with the help of at least four transcription factors, OCT-3/4, SRY box-containing gene 2 (SOX2), Krüppel-like factor 4 (KLF4), and c-MYC. Of these, OCT-3/4 plays a critical role in maintenance of undifferentiated state of embryonic stem cells (ESCs) and in production of induced pluripotent stem cells (iPSCs). Stem cells can undergo partitioning through mitosis and separate into specific cell types, three embryonic germ layers: the endoderm, the mesoderm, and the trophectoderm. It has been demonstrated that the stability of OCT-3/4 is mediated by the ubiquitin-proteasome system (UPS), which is one of the key cellular mechanisms for cellular homeostasis. The framework of the mechanism is simple, but the proteolytic machinery is complicated. Ubiquitination promotes protein degradation, and ubiquitination of OCT-3/4 leads to regulation of cellular proliferation and differentiation. Therefore, it is expected that OCT-3/4 may play a key role in proliferation and differentiation of proliferating cells.

scholarly journals Oxidative Stress, Testicular Inflammatory Pathways and Male Reproduction

2021 ◽  
Vol 22 (18) ◽  
pp. 10043
Author(s):  
Sulagna Dutta ◽  
Pallav Sengupta ◽  
Petr Slama ◽  
Shubhadeep Roychoudhury
Keyword(s):  
Oxidative Stress ◽  
Male Infertility ◽  
Reproductive Tract ◽  
Inflammatory Responses ◽  
Male Reproduction ◽  
Male Reproductive Tract ◽  
Proinflammatory Mediators ◽  
Global Issue ◽  
Causative Factors ◽  
Infertility Patients

Inflammation is among the core causatives of male infertility. Despite male infertility being a serious global issue, “bits and pieces” of its complex etiopathology still remain missing. During inflammation, levels of proinflammatory mediators in the male reproductive tract are greater than usual. According to epidemiological research, in numerous cases of male infertility, patients suffer from acute or chronic inflammation of the genitourinary tract which typically occurs without symptoms. Inflammatory responses in the male genital system are inextricably linked to oxidative stress (OS). OS is detrimental to male fertility parameters as it causes oxidative damage to reproductive cells and intracellular components. Multifarious male infertility causative factors pave the way for impairing male reproductive functions via the common mechanisms of OS and inflammation, both of which are interlinked pathophysiological processes, and the occurrence of any one of them induces the other. Both processes may be simultaneously found in the pathogenesis of male infertility. Thus, the present article aims to explain the role of inflammation and OS in male infertility in detail, as well as to show the mechanistic pathways that link causative factors of male reproductive tract inflammation, OS induction, and oxidant-sensitive cellular cascades leading to male infertility.

Hmgb3 Induces the Differentiation of Uterine Stromal Cells Through Targeting Ptn

2018 ◽  
Vol 26 (7) ◽  
pp. 891-899
Author(s):  
Kai Wang ◽  
Yun-Hou Yin ◽  
Zhan-Qing Yang ◽  
Hai-Fan Yu ◽  
Yu-Si Wang ◽  
...  
Keyword(s):  
Stromal Cells ◽  
Messenger Rna ◽  
Cellular Proliferation ◽  
Physiological Role ◽  
High Mobility ◽  
Ovariectomized Mice ◽  
Dynamic Expression ◽  
Proliferation And Differentiation ◽  
Reliable Marker

Uterine decidualization is crucial for placenta formation and pregnancy maintenance. Although previous studies have reported that high mobility group box 3 (Hmgb3) is involved in the regulation of cellular proliferation and differentiation, little is known regarding its physiological role in uterine decidualization. Here, in situ hybridization result exhibited a dynamic expression pattern of Hmgb3 messenger RNA (mRNA) during early gestation, and it was mainly localized to the decidua on days 6 to 8 of gestation. Consistently, elevated Hmgb3 expression was noted in the decidualizing stromal cells after intraluminal oil infusion. In uterine luminal epithelium of ovariectomized mice, estrogen induced the accumulation of Hmgb3 mRNA, which was dependent on the existence of implanting blastocyst. Simultaneously, Hmgb3 could stimulate the proliferation of uterine stromal cells and promote the expression of Prl8a2, a reliable marker for stromal cell differentiation. Further analysis evidenced that Hmgb3 might modulate the expression of pleiotropin (Ptn) in uterine stromal cells. Moreover, silencing of Ptn could impede the upregulation of Prl8a2 elicited by Hmgb3 overexpression, while overexpression of Ptn reversed the repressive effects of Hmgb3 siRNA on Prl8a2 expression. Collectively, Hmgb3 may direct uterine decidualization through targeting Ptn.

