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Andrology Jul 2020Testicular architecture and sperm production are supported by a complex network of communication between various cell types. These signals ensure fertility by:... (Review)
Review
BACKGROUND
Testicular architecture and sperm production are supported by a complex network of communication between various cell types. These signals ensure fertility by: regulating spermatogonial stem/progenitor cells; promoting steroidogenesis; and driving male-specific differentiation of the gonad. Sertoli cells have long been assumed to be the major cellular player in testis organogenesis and spermatogenesis. However, cells in the interstitial compartment, such as Leydig, vascular, immune, and peritubular cells, also play prominent roles in the testis but are less well understood.
OBJECTIVES
Here, we aim to outline our current knowledge of the cellular and molecular mechanisms by which interstitial cell types contribute to spermatogenesis and testicular development, and how these diverse constituents of the testis play essential roles in ensuring male sexual differentiation and fertility.
METHODS
We surveyed scientific literature and summarized findings in the field that address how interstitial cells interact with other interstitial cell populations and seminiferous tubules (i.e., Sertoli and germ cells) to support spermatogenesis, male-specific differentiation, and testicular function. These studies focused on 4 major cell types: Leydig cells, vascular cells, immune cells, and peritubular cells.
RESULTS AND DISCUSSION
A growing number of studies have demonstrated that interstitial cells play a wide range of functions in the fetal and adult testis. Leydig cells, through secretion of hormones and growth factors, are responsible for steroidogenesis and progression of spermatogenesis. Vascular, immune, and peritubular cells, apart from their traditionally acknowledged physiological roles, have a broader importance than previously appreciated and are emerging as essential players in stem/progenitor cell biology.
CONCLUSION
Interstitial cells take part in complex signaling interactions with both interstitial and tubular cell populations, which are required for several biological processes, such as steroidogenesis, Sertoli cell function, spermatogenesis, and immune regulation. These various processes are essential for testicular function and demonstrate how interstitial cells are indispensable for male fertility.
Topics: Animals; Humans; Leydig Cells; Male; Organogenesis; Spermatogenesis; Testis
PubMed: 31444950
DOI: 10.1111/andr.12703 -
International Journal of Molecular... Oct 2020The renin-angiotensin system (RAS) is a peptidic system known mainly for its roles in the maintenance of blood pressure and electrolyte and fluid homeostasis. However,... (Review)
Review
The renin-angiotensin system (RAS) is a peptidic system known mainly for its roles in the maintenance of blood pressure and electrolyte and fluid homeostasis. However, several tissues and cells have been described to possess an intrinsic RAS that acts locally through different paracrine and autocrine mechanisms. In the male reproductive system, several components of this system have been observed in various organs and tissues, such as the testes, spermatozoa and seminal fluid. Some functions attributed to this local RAS are maintenance of seminal plasma electrolytes, regulation of steroidogenesis and spermatogenesis, and sperm functions. However, their specific actions in these locations are not fully understood. Therefore, a deep knowledge of the functions of the RAS at both the testicular and seminal levels could clarify its roles in male infertility and sperm physiology, and the different RAS elements could be used to design tools enabling the diagnosis and/or treatment of male infertility.
Topics: Humans; Infertility, Male; Male; Renin-Angiotensin System; Semen; Spermatogenesis; Spermatozoa; Testis
PubMed: 33114706
DOI: 10.3390/ijms21217943 -
Journal of Veterinary Diagnostic... Nov 2022A 9-mo-old, male domestic shorthair cat was presented for castration because of mounting behavior observed by the owner. On physical examination, the cat was bilaterally...
A 9-mo-old, male domestic shorthair cat was presented for castration because of mounting behavior observed by the owner. On physical examination, the cat was bilaterally cryptorchid, but had penile spines. Abdominal exploration through a midline laparotomy revealed 2 pairs of masses. All 4 masses had gross features of testes, and ranged from 7 × 5 × 5 mm to 12 × 6 × 7 mm, with associated epididymal tissue. Histologically, each mass contained seminiferous tubules consistent with testicular tissue, and epididymal tubules, confirming a diagnosis of polyorchidism; deferent ducts were not found. There was no evidence of neoplastic, infectious, or inflammatory disease. Mounting behavior ceased 4 wk post-surgery. Histologic confirmation of more than 2 testes is needed to establish a diagnosis of polyorchidism, a rare congenital anomaly that has been reported infrequently in the veterinary literature; reports have been of animals with triorchidism, with the exception of 1 cat with 4 intraabdominal testes. Our report emphasizes that, although rare, polyorchidism should be considered in cryptorchid cats, or whenever penile spines are present in a previously castrated cat. Our case also highlights the value of checking for penile spines in a bilaterally cryptorchid cat if abdominal ultrasound is not an option to aid in surgical planning.
