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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 -
La Pediatria Medica E Chirurgica :... Jun 2017Polyorchidism is an anomaly characterized by more than two gonads; triorchidism is the most common variant. Its management is controversial, mostly when surgical...
Polyorchidism is an anomaly characterized by more than two gonads; triorchidism is the most common variant. Its management is controversial, mostly when surgical treatment is occasional. CB, 14 year-old, came to the hospital due to right-sided testicular torsion. During surgery, testis was rotated and the contralateral testis, which presented as an anatomically continuum with a gonadic structure similar to the other testes but with a smaller diameter, was fixed. We performed biopsy on both left testes and decided to preserve the supernumerary one. Following the anatomic and functional classification of polyorchidism by Singer, preservation is justified on the grounds of the presence of a supernumerary testis that drains into the epididymis of the normal testis, merging into one single deferent duct (Singer Type 1). At biopsy, both testes had a valid spermatogenic asset. The diagnostic follow-up at 6 and 12 months did not show any pathological alteration. Diagnosis of polyorchidism is occasional. Its treatment varies depending on the site, dimension, and anatomy of the drainage system of the supernumerary testis. If the supernumerary testis is preserved, a standardized diagnostic follow-up is recommended.
Topics: Adolescent; Biopsy; Follow-Up Studies; Humans; Male; Spermatic Cord Torsion; Testis
PubMed: 28673075
DOI: 10.4081/pmc.2017.141 -
ELife Mar 2022Sensory systems must account for both contextual factors and prior experience to adaptively engage with the dynamic external environment. In the central auditory system,...
Sensory systems must account for both contextual factors and prior experience to adaptively engage with the dynamic external environment. In the central auditory system, neurons modulate their responses to sounds based on statistical context. These response modulations can be understood through a hierarchical predictive coding lens: responses to repeated stimuli are progressively decreased, in a process known as repetition suppression, whereas unexpected stimuli produce a prediction error signal. Prediction error incrementally increases along the auditory hierarchy from the inferior colliculus (IC) to the auditory cortex (AC), suggesting that these regions may engage in hierarchical predictive coding. A potential substrate for top-down predictive cues is the massive set of descending projections from the AC to subcortical structures, although the role of this system in predictive processing has never been directly assessed. We tested the effect of optogenetic inactivation of the auditory cortico-collicular feedback in awake mice on responses of IC neurons to stimuli designed to test prediction error and repetition suppression. Inactivation of the cortico-collicular pathway led to a decrease in prediction error in IC. Repetition suppression was unaffected by cortico-collicular inactivation, suggesting that this metric may reflect fatigue of bottom-up sensory inputs rather than predictive processing. We also discovered populations of IC units that exhibit repetition enhancement, a sequential increase in firing with stimulus repetition. Cortico-collicular inactivation led to a decrease in repetition enhancement in the central nucleus of IC, suggesting that it is a top-down phenomenon. Negative prediction error, a stronger response to a tone in a predictable rather than unpredictable sequence, was suppressed in shell IC units during cortico-collicular inactivation. These changes in predictive coding metrics arose from bidirectional modulations in the response to the standard and deviant contexts, such that the units in IC responded more similarly to each context in the absence of cortical input. We also investigated how these metrics compare between the anesthetized and awake states by recording from the same units under both conditions. We found that metrics of predictive coding and deviance detection differ depending on the anesthetic state of the animal, with negative prediction error emerging in the central IC and repetition enhancement and prediction error being more prevalent in the absence of anesthesia. Overall, our results demonstrate that the AC provides cues about the statistical context of sound to subcortical brain regions via direct feedback, regulating processing of both prediction and repetition.
Topics: Acoustic Stimulation; Animals; Auditory Cortex; Auditory Pathways; Auditory Perception; Inferior Colliculi; Mice; Optogenetics
PubMed: 35290181
DOI: 10.7554/eLife.73289 -
Seminars in Cell & Developmental Biology Nov 2016In adult mammalian testes, spermatogenesis is comprised of several discrete cellular events that work in tandem to support the transformation and differentiation of... (Review)
Review
In adult mammalian testes, spermatogenesis is comprised of several discrete cellular events that work in tandem to support the transformation and differentiation of diploid spermatogonia to haploid spermatids in the seminiferous epithelium during the seminiferous epithelial cycle. These include: self-renewal of spermatogonial stem cells via mitosis and their transformation into differentiated spermatogonia, meiosis I/II, spermiogenesis and the release of sperms at spermiation. Studies have shown that these cellular events are under precise and coordinated controls of multiple proteins and signaling pathways. These events are also regulated by polarity proteins that are known to confer classical apico-basal (A/B) polarity in other epithelia. Furthermore, spermatid development is likely supported by planar cell polarity (PCP) proteins since polarized spermatids are aligned across the plane of seminiferous epithelium in an orderly fashion, analogous to hair cells in the cochlea of the inner ear. Thus, the maximal number of spermatids can be packed and supported by a fixed population of differentiated Sertoli cells in the limited space of the seminiferous epithelium in adult testes. In this review, we briefly summarize recent findings regarding the role of PCP proteins in the testis. This information should be helpful in future studies to better understand the role of PCP proteins in spermatogenesis.
