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Physiological Reviews Jan 2016Mammalian spermatogenesis requires a stem cell pool, a period of amplification of cell numbers, the completion of reduction division to haploid cells (meiosis), and the... (Review)
Review
Mammalian spermatogenesis requires a stem cell pool, a period of amplification of cell numbers, the completion of reduction division to haploid cells (meiosis), and the morphological transformation of the haploid cells into spermatozoa (spermiogenesis). The net result of these processes is the production of massive numbers of spermatozoa over the reproductive lifetime of the animal. One study that utilized homogenization-resistant spermatids as the standard determined that human daily sperm production (dsp) was at 45 million per day per testis (60). For each human that means ā¼1,000 sperm are produced per second. A key to this level of gamete production is the organization and architecture of the mammalian testes that results in continuous sperm production. The seemingly complex repetitious relationship of cells termed the "cycle of the seminiferous epithelium" is driven by the continuous commitment of undifferentiated spermatogonia to meiosis and the period of time required to form spermatozoa. This commitment termed the A to A1 transition requires the action of retinoic acid (RA) on the undifferentiated spermatogonia or prospermatogonia. In stages VII to IX of the cycle of the seminiferous epithelium, Sertoli cells and germ cells are influenced by pulses of RA. These pulses of RA move along the seminiferous tubules coincident with the spermatogenic wave, presumably undergoing constant synthesis and degradation. The RA pulse then serves as a trigger to commit undifferentiated progenitor cells to the rigidly timed pathway into meiosis and spermatid differentiation.
Topics: Animals; Cell Lineage; Cell Proliferation; Humans; Male; Meiosis; Morphogenesis; Signal Transduction; Spermatogenesis; Spermatozoa; Stem Cells; Testis; Tretinoin
PubMed: 26537427
DOI: 10.1152/physrev.00013.2015 -
Scientific Data Sep 2018Spermatogenesis is an efficient and complex system of continuous cell differentiation. Previous studies investigating the transcriptomes of different cell populations in...
Spermatogenesis is an efficient and complex system of continuous cell differentiation. Previous studies investigating the transcriptomes of different cell populations in the testis relied either on sorting cells, cell depletion, or juvenile animals where not all stages of spermatogenesis have been completed. We present single-cell RNA sequencing (scRNA-Seq) data of 2,500 cells from the testes of two 8-week-old C57Bl/6J mice. Our dataset includes all spermatogenic stages from preleptotene to condensing spermatids as well as individual spermatogonia, Sertoli and Leydig cells. The data capture the full continuity of the meiotic and postmeiotic stages of spermatogenesis, and is thus ideally suited for marker discovery, network inference and similar analyses for which temporal ordering of differentiation processes can be exploited. Furthermore, it can serve as a reference for future studies involving single-cell RNA-Seq in mice where spermatogenesis is perturbed.
Topics: Animals; Leydig Cells; Male; Mice; Mice, Inbred C57BL; RNA; Sequence Analysis, RNA; Single-Cell Analysis; Spermatids; Spermatogenesis; Spermatogonia; Testis
PubMed: 30204153
DOI: 10.1038/sdata.2018.192 -
Cell Reports Feb 2019Spermatogenesis has been intensely studied in rodents but remains poorly understood in humans. Here, we used single-cell RNA sequencing to analyze human testes....
Spermatogenesis has been intensely studied in rodents but remains poorly understood in humans. Here, we used single-cell RNA sequencing to analyze human testes. Clustering analysis of neonatal testes reveals several cell subsets, including cell populations with characteristics of primordial germ cells (PGCs) and spermatogonial stem cells (SSCs). In adult testes, we identify four undifferentiated spermatogonia (SPG) clusters, each of which expresses specific marker genes. We identify protein markers for the most primitive SPG state, allowing us to purify this likely SSC-enriched cell subset. We map the timeline of male germ cell development from PGCs through fetal germ cells to differentiating adult SPG stages. We also define somatic cell subsets in both neonatal and adult testes and trace their developmental trajectories. Our data provide a blueprint of the developing human male germline and supporting somatic cells. The PGC-like and SSC markers areĀ candidates to be used for SSC therapy to treat infertility.
Topics: Adult; Cell Differentiation; Cells, Cultured; Humans; Infant, Newborn; Male; Single-Cell Analysis; Spermatogonia; Testis
PubMed: 30726734
DOI: 10.1016/j.celrep.2019.01.045 -
Genes Sep 2021As in other vertebrates, avian testes are the site of spermatogenesis and androgen production. The paired testes of birds differentiate during embryogenesis, first... (Review)
Review
As in other vertebrates, avian testes are the site of spermatogenesis and androgen production. The paired testes of birds differentiate during embryogenesis, first marked by the development of pre-Sertoli cells in the gonadal primordium and their condensation into seminiferous cords. Germ cells become enclosed in these cords and enter mitotic arrest, while steroidogenic Leydig cells subsequently differentiate around the cords. This review describes our current understanding of avian testis development at the cell biology and genetic levels. Most of this knowledge has come from studies on the chicken embryo, though other species are increasingly being examined. In chicken, testis development is governed by the Z-chromosome-linked gene, which directly or indirectly activates the male factors, , and . Recent single cell RNA-seq has defined cell lineage specification during chicken testis development, while comparative studies point to deep conservation of avian testis formation. Lastly, we identify areas of future research on the genetics of avian testis development.