Topics: Cats; Male; Animals; Cryptorchidism; Testis; Orchiectomy; Ultrasonography; Epididymis; Cat Diseases
PubMed: 36184931
DOI: 10.1177/10406387221127883 -
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 -
Nature Communications Dec 2022Seminiferous tubules (STs) in the mammalian testes are connected to the rete testis (RT) via a Sertoli valve (SV). Spermatozoa produced in the STs are released into the...
Seminiferous tubules (STs) in the mammalian testes are connected to the rete testis (RT) via a Sertoli valve (SV). Spermatozoa produced in the STs are released into the tubular luminal fluid and passively transported through the SV into the RT. However, the physiological functions of the RT and SV remain unclear. Here, we identified the expression of Sox17 in RT epithelia. The SV valve was disrupted before puberty in RT-specific Sox17 conditional knockout (Sox17-cKO) male mice. This induced a backflow of RT fluid into the STs, which caused aberrant detachment of immature spermatids. RT of Sox17-cKO mice had reduced expression levels of various growth factor genes, which presumably support SV formation. When transplanted next to the Sox17 RT, Sertoli cells of Sox17-cKO mice reconstructed the SV and supported proper spermiogenesis in the STs. This study highlights the novel and unexpected modulatory roles of the RT in SV valve formation and spermatogenesis in mouse testes, as a downstream action of Sox17.
Topics: Animals; Male; Mice; Epithelium; HMGB Proteins; Mammals; Mice, Knockout; Rete Testis; Sertoli Cells; Sexual Maturation; SOXF Transcription Factors; Spermatogenesis; Testis
PubMed: 36543770
DOI: 10.1038/s41467-022-35465-1 -
Andrology Jul 2021The testes are suspected target organs of SARS-CoV-2. However, the results of studies on the effect of COVID-19 on male reproduction are controversial. (Review)
Review
BACKGROUND
The testes are suspected target organs of SARS-CoV-2. However, the results of studies on the effect of COVID-19 on male reproduction are controversial.
OBJECTIVE
To summarize current research on the effects of COVID-19 on male reproduction.
METHODS
A systematic review of English literature was performed using PubMed and Ovid Embase up to 18 August 2020. Research articles on the presence of SARS-CoV-2 in semen, the effects of the virus on semen parameters and any pathological changes in the testes were evaluated.
RESULTS
Fourteen studies were included in this review. Six of 176 survivors (3.4%) and 1 of 13 decedents (7.7%) in 2 of 12 studies were positive for viral RNA in semen and testicular tissue, respectively. After stratification of patient groups, we found that the virus was detected in the relatively early stage of infection, 6-16 days after disease onset, in semen from survivors. Two of 3 studies reported that some participants had substandard semen quality after COVID-19, and 1 study found that COVID-19 may impair semen quality in a severity-related manner. Pathological analyses showed that injuries to the seminiferous tubule occurred in all decedents (N = 11). Another study found that orchitic and testis fibrin microthrombi occurred in patients with fatal disease (100%, N = 2). Scrotal discomfort of orchiepididymitis or spermatic cord inflammation has also been reported in COVID-19 patients.
CONCLUSION
Current studies suggest that semen is rarely considered a carrier of SARS-CoV-2 genetic material during the infection period but not in the semen of recovered patients. Fatal COVID-19 may cause testicular structure damage without the presence of virus.
Topics: COVID-19; Humans; Male; Reproduction; Semen; Semen Analysis; Seminiferous Tubules; Testis
PubMed: 33427404
DOI: 10.1111/andr.12970 -
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 -
Andrology Mar 2023Men with Klinefelter Syndrome develop some degree of seminiferous tubule degeneration, hyalinization, and fibrosis by adulthood. However, the pathophysiology surrounding... (Review)
Review
BACKGROUND
Men with Klinefelter Syndrome develop some degree of seminiferous tubule degeneration, hyalinization, and fibrosis by adulthood. However, the pathophysiology surrounding testicular fibrosis in Klinefelter Syndrome patients remains incompletely understood.
