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1.
Reprod Toxicol ; : 108653, 2024 Jul 01.
Article in English | MEDLINE | ID: mdl-38960208

ABSTRACT

Doxorubicin (DOX) is a chemotherapy agent associated with adverse effects on male reproductive health. Chlorella vulgaris (ChV) is a potent natural antioxidant with promising applications in maintaining health and preventing oxidative stress-related diseases. The present study aimed to investigate the protective effect of ChV on DOX-induced testicular toxicity. Twenty-five Wistar rats (230 ± 20g) were randomly assigned to five groups (n = 5), including the control group, sham group (received normal saline by oral gavage daily and intraperitoneally (IP) once a week), DOX group (3mg/kg; once a week; IP), ChV group (300mg/kg/day; by oral gavage), and DOX (3mg/kg; once a week; IP) + ChV (300mg/kg/day; by oral gavage) group. After 8 weeks of treatment, the rats were euthanized and serum testosterone level, testes histomorphometry, gonadosomatic index (GSI), apoptotic gene expression, oxidative stress index, and sperm parameters were assessed. The results showed that DOX led to a significant decrease in histological indexes, testosterone level, GSI, sperm parameters, and Bcl-2 gene expression and increased expression of P-53 and Bax genes, and oxidative stress markers (P<0.05). The administration of ChV in the DOX+ChV group significantly improved testosterone levels, sperm parameters, testicular tissue apoptosis, antioxidant enzymes, and structural integrity of the testes (P<0.05). The findings suggest that the co-administration of ChV can be a promising therapeutic agent to reduce the adverse effects of DOX on male reproductive performance.

2.
Adv Protein Chem Struct Biol ; 141: 381-445, 2024.
Article in English | MEDLINE | ID: mdl-38960481

ABSTRACT

The role of motor proteins in supporting intracellular transports of vesicles and organelles in mammalian cells has been known for decades. On the other hand, the function of motor proteins that support spermatogenesis is also well established since the deletion of motor protein genes leads to subfertility and/or infertility. Furthermore, mutations and genetic variations of motor protein genes affect fertility in men, but also a wide range of developmental defects in humans including multiple organs besides the testis. In this review, we seek to provide a summary of microtubule and actin-dependent motor proteins based on earlier and recent findings in the field. Since these two cytoskeletons are polarized structures, different motor proteins are being used to transport cargoes to different ends of these cytoskeletons. However, their involvement in germ cell transport across the blood-testis barrier (BTB) and the epithelium of the seminiferous tubules remains relatively unknown. It is based on recent findings in the field, we have provided a hypothetical model by which motor proteins are being used to support germ cell transport across the BTB and the seminiferous epithelium during the epithelial cycle of spermatogenesis. In our discussion, we have highlighted the areas of research that deserve attention to bridge the gap of research in relating the function of motor proteins to spermatogenesis.


Subject(s)
Spermatogenesis , Testis , Humans , Male , Testis/metabolism , Animals , Molecular Motor Proteins/metabolism , Molecular Motor Proteins/genetics
3.
Front Pediatr ; 12: 1413099, 2024.
Article in English | MEDLINE | ID: mdl-38957775

ABSTRACT

Objective: The purpose of this study was to determine whether the presence of blind-ended vas deferens and spermatic vessels (VDSV) during laparoscopic exploration of non-palpable testes (NPT) indicates testicular absence or atrophy. Materials and methods: A retrospective analysis was conducted on clinical data of patients diagnosed with NPT and treated with surgical intervention at our center from April 2013-April 2023. The dataset encompassed information such as the children's age, affected side, size of the contralateral testis, surgical procedures employed, outcomes, and histopathological examination results. All patients underwent physical examination and ultrasonography preoperatively, followed by a combination of laparoscopic exploration and exploration through inguinal or scrotal incisions during surgery. Long-term follow-up was conducted postoperatively. Results: A total of 476 cases comprising 504 NPT were included in this study: 302 cases on the left side, 146 cases on the right side, and 28 cases bilaterally. All patients underwent surgical treatment within 6-126 months (median 13 months). During laparoscopic exploration, blind-ended VDSV were found in 90 testes (72 on the left side, 18 on the right side), while exploration through inguinal or scrotal incisions revealed 52 (57.8%) testicular nodules with atrophy, which were excised, leaving 38 (42.2%) without any findings. Histopathological examination of atrophic nodules revealed fibrosis as the most common finding in 41 cases (78.8%), followed by involvement of the vas deferens in 33 cases (63.5%), calcification in 24 cases (46.2%), epididymis in 23 cases (44.2%), and hemosiderin deposition in 7 cases (13.6%). Fibrosis, calcification, hemosiderin deposition, involvement of the vas deferens, and epididymis were found in combination in 47 specimens (90.4%). Seminiferous tubules (SNT) were found in 3 specimens (5.7%), and germ cells (GC) were found in 1 specimen (1.9%). Conclusion: The presence of blind-ended VDSV during laparoscopic exploration of NPT does not necessarily indicate testicular absence or disappearance. It is possible that atrophic testicular nodules are located within the inguinal canal or scrotum. This understanding contributes to the management of non-palpable testes. Considering their unpredictable malignant potential, we recommend excision.