scholarly journals Analysis of cell-biomaterial interaction through cellular bridge formation in the interface between hGMSCs and CaP bioceramics

2020 ◽  
Vol 10 (1) ◽  
Author(s):  
Isabel Benjumeda Wijnhoven ◽  
Raúl Vallejos ◽  
Juan F. Santibanez ◽  
Carola Millán ◽  
Juan F. Vivanco
Keyword(s):  
Stem Cells ◽  
Osteogenic Differentiation ◽  
Bone Tissue ◽  
Cellular Networks ◽  
Cellular Proliferation ◽  
Cell Behaviour ◽  
Proliferation And Differentiation ◽  
Biological Performance ◽  
Regenerative Therapies

Abstract The combination of biomaterials and stem cells for clinical applications constitute a great challenge in bone tissue engineering. Hence, cellular networks derived from cells-biomaterials crosstalk have a profound influence on cell behaviour and communication, preceding proliferation and differentiation. The purpose of this study was to investigate in vitro cellular networks derived from human gingival mesenchymal stem cells (hGMSCs) and calcium phosphate (CaP) bioceramic interaction. Biological performance of CaP bioceramic and hGMSCs interaction was evaluated through cell adhesion and distribution, cellular proliferation, and potential osteogenic differentiation, at three different times: 5 h, 1 week and 4 weeks. Results confirmed that hGMSCs met the required MSCs criteria while displaying osteogenic differentiaton capacities. We found a significant increase of cellular numbers and proliferation levels. Also, protein and mRNA OPN expression were upregulated in cells cultured with CaP bioceramic by day 21, suggesting an osteoinductible effect of the CaP bioceramic on hGMSCs. Remarkably, CaP bioceramic aggregations were obtained through hGMSCs bridges, suggesting the in vitro potential of macrostructures formation. We conclude that hGMSCs and CaP bioceramics with micro and macropores support hGMSC adhesion, proliferation and osteogenic differentiation. Our results suggest that investigations focused on the interface cells-biomaterials are essential for bone tissue regenerative therapies.

scholarly journals The Impact of Cellular Proliferation on the HIV-1 Reservoir

Viruses ◽  
2020 ◽  
Vol 12 (2) ◽  
pp. 127
Author(s):  
Maria C. Virgilio ◽  
Kathleen L. Collins
Keyword(s):  
Cellular Proliferation ◽  
Integration Site ◽  
Infected Individual ◽  
Host Cells ◽  
Viral Reservoir ◽  
Proliferative Potential ◽  
Proliferation And Differentiation ◽  
Latently Infected ◽  
Infected Cells ◽  
The Impact

Human immunodeficiency virus (HIV) is a chronic infection that destroys the immune system in infected individuals. Although antiretroviral therapy is effective at preventing infection of new cells, it is not curative. The inability to clear infection is due to the presence of a rare, but long-lasting latent cellular reservoir. These cells harboring silent integrated proviral genomes have the potential to become activated at any moment, making therapy necessary for life. Latently-infected cells can also proliferate and expand the viral reservoir through several methods including homeostatic proliferation and differentiation. The chromosomal location of HIV proviruses within cells influences the survival and proliferative potential of host cells. Proliferating, latently-infected cells can harbor proviruses that are both replication-competent and defective. Replication-competent proviral genomes contribute to viral rebound in an infected individual. The majority of available techniques can only assess the integration site or the proviral genome, but not both, preventing reliable evaluation of HIV reservoirs.

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