Hedgehog(HH)signaling has been researched for decades and Hedgehog has 3 homologs:Sonic Hedgehog(Shh),Indian Hedgehog(Ihh),and Desert Hedgehog(Dhh).Dhh is the one involved in male gonad and germ cell development.The d...Hedgehog(HH)signaling has been researched for decades and Hedgehog has 3 homologs:Sonic Hedgehog(Shh),Indian Hedgehog(Ihh),and Desert Hedgehog(Dhh).Dhh is the one involved in male gonad and germ cell development.The distribution of molecules in Hedgehog signaling in testis indicated that Hedgehog signaling executes important functions during testis development.The patients with Dhh signaling deficiency develop dysgenesis of gonads and hormone production which demands further exploration of gonad HH signaling.Some results proved the indispensable roles of HH signaling in gonad and germ cell development and the interaction with hormones.This review evaluates HH functions in the testis and how HH affects and is affected by hormones and provides novel insights about HH signaling to the readers.展开更多
The aim of this investigation was to determine the optimal storage medium for testicular hypothermic transportation and identify the ideal concentration for the application of the protective agent 5-aminolevulinic aci...The aim of this investigation was to determine the optimal storage medium for testicular hypothermic transportation and identify the ideal concentration for the application of the protective agent 5-aminolevulinic acid(5-ALA).Furthermore,this study aimed to explore the underlying mechanism of the protective effects of 5-ALA.First,we collected and stored mouse testicular fragments in different media,including Hank’s balanced salt solution(HBSS;n=5),Dulbecco’s Modified Eagle Medium/Nutrient Mixture F-12(DMEM/F12;n=5),and alpha-minimum essential medium(αMEM;n=5).Storage of testicular tissue in HBSS preserved the integrity of testicular morphology better than that in the DMEM/F12 group(P<0.05)and theαMEM group(P<0.01).Testicular fragments were subsequently placed in HBSS with various concentrations of 5-ALA(0[control],1 mmol l−1,2 mmol l−1,and 5 mmol l−1)to determine the most effective concentration of 5-ALA.The 2 mmol l−15-ALA group(n=3)presented the highest positive rate of spermatogonial stem cells compared with those in the control,1 mmol l−1,and 5 mmol l−15-ALA groups.Finally,the tissue fragments were preserved in HBSS with control(n=3)and 2 mmol l−15-ALA(n=3)under low-temperature conditions.A comparative analysis was performed against fresh testes(n=3)to elucidate the underlying mechanism of 5-ALA.Gene set enrichment analysis(GSEA)for WikiPathways revealed that the p38 mitogen-activated protein kinase(MAPK)signaling pathway was downregulated in the 2 mmol l−15-ALA group compared with that in the control group(normalized enrichment score[NES]=−1.57,false discovery rate[FDR]=0.229,and P=0.019).In conclusion,these data suggest that using 2 mmol l−15-ALA in HBSS effectively protected the viability of spermatogonial stem cells upon hypothermic transportation.展开更多
Dear Editor,We are much obliged that Hadziselimovic1 has used our data2 to highlight the substantial proportion of boys with cryptorchidism where gonadotropin insufficiency is an important factor related to the pathog...Dear Editor,We are much obliged that Hadziselimovic1 has used our data2 to highlight the substantial proportion of boys with cryptorchidism where gonadotropin insufficiency is an important factor related to the pathogenesis.We have recently presented a study on a series of 453 consecutive boys with bilateral nonsyndromic cryptorchidism,in which we conducted hormonal evaluations and assessed germ cell numbers in testicular biopsies.3 In this series,45%of the boys were classified as having gonadotropin insufficiency.3 Identifying these patients at the time of surgery is important.A recent follow-up study of 208 boys with nonsyndromic bilateral cryptorchidism from our department showed that the boys with gonadotropin insufficiency had an impaired fertility potential after surgery compared to boys with an intact hypothalamus–pituitary–gonadal feedback mechanism.4 In a review from 2022,Hadziselimovic5 suggested that infertility in patients diagnosed with cryptorchid testes is a consequence of a hormonal deficiency rather than temperature-induced cellular damage.展开更多