Topics: Animals; Cell Polarity; Humans; Male; Models, Biological; Proteins; Signal Transduction; Spermatogenesis; Testis
PubMed: 27108805
DOI: 10.1016/j.semcdb.2016.04.010 -
Cell Cycle (Georgetown, Tex.) 2021Expansion of the coding and regulatory capabilities of eukaryotic transcriptomes by alternative splicing represents one of the evolutionary forces underlying the... (Review)
Review
Expansion of the coding and regulatory capabilities of eukaryotic transcriptomes by alternative splicing represents one of the evolutionary forces underlying the increased structural complexity of metazoans. Brain and testes stand out as the organs that mostly exploit the potential of alternative splicing, thereby expressing the largest repertoire of splice variants. Herein, we will review organ-specific as well as common mechanisms underlying the high transcriptome complexity of these organs and discuss the impact exerted by this widespread alternative splicing regulation on the functionality and differentiation of brain and testicular cells.
Topics: Animals; Brain; Cell Differentiation; Humans; Male; RNA Splicing; Spermatogenesis; Testis; Transcriptome
PubMed: 33632061
DOI: 10.1080/15384101.2021.1889187 -
Neuroscience Jun 2015What do animals hear? While it remains challenging to adequately assess sensory perception in animal models, it is important to determine perceptual abilities in model... (Review)
Review
What do animals hear? While it remains challenging to adequately assess sensory perception in animal models, it is important to determine perceptual abilities in model systems to understand how physiological processes and plasticity relate to perception, learning, and cognition. Here we discuss hearing in rodents, reviewing previous and recent behavioral experiments querying acoustic perception in rats and mice, and examining the relation between behavioral data and electrophysiological recordings from the central auditory system. We focus on measurements of critical bands, which are psychoacoustic phenomena that seem to have a neural basis in the functional organization of the cochlea and the inferior colliculus. We then discuss how behavioral training, brain stimulation, and neuropathology impact auditory processing and perception.
Topics: Acoustic Stimulation; Animals; Auditory Cortex; Auditory Pathways; Auditory Perception; Cochlea; Inferior Colliculi; Mice; Models, Animal; Neuronal Plasticity; Perceptual Masking; Rats
PubMed: 25827498
DOI: 10.1016/j.neuroscience.2015.03.053 -
The Journal of the Acoustical Society... Nov 2019Circadian rhythms control the timing of all bodily functions, and misalignment in the rhythms can cause various diseases. Moreover, circadian rhythms are highly... (Review)
Review
Circadian rhythms control the timing of all bodily functions, and misalignment in the rhythms can cause various diseases. Moreover, circadian rhythms are highly conserved and are regulated by a transcriptional-translational feedback loop of circadian genes that has a periodicity of approximately 24 h. The cochlea and the inferior colliculus (IC) have been shown to possess an autonomous and self-sustained circadian system as demonstrated by recording, in real time, the bioluminescence from PERIOD2::LUCIFERASE (PER2::LUC) mice. The cochlea and IC both express the core clock genes, Per1, Per2, Bmal1, and Rev-Erbα, where RNA abundance is rhythmically distributed with a 24 h cycle. Noise exposure alters clock gene expression in the cochlea and the IC after noise stimulation, although in different ways. These findings highlight the importance of circadian responses in the cochlea and the IC and emphasize the importance of circadian mechanisms for understanding the differences in central and peripheral auditory function and the subsequent molecular changes that occur after daytime (inactive phase) or nighttime (active phase) noise trauma.
Topics: Activity Cycles; Animals; Circadian Clocks; Circadian Rhythm Signaling Peptides and Proteins; Cochlea; Inferior Colliculi; Noise
PubMed: 31795664
DOI: 10.1121/1.5132290 -
Development (Cambridge, England) Jul 2023Temporal transcription profiles of fetal testes with Sertoli cell ablation were examined in 4-day culture using a diphtheria toxin (DT)-dependent cell knockout system in...