Topics: Animals; Birds; Cell Differentiation; Chickens; Embryo, Nonmammalian; Gene Expression Regulation, Developmental; Male; Sertoli Cells; Sex Determination Processes; Testis; Transcription Factors
PubMed: 34573441
DOI: 10.3390/genes12091459 -
Frontiers in Neural Circuits 2014
Topics: Animals; Humans; Inferior Colliculi; Nerve Net; Neurons
PubMed: 25346661
DOI: 10.3389/fncir.2014.00113 -
Frontiers in Neural Circuits 2022
Topics: Auditory Perception; Inferior Colliculi
PubMed: 35664460
DOI: 10.3389/fncir.2022.898646 -
Frontiers in Endocrinology 2022
Topics: Humans; Male; Spermatogenesis; Testis
PubMed: 35957828
DOI: 10.3389/fendo.2022.984409 -
Hearing Research Nov 2022Sensory processing is frequently conceptualized as a linear flow of information from peripheral receptors through hierarchically organized brain regions, ultimately... (Review)
Review
Sensory processing is frequently conceptualized as a linear flow of information from peripheral receptors through hierarchically organized brain regions, ultimately reaching the cortex. In reality, this ascending stream is accompanied by massive descending connections that cascade from the cortex toward more peripheral subcortical structures. In the central auditory system, these feedback connections influence information processing at virtually every level of the pathway, including the thalamus, midbrain, and brainstem, and exert influence even at the level of the cochlea. The auditory cortico-collicular system, which connects the auditory cortex to the auditory midbrain, mediates manifold functions ranging from tuning shifts to defense behavior. In this review, we first summarize recent findings regarding the anatomical organization and physiological properties of the auditory cortico-collicular pathway. We then highlight several new studies that show that this projection system mediates high-level cognitive processes, acoustico-motor behaviors, and auditory plasticity, and discuss the circuit mechanisms through which they are mediated. Finally, we discuss remaining unanswered questions regarding cortico-collicular circuitry and function and potential avenues for future exploration.
Topics: Acoustic Stimulation; Auditory Cortex; Auditory Pathways; Inferior Colliculi
PubMed: 35351323
DOI: 10.1016/j.heares.2022.108488 -
Hearing Research Apr 2016Tinnitus, the phantom perception of sound, is physiologically characterized by an increase in spontaneous neural activity in the central auditory system. However, as... (Review)
Review
Tinnitus, the phantom perception of sound, is physiologically characterized by an increase in spontaneous neural activity in the central auditory system. However, as tinnitus is often associated with hearing impairment, it is unclear how a decrease of afferent drive can result in central hyperactivity. In this review, we first assess methods for tinnitus induction and objective measures of the tinnitus percept in animal models. From animal studies, we discuss evidence that tinnitus originates in the cochlear nucleus (CN), and hypothesize mechanisms whereby hyperactivity may develop in the CN after peripheral auditory nerve damage. We elaborate how this process is likely mediated by plasticity of auditory-somatosensory integration in the CN: the circuitry in normal circumstances maintains a balance of auditory and somatosensory activities, and loss of auditory inputs alters the balance of auditory somatosensory integration in a stimulus timing dependent manner, which propels the circuit towards hyperactivity. Understanding the mechanisms underlying tinnitus generation is essential for its prevention and treatment. This article is part of a Special Issue entitled
. Topics: Acoustic Stimulation; Animals; Auditory Pathways; Auditory Perception; Auditory Threshold; Cochlear Nucleus; Evoked Potentials, Auditory, Brain Stem; Humans; Inferior Colliculi; Neuronal Plasticity; Somatosensory Cortex; Tinnitus
PubMed: 26074307
DOI: 10.1016/j.heares.2015.06.005 -
Drug Metabolism and Disposition: the... May 2023Transporters are involved in the movement of many physiologically important molecules across cell membranes and have a substantial impact on the pharmacological and... (Review)
Review
Transporters are involved in the movement of many physiologically important molecules across cell membranes and have a substantial impact on the pharmacological and toxicological effect of xenobiotics. Many transporters have been studied in the context of disposition to, or toxicity in, organs such as the kidney and liver; however, transporters in the testes are increasingly gaining recognition for their role in drug transport across the blood-testis barrier (BTB). The BTB is an epithelial membrane barrier formed by adjacent Sertoli cells (SCs) in the seminiferous tubules that form intercellular junctional complexes to protect developing germ cells from the external environment. Consequently, many charged or large polar molecules cannot cross this barrier without assistance from a transporter. SCs express a variety of drug uptake and efflux transporters to control the flux of endogenous and exogenous molecules across the BTB. Recent studies have identified several transport pathways in SCs that allow certain drugs to circumvent the human BTB. These pathways may exist in other species, such as rodents and nonhuman primates; however, there is (1) a lack of information on their expression and/or localization in these species, and (2) conflicting reports on localization of some transporters that have been evaluated in rodents compared with humans. This review outlines the current knowledge on the expression and localization of pharmacologically relevant drug transporters in human testes and calls attention to the insufficient and contradictory understanding of testicular transporters in other species that are commonly used in drug disposition and toxicity studies. SIGNIFICANCE STATEMENT: While the expression, localization, and function of many xenobiotic transporters have been studied in organs such as the kidney and liver, the characterization of transporters in the testes is scarce. This review summarizes the expression and localization of common pharmacologically-relevant transporters in human testes that have significant implications for the development of drugs that can cross the blood-testis barrier. Potential expression differences between humans and rodents highlighted here suggest rodents may be inappropriate for some testicular disposition and toxicity studies.
Topics: Animals; Humans; Male; Blood-Testis Barrier; Testis; Sertoli Cells; Membrane Transport Proteins; Biological Transport
PubMed: 36732077
DOI: 10.1124/dmd.122.001186