4.
Zoology (Jena) ; 165: 126186, 2024 Jun 29.
Article in English | MEDLINE | ID: mdl-38964201

ABSTRACT

Osteoglossomorpha, the bony tongue fishes, show great variation in morphology, behavioural strategies, reproductive biology and gamete ultrastructure. The order Osteoglossiformes is the only vertebrate taxon, in which four types of sperm (monoflagellate, biflagellate and aflagellate aquasperm and the complex introsperm) have been described. It is also the only vertebrate lineage in which aflagellate spermatozoa exist. The aim of this study was to analyse the structure of the testis and the process of spermiogenesis in the mormyrid Campylomormyrus compressirostris during the breeding season using light and electron microscopy (transmission and scanning). Males of this species have a single testis of the anastomosing tubular type. The tubules of the anterior part of the testis contain cysts with developing germ cells, and this region is much wider than the posterior part, which consists of efferent ducts filled with sperm cells. The cysts are filled with single or mitotic spermatogonia, primary and secondary spermatocytes and early spermatids. At the stage of spermatids with fine granular chromatin, the cysts rupture and successive stages of spermatid differentiation take place in the testicular lumen; we therefore characterise this process as 'extracystic spermiogenesis'. Sperm development in C. compressirostris is extremely simple and involves chromatin condensation in the central region of the nucleus, a slight decrease in nuclear volume, the appearance of numerous vesicles in the cytoplasm that form a tubular-vesicular system at the base of the nucleus. Both centrioles and mitochondria are translocated to the peripheral region of the midpiece, which forms the opposite pole to the nucleus. There are many differences between the types of spermiogenesis described so far in teleosts and that found in C. compressirostris, including the loss of flagellum formation. This unique type of spermiogenesis is restricted to species of the families Mormyridae and Gymnarchidae, all of which possess aflagellate spermatozoa. Our data demonstrate that the spermatid differentiation and existence of the aflagellate spermatozoon are a unique phenomena not only among teleosts but also in the whole vertebrate lineage.

5.
Cancer Treat Res Commun ; 40: 100830, 2024 Jun 28.
Article in English | MEDLINE | ID: mdl-38964205

ABSTRACT

BACKGROUND: NY-ESO-1 and XAGE1 cancer/testis antigens elicit humoral and cellular immune responses in NSCLC patients. We aimed to predict clinical benefit with ICI monotherapy, using an automated immunoassay of NY-ESO-1/XAGE1 antibodies (Abs). METHODS: This study enrolled 99 NSCLC patients who received nivolumab after chemotherapy, including 21 patients harboring EGFR, ALK, or KRAS alterations. The cutoff value (10 units/mL) of NY-ESO-1 and XAGE1 Ab was determined based on Ab levels in non-malignant controls, and NY-ESO-1/XAGE1 Abs in NSCLC were measured before nivolumab. Differences in PFS and OS between the Ab-positive and Ab-negative groups were retrospectively analyzed using Cox regression analysis after applying inverse probability of treatment weighting (IPTW). RESULTS: NY-ESO-1/XAGE1 Abs were positive in 28 NSCLC, who responded more highly to nivolumab than the Ab-negatives (response rate 50.0% vs. 15.5 %, p < 0.0007). The IPTW-adjusted positives and negatives for NY-ESO-1/XAGE1 Abs were 24.5 and 70.2, respectively. The Ab-positives showed longer IPTW-adjusted PFS (HR = 0.59, 95 % CI: 0.39-0.90, p = 0.014) and IPTW-adjusted OS (HR = 0.51, 95 % CI: 0.32-0.81, p = 0.004) than the Ab-negatives. Among NSCLC harboring driver genes, the Ab-positives (n = 10) showed longer PFS (HR = 0.34, 95 % CI: 0.13-0.89, p = 0.029) and OS (HR = 0.27, 95 % CI: 0.098-0.75, p = 0.012) than the Ab-negatives (n = 11). CONCLUSION: Our immunoassay of NY-ESO-1/XAGE1 Abs is probably useful for predicting the clinical benefit with nivolumab in NSCLC, including those harboring driver genes. These results suggest that our immunoassay may be useful in ICI monotherapy for NSCLC.