Temporal transcription profiles of fetal testes with Sertoli cell ablation were examined in 4-day culture using a diphtheria toxin (DT)-dependent cell knockout system in AMH-TRECK transgenic (Tg) mice. RNA analysis revealed that ovarian-specific genes, including Foxl2, were ectopically expressed in DT-treated Tg testis explants initiated at embryonic days 12.5-13.5. FOXL2-positive cells were ectopically observed in two testicular regions: near the testicular surface epithelia and around its adjacent mesonephros. The surface FOXL2-positive cells, together with ectopic expression of Lgr5 and Gng13 (markers of ovarian cords), were derived from the testis epithelia/subepithelia, whereas another FOXL2-positive population was the 3βHSD-negative stroma near the mesonephros. In addition to high expression of Fgfr1/Fgfr2 and heparan sulfate proteoglycan (a reservoir for FGF ligand) in these two sites, exogenous FGF9 additives repressed DT-dependent Foxl2 upregulation in Tg testes. These findings imply retention of Foxl2 inducibility in the surface epithelia and peri-mesonephric stroma of the testicular parenchyma, in which certain paracrine signals, including FGF9 derived from fetal Sertoli cells, repress feminization in these two sites of the early fetal testis.
Topics: Mice; Animals; Male; Female; Sertoli Cells; Testis; Mice, Transgenic; Ovary; Fetus
PubMed: 37376880
DOI: 10.1242/dev.201660 -
Biochemistry. Biokhimiia Apr 2021The novel coronavirus disease-2019 (COVID-19) pandemic, caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), has been a major public health emergency... (Review)
Review
The novel coronavirus disease-2019 (COVID-19) pandemic, caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), has been a major public health emergency worldwide with over 118.27-million confirmed COVID-19 cases and 2.62-million deaths recorded, as of March 12, 2021. Although this disease primarily targets lungs, damages in other organs, such as heart, kidney, liver, and testis, may occur. Testis is the cornerstone of male reproduction, while reproductive health is the most valuable resource for continuity of the human race. Given the unique nature of SARS-CoV-2, the mechanisms of its impact on the testes have yet to be fully explored. Notably, coronaviruses have been found to invade target cells through the angiotensin-converting enzyme 2 receptor, which can be found in the respiratory, gastrointestinal, cardiovascular, urinary tract, and reproductive organs, such as testes. Coronavirus studies have suggested that testes might be a potential target for SARS-CoV-2 infection. The first etiopathogenic concept proposed by current hypotheses indicates that the virus can invade testes through the angiotensin-converting enzyme 2 receptor. Next, the activated inflammatory response in the testes, disease-associated fever, and COVID-19 medications might be implicated in testicular alterations. Although evidence regarding the presence of SARS-CoV-2 mRNA in semen remains controversial, this emphasizes the need for researchers to pay closer attention to sexually transmitted diseases and male fertility after recovering from COVID-19. In this review the latest updates regarding COVID-19-associated testicular dysfunction are summarized and possible pathogenic mechanisms are discussed.
Topics: Angiotensin-Converting Enzyme 2; COVID-19; Fertility; Humans; Male; Pandemics; SARS-CoV-2; Testis
PubMed: 33941061
DOI: 10.1134/S0006297921040015 -
Seminars in Cell & Developmental Biology Sep 2018In adult mammalian testes, spermatids, most notably step 17-19 spermatids in stage IV-VIII tubules, are aligned with their heads pointing toward the basement membrane... (Review)
Review
In adult mammalian testes, spermatids, most notably step 17-19 spermatids in stage IV-VIII tubules, are aligned with their heads pointing toward the basement membrane and their tails toward the tubule lumen. On the other hand, these polarized spermatids also align across the plane of seminiferous epithelium, mimicking planar cell polarity (PCP) found in other hair cells in cochlea (inner ear). This orderly alignment of developing spermatids during spermiogenesis is important to support spermatogenesis, such that the maximal number of developing spermatids can be packed and supported by a fixed population of differentiated Sertoli cells in the limited space of the seminiferous epithelium in adult testes. In this review, we provide emerging evidence to demonstrate spermatid PCP in the seminiferous epithelium to support spermatogenesis. We also review findings in the field regarding the biology of spermatid cellular polarity (e.g., head-tail polarity and apico-basal polarity) and its inter-relationship to spermatid PCP. Furthermore, we also provide a hypothetical concept on the importance of PCP proteins in endocytic vesicle-mediated protein trafficking events to support spermatogenesis through protein endocytosis and recycling.
Topics: Animals; Cell Polarity; Humans; Male; Sertoli Cells; Signal Transduction; Spermatids; Spermatogenesis; Testis
PubMed: 28923514
DOI: 10.1016/j.semcdb.2017.09.008