OBJECTIVES
To perform a systematic review of literature studying the mechanisms of fibrosis initiation or propagation in Klinefelter Syndrome testes.
MATERIALS/METHODS
PubMed was searched systematically for articles specific to Klinefelter Syndrome and the process of fibrosis. Articles that did not contain original data or specifically addressed the target material were excluded. Additional references were extracted when pertinent from the reference lists of included studies.
RESULTS
Primary search yielded 139 articles for abstract review, which was narrowed to 16 for full-text review. Following full-text review, eight contained original data and met topic criteria, with one paper added from reference review for a total of nine papers.
DISCUSSION
The date range for included papers was 1992-2022. The proposed mechanisms of fibrosis mainly were centered around the impact of altered Sertoli cells on germ cells, the hormonal impact on Leydig cells, the inflammation mediated by mast cells, or the fibrous extracellular matrix deposition by peritubular myoid cells. Additionally, discussions of the role of the altered microvasculature and the specific proteins involved in the blood-testis barrier or the seminiferous tubule architecture are reviewed. Recent papers have incorporated advanced sequencing and offer future directions for targeted gene expression analysis. Still, much of the published data consists solely of immunohistological assessment by age range, creating difficulties in extrapolating causality.
CONCLUSION
The specific initiating factors of fibrosis of the seminiferous tubules and the propagation mechanisms unique to Klinefelter Syndrome remain incompletely understood with a relative paucity of data. Nonetheless, academic interest is increasing in this field as it may further elucidate the pathophysiology behind Klinefelter syndrome.
Topics: Male; Humans; Adult; Klinefelter Syndrome; Testis; Seminiferous Tubules; Sertoli Cells; Fibrosis
PubMed: 36252136
DOI: 10.1111/andr.13327 -
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 -
International Braz J Urol : Official... 2022To analyze the incidence of epididymal anomalies (EAs) associated to spermatic obstruction in patients with undescended testis (UT) according to testicular position and...
BACKGROUND
To analyze the incidence of epididymal anomalies (EAs) associated to spermatic obstruction in patients with undescended testis (UT) according to testicular position and age.
MATERIALS AND METHODS
We studied 87 patients (110 testis) with cryptorchidism and analyzed the presence of EAs correlated with the testicular position, age and patency of the processus vaginalis (PV). To analyze the relations between the testis and epididymis we considered three situations: (a) Normal pattern: the epididymis was attached to the testis at the head and tail and epididymis totally attached to the testis; (b) EAs: when the epididymis was attached to the testis only at the head (Figure-1A) and (c) EAs associated to spermatic obstruction: epididymis was attached to the testis only at the tail (Figure-1B) and when there are no visible connection between testis and epididymis (Figure-1C). We used the Wilcoxon-Mann-Whitney test and the Chi-square test for contingency analysis (p <0.05).
RESULTS
The mean age of the patients was 5.18 years (SD=2.867). Of 110 testes analyzed, 14 were abdominal (12.72%); 83 inguinal (75.45%) and 13 suprascrotal (11.81%). Normal relationships between testis and epididymis were observed in 54 patients (62.1%) with no significant differences in relation to the patient's age (p=0.666). Epididymal tail disjunction was observed in 23 patients (26.44%), with no significant differences in relation to age (p=0.59). EAs associated to spermatic obstruction were observed in 16 patients (18.4%), also with no significant differences in relation to age (p=0.684). We did not observe significant correlation between the testis position and the incidence of EAs (p=0.119). We did not observe significant correlations between patency of the PV (64.7%) and incidence of EAs (p=0.742).
CONCLUSIONS
Epididymal anomalies associated with spermatic obstruction are present in almost 20% of undescended testes, without significant correlation with age, testicular position and patency of the PV. This information needs to be correlated to the infertility risk of this congenital anomaly.
Topics: Child, Preschool; Cryptorchidism; Epididymis; Humans; Incidence; Inguinal Canal; Male; Testis
PubMed: 35170897
DOI: 10.1590/S1677-5538.IBJU.2022.99.07