6.
J Nanobiotechnology ; 22(1): 390, 2024 Jul 03.
Article in English | MEDLINE | ID: mdl-38961442

ABSTRACT

BACKGROUND: Zinc oxide nanoparticle (ZnO NP) is one of the metal nanomaterials with extensive use in many fields such as feed additive and textile, which is an emerging threat to human health due to widely distributed in the environment. Thus, there is an urgent need to understand the toxic effects associated with ZnO NPs. Although previous studies have found accumulation of ZnO NPs in testis, the molecular mechanism of ZnO NPs dominated a decline in male fertility have not been elucidated. RESULTS: We reported that ZnO NPs exposure caused testicular dysfunction and identified spermatocytes as the primary damaged site induced by ZnO NPs. ZnO NPs led to the dysfunction of spermatocytes, including impaired cell proliferation and mitochondrial damage. In addition, we found that ZnO NPs induced ferroptosis of spermatocytes through the increase of intracellular chelatable iron content and lipid peroxidation level. Moreover, the transcriptome analysis of testis indicated that ZnO NPs weakened the expression of miR-342-5p, which can target Erc1 to block the NF-κB pathway. Eventually, ferroptosis of spermatocytes was ameliorated by suppressing the expression of Erc1. CONCLUSIONS: The present study reveals a novel mechanism in that miR-342-5p targeted Erc1 to activate NF-κB signaling pathway is required for ZnO NPs-induced ferroptosis, and provide potential targets for further research on the prevention and treatment of male reproductive disorders related to ZnO NPs.


Subject(s)
Ferroptosis , MicroRNAs , NF-kappa B , Signal Transduction , Spermatocytes , Testis , Zinc Oxide , Male , Animals , Ferroptosis/drug effects , Spermatocytes/metabolism , Spermatocytes/drug effects , MicroRNAs/metabolism , MicroRNAs/genetics , Mice , Zinc Oxide/pharmacology , Zinc Oxide/chemistry , NF-kappa B/metabolism , Testis/metabolism , Testis/drug effects , Signal Transduction/drug effects , Metal Nanoparticles/chemistry , Lipid Peroxidation/drug effects , Cell Proliferation/drug effects
7.
Front Endocrinol (Lausanne) ; 15: 1392917, 2024.
Article in English | MEDLINE | ID: mdl-38966220

ABSTRACT

Biogenic amines are signaling molecules with multiple roles in the central nervous system and in peripheral organs, including the gonads. A series of studies indicated that these molecules, their biosynthetic enzymes and their receptors are present in the testis and that they are involved in the regulation of male reproductive physiology and/or pathology. This mini-review aims to summarize the current knowledge in this field and to pinpoint existing research gaps. We suggest that the widespread clinical use of pharmacological agonists/antagonists of these signaling molecules, calls for new investigations in this area. They are necessary to evaluate the relevance of biogenic amines for human male fertility and infertility, as well as the potential value of at least one of them as an anti-aging compound in the testis.


Subject(s)
Biogenic Amines , Testis , Humans , Biogenic Amines/metabolism , Male , Testis/metabolism , Animals , Signal Transduction , Infertility, Male/metabolism
8.
Tissue Cell ; 89: 102450, 2024 Jun 19.
Article in English | MEDLINE | ID: mdl-38941762

ABSTRACT

Exposure to the neonicotinoid insecticide, imidacloprid (IMI), causes reproductive toxicity in mammals and reptiles. However, reports on the effects of IMI on the gonads in birds are grossly lacking. Therefore, this study investigated the effects of pubertal exposure to IMI on the histology, ultrastructure, as well as the cytoskeletal proteins, desmin, smooth muscle actin and vimentin, of the gonads of Japanese quail (Coturnix coturnix japonica). Quails were randomly divided into four groups at 5 weeks of age. The control group was given only distilled water, whereas, the other three experimental groups, IMI was administered by oral gavage at 1.55, 3.1, and 6.2 mg/kg, twice per week for 4 weeks. Exposure to IMI doses of 3.1 and 6.2 mg/kg caused dose-dependent histopathological changes in the ovary and testis. In the ovary, accumulation of lymphocytes, degenerative changes, and necrosis with granulocyte infiltrations were observed, while in the testis, distorted seminiferous tubules, germ cell sloughing, vacuolisations, apoptotic bodies, autophagosomes, and mitochondrial damage were detected. These changes were accompanied by a decreased number of primary follicles (P ≤ 0.05) in the ovary and a decrease (P ≤ 0.05) in the epithelial height, luminal, and tubular diameters of seminiferous tubules at the two higher dosages. In addition, IMI had a negative effect on the immunostaining intensity of desmin, smooth muscle actin, and vimentin in the ovarian and testicular tissue. In conclusion, exposure to IMI during puberty can lead to a range of histopathological alterations in the gonads of Japanese quails, which may ultimately result in infertility.

9.
Differentiation ; 138: 100791, 2024 Jun 19.
Article in English | MEDLINE | ID: mdl-38941819

ABSTRACT

A Wt1 conditional deletion, nuclear red fluorescent protein (RFP) reporter allele was generated in the mouse by gene targeting in embryonic stem cells. Upon Cre-mediated recombination, a deletion allele is generated that expresses RFP in a Wt1-specific pattern. RFP expression was detected in embryonic and adult tissues known to express Wt1, including the kidney, mesonephros, and testis. In addition, RFP expression and WT1 co-localization was detected in the adult uterine stroma and myometrium, suggesting a role in uterine function. Crosses with Wnt7a-Cre transgenic mice that express Cre in the Müllerian duct epithelium activate Wt1-directed RFP expression in the epithelium of the oviduct but not the stroma and myometrium of the uterus. This new mouse strain should be a useful resource for studies of Wt1 function and marking Wt1-expressing cells.

10.
Cryobiology ; : 104936, 2024 Jun 26.
Article in English | MEDLINE | ID: mdl-38942069

ABSTRACT

The cryopreservation of teleost eggs and embryos remains challenging, and there are no previous reports that demonstrate successful cryopreservation in medaka (Oryzias latipes). We have reported egg and sperm production, followed by the generation of donor-derived offspring by transplanting vitrified whole testes-derived testicular cells into surrogate fish. The vitrification solutions contained ethylene glycol, sucrose, and ficoll. In this study, we replaced sucrose with trehalose in the vitrification solution and medaka whole testis was vitrified with the solution. The post-vitrification survival (72.8±3.5%) was markedly improved compared with that achieved using the sucrose-containing solution (44.7±4.2%). Moreover, we demonstrated the production of eggs, sperm, and donor-derived offspring from testicular cells transplanted into surrogate recipients. The phenotype of donor-derived offspring was identical to that of transplanted testicular cells. These findings suggest that trehalose is effective for the vitrification of medaka whole testis and can be considered an effective and reliable method for the long-term preservation of their genetic resources.

11.
Animals (Basel) ; 14(12)2024 Jun 07.
Article in English | MEDLINE | ID: mdl-38929336

ABSTRACT

Testicular development and spermatogenesis are tightly regulated by both coding and non-coding genes, with mRNA and lncRNA playing crucial roles in post-transcriptional gene expression regulation. However, there are significant differences in regulatory mechanisms before and after sexual maturity. Nevertheless, the mRNAs and lncRNAs in the testes of Mongolian horses have not been systematically identified. In this study, we first identified the testicular tissues of sexually immature and sexually mature Mongolian horses at the tissue and protein levels, and comprehensively analyzed the expression profiles of mRNA and lncRNA in the testes of 1-year-old (12 months, n = 3) and 10-year-old (n = 3) Mongolian horses using RNA sequencing technology. Through gene expression analysis, we identified 16,582 mRNAs and 2128 unknown lncRNAs that are commonly expressed in both sexually immature and sexually mature Mongolian horses. Meanwhile, 9217 mRNAs (p < 0.05) and 2191 unknown lncRNAs (p < 0.05) were identified as differentially expressed between the two stages, which were further validated by real-time fluorescent quantitative PCR and analyzed using Gene Ontology (GO) and the Kyoto Encyclopedia of Genes and Genomes (KEGG). The analysis results showed that genes in the sexually immature stage were mainly enriched in terms related to cellular infrastructure, while genes in the sexually mature stage were enriched in terms associated with hormones, metabolism, and spermatogenesis. In summary, the findings of this study provide valuable resources for a deeper understanding of the molecular mechanisms underlying testicular development and spermatogenesis in Mongolian horses and offer new perspectives for future related research.

12.
Nutrients ; 16(12)2024 Jun 09.
Article in English | MEDLINE | ID: mdl-38931170

ABSTRACT

Androgen production primarily occurs in Leydig cells located in the interstitial compartment of the testis. In aging males, testosterone is crucial for maintaining muscle mass and strength, bone density, sexual function, metabolic health, energy levels, cognitive function, as well as overall well-being. As men age, testosterone production by Leydig cells of the testes begins to decline at a rate of approximately 1% per year starting from their 30s. This review highlights recent findings concerning the use of natural polyphenolics compounds, such as flavonoids, resveratrol, and phenolic acids, to enhance testosterone production, thereby preventing age-related degenerative conditions associated with testosterone insufficiency. Interestingly, most of the natural polyphenolic antioxidants having beneficial effects on testosterone production tend to enhance the expression of the steroidogenic acute regulatory protein (Star) gene in Leydig cells. The STAR protein facilitates the entry of the steroid precursor cholesterol inside mitochondria, a rate-limiting step for androgen biosynthesis. Natural polyphenolic compounds can also improve the activities of steroidogenic enzymes, hypothalamus-pituitary gland axis signaling, and testosterone bioavailability. Thus, many polyphenolic compounds such as luteolin, quercetin, resveratrol, ferulic acid phenethyl ester or gigantol may be promising in delaying the initiation of late-onset hypogonadism accompanying aging in males.


Subject(s)
Antioxidants , Hypogonadism , Polyphenols , Testosterone , Male , Humans , Hypogonadism/drug therapy , Antioxidants/pharmacology , Polyphenols/pharmacology , Testosterone/metabolism , Leydig Cells/drug effects , Leydig Cells/metabolism , Animals , Aging/drug effects , Phosphoproteins/metabolism , Resveratrol/pharmacology
13.
Environ Pollut ; 357: 124393, 2024 Jun 18.
Article in English | MEDLINE | ID: mdl-38901820

ABSTRACT

Biomonitoring studies have shown that pregnant women living in regions of unconventional natural gas (UNG) exploitation have higher levels of trace elements. Whether developmental endocrine disruption can be expected at these exposure levels during pregnancy is unclear. In this study, we aimed to test the impact of five trace elements alone or in mixtures using in vitro cell- and tissue-based assays relevant to endocrine disruption and development. Manganese, aluminum, strontium, barium, and cobalt were tested at concentrations including those representatives of human fetal exposure. Using transactivation assays, none of the tested elements nor their mixture altered the human estrogen receptor 1 or androgen receptor genomic signalling. In the rat fetal testis assay, an organ culture system, cobalt (5 µg/l), barium (500 µg/l) and strontium (500 µg/l) significantly increased testosterone secretion. Cobalt and strontium were associated with hyperplasia and/or hypertrophy of fetal Leydig cells. Mixing the five elements at concentrations where none had an effect individually stimulated testosterone secretion by the rat fetal testis paralleled by the significant increase of 3ß-hydroxysteroid dehydrogenase protein level in comparison to the vehicle control. The mechanisms involved may be specific to the fetal testis as no effect was observed in the steroidogenic H295R cells. Our data suggest that some trace elements in mixture at concentrations representative of human fetal exposure can impact testis development and function. This study highlights the potential risk posed by UNG operations, especially for the most vulnerable populations, pregnant individuals, and their fetus.

14.
World J Urol ; 42(1): 386, 2024 Jun 25.
Article in English | MEDLINE | ID: mdl-38918219

ABSTRACT

BACKGROUND: The last decades revealed new scientific knowledge regarding the fertility and potential malignancy of undescended testis AQ2(UDT). Accordingly, many guidelines changed their recommendation concerning timing of therapy, with the goal of an earlier time of surgery. METHODS: We analyzed the number of new diagnosis and performed surgeries in predefined age groups provided by the obligatory annual reports of German hospitals in the reimbursement.INFO"-tool between 2006 and 2020. RESULTS: Overall, 124,741 cases were analyzed. We showed a slight increase in performed surgeries in the first year by 2% per year with a main increase till 2011, a constant number of surgeries between first and 4th year and a decrease of surgeries between 5 and 14th year of living with a main decrease till 2009 by 3% per year. CONCLUSION: Even if our results illustrate an increasing adaption of the guideline's recommendation, there is still a significant number of patients who receive later treatment. More research about the reasons and circumstances for the latter is needed.


Subject(s)
Cryptorchidism , Orchiopexy , Practice Guidelines as Topic , Cryptorchidism/surgery , Humans , Male , Germany/epidemiology , Child , Adolescent , Child, Preschool , Infant , Time Factors , Young Adult , Adult
15.
Abdom Radiol (NY) ; 2024 Jun 28.
Article in English | MEDLINE | ID: mdl-38940912

ABSTRACT

PURPOSE: To assess the role of 3.0 T Diffusion Tensor Imaging (DTI) and Fiber Tractography (FT) of the testes in the work-up of nonobstructive azoospermia (NOA). METHODS: This prospective study included consecutive NOA men and controls. A 3.0 T scrotal MRI was performed, including DTI. The testicular apparent diffusion coefficient (ADC) and fractional anisotropy (FA) were calculated. FT reconstructions were created. The Kruskal-Wallis test, followed by pairwise comparisons, assessed differences in testicular ADC and FA between NOA histologic phenotypes (group 1: hypospermatogenesis; group 2: maturation arrest; and group 3: Sertoli cell-only syndrome) and normal testes. The Mann-Whitney-U test compared ADC and FA between NOA testes with positive and negative sperm retrieval. Visual assessment of the testicular fiber tracts was performed. Fiber tracts fewer in number, of reduced thickness, disrupted and/or disorganized were considered "abnormal". Chi-square tests and binary logistic regression analysis assessed variations in testicular fiber tracts morphology. RESULTS: Twenty-nine NOA men (mean age: 39 ± 5.93 years) and 20 controls (mean age: 26 ± 5.83 years) were included for analysis. Higher ADC (p < 0.001) and FA (p < 0.001) was observed in NOA testes compared to controls. Differences in FA were found between groups 1 and 3 (0.07 vs 0.10, p = 0.26) and groups 2 and 3 (0.07 vs 0.10, p = 0.03), but not between groups 1 and 2 (p = 0.66). An increase in FA was observed in NOA testes with Sertoli cell-only syndrome compared to hypospermatogenesis and maturation arrest. FA was higher in NOA testes with negative results for the presence of sperm compared to those with positive results (0.09 vs 0.07, p = 0.006). FT showed "abnormal" fiber tracts in NOA testes (p < 0.001). CONCLUSION: 3.0 T DTI and FT provide an insight into deranged spermatogenesis in NOA testes.

16.
Reprod Biol Endocrinol ; 22(1): 75, 2024 Jun 26.
Article in English | MEDLINE | ID: mdl-38926848

ABSTRACT

BACKGROUND: Testis is an immune privileged organ, which prevents the immune response against sperm antigens and inflammation. Testicular cells responsible for immune tolerance are mainly Sertoli cells, which form the blood-testis barrier and produce immunosuppressive factors. Sertoli cells prevent inflammation in the testis and maintain immune tolerance by inhibiting proliferation and inducing lymphocyte apoptosis. It has been shown that 9-cis-retinoic acid (9cRA) blocks ex vivo apoptosis of peripheral blood lymphocytes and promotes the differentiation of Treg cells in the gut. However, the role of retinoid signaling in regulating the immune privilege of the testes remains unknown. OBJECTIVE: The aim of this study was to determine whether 9cRA, acting via the retinoic acid receptors (RAR) and the retinoic X receptors (RXR), controls the immunomodulatory functions of Sertoli cells by influencing the secretion of anti-inflammatory/pro-inflammatory factors, lymphocyte physiology and Treg cell differentiation. METHODS: Experiments were performed using in vitro model of co-cultures of murine Sertoli cells and T lymphocytes. Agonists and antagonists of retinoic acid receptors were used to inhibit/stimulate retinoid signaling in Sertoli cells. RESULTS: Our results have demonstrated that 9cRA inhibits the expression of immunosuppressive genes and enhances the expression of pro-inflammatory factors in Sertoli cells and lymphocytes, increases lymphocyte viability and decreases apoptosis rate. Moreover, we have found that 9cRA blocks lymphocyte apoptosis acting through both RAR and RXR and inhibiting FasL/Fas/Caspase 8 and Bax/Bcl-2/Caspase 9 pathways. Finally, we have shown that 9cRA signaling in Sertoli cells inhibits Treg differentiation. CONCLUSION: Collectively, our results indicate that retinoid signaling negatively regulates immunologically privileged functions of Sertoli cells, crucial for ensuring male fertility. 9cRA inhibits lymphocyte apoptosis, which can be related to the development of autoimmunity, inflammation, and, in consequence, infertility.


Subject(s)
Cell Differentiation , Sertoli Cells , Signal Transduction , T-Lymphocytes, Regulatory , Tretinoin , Male , Animals , Sertoli Cells/metabolism , Sertoli Cells/drug effects , T-Lymphocytes, Regulatory/drug effects , T-Lymphocytes, Regulatory/metabolism , T-Lymphocytes, Regulatory/immunology , Signal Transduction/drug effects , Mice , Tretinoin/pharmacology , Cell Differentiation/drug effects , Alitretinoin/pharmacology , Receptors, Retinoic Acid/metabolism , Apoptosis/drug effects , Coculture Techniques , Mice, Inbred C57BL , Cells, Cultured , Immunomodulation/drug effects
17.
Biomolecules ; 14(6)2024 May 21.
Article in English | MEDLINE | ID: mdl-38927011

ABSTRACT

Normal testicular development ensures the process of spermatogenesis, which is a complex biological process. The sustained high productivity of spermatogenesis throughout life is predominantly attributable to the constant proliferation and differentiation of spermatogonial stem cells (SSCs). The self-renewal and differentiation processes of SSCs are strictly regulated by the SSC niche. Therefore, understanding the developmental pattern of SSCs is crucial for spermatogenesis. The Shaziling pig is a medium-sized indigenous pig breed originating from central China. It is renowned for its superior meat quality and early male sexual maturity. The spermatogenic ability of the boars is of great economic importance to the pig industry. To investigate testicular development, particularly the pattern of SSC development in Shaziling pigs, we used single-cell transcriptomics to identify gene expression patterns in 82,027 individual cells from nine Shaziling pig testes at three key postnatal developmental stages. We generated an unbiased cell developmental atlas of Shaziling pig testicular tissues. We elucidated the complex processes involved in the development of SSCs within their niche in the Shaziling pig. Specifically, we identified potential marker genes and cellular signaling pathways that regulate SSC self-renewal and maintenance. Additionally, we proposed potential novel marker genes for SSCs that could be used for SSC isolation and sorting in Shaziling pigs. Furthermore, by immunofluorescence staining of testicular tissues of different developmental ages using marker proteins (UCHL1 and KIT), the developmental pattern of the spermatogonia of Shaziling pigs was intensively studied. Our research enhances the comprehension of the development of SSCs and provides a valuable reference for breeding Shaziling pigs.


Subject(s)
RNA-Seq , Spermatogonia , Testis , Animals , Male , Swine/genetics , Spermatogonia/metabolism , Spermatogonia/cytology , Testis/metabolism , Testis/cytology , Testis/growth & development , Adult Germline Stem Cells/metabolism , Adult Germline Stem Cells/cytology , Single-Cell Analysis , Cell Differentiation/genetics , Spermatogenesis/genetics , Stem Cells/metabolism , Stem Cells/cytology , Transcriptome/genetics
18.
Cancers (Basel) ; 16(12)2024 Jun 15.
Article in English | MEDLINE | ID: mdl-38927936

ABSTRACT

We aimed to report sexual and reproductive outcomes following post-chemotherapy robot-assisted retroperitoneal unilateral lymph node dissection (PC-rRPLND) for non-seminomatous germ cell tumors (NSGCTs) at a high-volume cancer center. We collected records regarding sexual and reproductive outcomes of patients undergoing unilateral PC-rRPLND for stage II NSGCTs from January 2018 to November 2021. Preoperative and postoperative (at 12 months) ejaculatory function as well as erectile function, based on the International Index of Erectile Function-5 (IIEF-5) and Erection Hardness Score (EHS), were assessed. Only patients with a pre-operative IIEF-5 of ≥22 and EHS of ≥3 were included in this analysis. Overall, 22 patients undergoing unilateral PC-rRPLND met the inclusion criteria. Of these, seven (31.8%) patients presented an andrological disorder of any type after PC-rRPLND. Specifically, retrograde ejaculation was present in three (13.6%) patients and hypospermia was present in one (4.5%) patient. Moreover, three (13.6%) patients yielded erectile dysfunction (IIEF-5 < 22 and/or EHS < 3). Lastly, two (9.1%) succeeded in naturally conceiving a child after PC-rRPLND. Retrograde ejaculation is confirmed to be one of the most common complications of PC-rRPLND. Moreover, a non-negligible number of patients experience erectile dysfunction.

19.
Parasit Vectors ; 17(1): 252, 2024 Jun 10.
Article in English | MEDLINE | ID: mdl-38858789

ABSTRACT

BACKGROUND: Toxoplasma gondii is an intracellular protozoan parasite that is widely distributed in humans and warm-blooded animals. T. gondii chronic infections can cause toxoplasmic encephalopathy, adverse pregnancy, and male reproductive disorders. In male reproduction, the main function of the testis is to provide a stable place for spermatogenesis and immunological protection. The disorders affecting testis tissue encompass abnormalities in the germ cell cycle, spermatogenic retardation, or complete cessation of sperm development. However, the mechanisms of interaction between T. gondii and the reproductive system is unclear. The aims were to study the expression levels of genes related to spermatogenesis, following T. gondii infection, in mouse testicular tissue. METHODS: RNA-seq sequencing was carried out on mouse testicular tissues from mice infected or uninfected with the T. gondii type II Prugniaud (PRU) strain and validated in combination with real-time quantitative PCR and immunofluorescence assays. RESULTS: The results showed that there were 250 significant differentially expressed genes (DEGs) (P < 0.05, |log2fold change| â‰§ 1). Bioinformatics analysis showed that 101 DEGs were annotated to the 1696 gene ontology (GO) term. While there was a higher number of DEGs in the biological process classification as a whole, the GO enrichment revealed a significant presence of DEGs in the cellular component classification. The Arhgap18 and Syne1 genes undergo regulatory changes following T. gondii infection, and both were involved in shaping the cytoskeleton of the blood-testis barrier (BTB). The number of DEGs enriched in the MAPK signaling pathway, the ERK1/2 signaling pathway, and the JNK signaling pathway were significant. The PTGDS gene is located in the Arachidonic acid metabolism pathway, which plays an important role in the formation and maintenance of BTB in the testis. The expression of PTGDS is downregulated subsequent to T. gondii infection, potentially exerting deleterious effects on the integrity of the BTB and the spermatogenic microenvironment within the testes. CONCLUSIONS: Overall, our research provides in-depth insights into how chronic T. gondii infection might affect testicular tissue and potentially impact male fertility. These findings offer a new perspective on the impact of T. gondii infection on the male reproductive system.


Subject(s)
Testis , Toxoplasma , Toxoplasmosis, Animal , Transcriptome , Animals , Male , Mice , Testis/parasitology , Testis/metabolism , Toxoplasma/genetics , Toxoplasmosis, Animal/parasitology , Spermatogenesis/genetics , Gene Expression Profiling , Chronic Disease , Computational Biology
20.
Biol Reprod ; 2024 Jun 13.
Article in English | MEDLINE | ID: mdl-38869910

ABSTRACT

Melatonin is a pineal hormone that regulates testicular activity (i.e. steroidogenesis and spermatogenesis) through two complementary mechanisms, indirect effects exerted via the hypothalamic-adenohypophyseal-axis and direct actions that take place on the different cell populations of the male gonad. The effects of increased age on the testis and the general mechanisms involved in testicular pathology leading to infertility are still only poorly understood. However, there is growing evidence that link testicular aging and idiopathic male infertility to local inflammatory and oxidative stress events. Because literature data strongly indicate that melatonin exhibits anti-inflammatory and anti-oxidant properties, this review focuses on the potential benefits exerted by this indoleamine at testicular level in male reproductive fertility and aging. Taking into account that the effects of melatonin supplementation on testicular function are currently being investigated, the overview covers not only promising prospects but also many questions concerning the future therapeutic value of this indoleamine as an anti-aging drug as well as in the management of cases of male infertility for which there are no medical treatments currently available.

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