Dear Editor,I would like to congratulate Mamsen et al.i on their extensive and scientifically valuable work.I analyzed their raw data presented in Table 1 of the original article from a different perspective and disco...Dear Editor,I would like to congratulate Mamsen et al.i on their extensive and scientifically valuable work.I analyzed their raw data presented in Table 1 of the original article from a different perspective and discovered an effect not mentioned in the article.My analysis showed that luteinizing hormone(LH)levels are significantly lower in patients at high infertility risk(HIR),whose testes lack A dark(Ad)spermatogonia and display an abnormal ratio of germ cells per crosssectional tubule(G/T).展开更多
This study assessed the feasibility of testis tissue cryopreservation (TTC) for fertility preservation in prepubescent boys with cryptorchidism. From January 2014 to December 2022, the University Hospital of Copenhage...This study assessed the feasibility of testis tissue cryopreservation (TTC) for fertility preservation in prepubescent boys with cryptorchidism. From January 2014 to December 2022, the University Hospital of Copenhagen (Rigshospitalet, Copenhagen, Denmark) implemented TTC for 56 boys with cryptorchidism to preserve their reproductive potential. Testis tissue samples were collected during orchiopexy (32 cases) or at subsequent follow-up procedures (24 cases), necessitated by an increased risk of infertility as indicated by hormonal assessments and/or findings from initial surgical biopsies. Testis samples were procured for TTC and pathological analysis. The cohort had an average age of 1.3 (range: 0.3–3.8) years at the time of orchiopexy, with 91.1% presenting bilateral cryptorchidism. The study revealed a median germ cell count of 0.39 (range: 0–2.88) per seminiferous tubule, with germ cells detected in 98.0% of the bilateral biopsies and 100% of the unilateral, indicating a substantial potential for fertility in these immature tissues. A dark spermatogonia (Ad) was detected in 37 out of 56 patients evaluated, with a median Ad spermatogonia count of 0.027 (range: 0.002–0.158) per seminiferous tubule. A total of 30.2% of the samples lacked Ad spermatogonia, indicative of potential gonadotrophin insufficiency. The median hormone levels measured were as follows: follicle-stimulating hormone (FSH) at 0.69 (range: 0.16–2.5) U l−1, luteinizing hormone (LH) at 0.21 (range: 0.05–3.86) U l−1, and inhibin B at 126 (range: 17–300) pg ml−1. Despite early orchiopexy, 20%–25% of boys with cryptorchidism remain at risk for future infertility, substantiating the necessity of TTC as a precaution. The study highlights the need for refined predictive techniques to identify boys at higher risk of future infertility.展开更多
The mechanisms underlying sex determination and differentiation have long intrigued researchers in the fields of development and evolutionary biology.The roughskin sculpin(Trachidermus fasciatus Heckel),displaying sex...The mechanisms underlying sex determination and differentiation have long intrigued researchers in the fields of development and evolutionary biology.The roughskin sculpin(Trachidermus fasciatus Heckel),displaying sexual dimorphism,provides an ideal model for studying the mechanisms.However,both genetic and genomic information concerning sex determination and differentiation,such as gonadal transcriptome data in roughskin sculpin,are lacking.Here,we present the first gonadal transcriptomes of roughskin sculpin and identify sex-related genes.We identified 8531 differentially expressed genes(DEGs),among them 4065 were upregulated in the ovary and 4466 upregulated in the testis.Several sex-related gene ontology(GO)terms were enriched in ovary-biased genes,including“binding of sperm to zona pellucida”,“egg coat formation”,“positive regulation of acrosome reaction”,“cell division”,and“cell cycle”,while the GO terms such as“spermatogenesis”,“sperm axoneme assembly”,“cilium assembly”,“cilium movement”,and“cilium movement involved in cell motility”were enriched in testis-biased genes.Moreover,six KEGG pathways were significantly enriched in the ovary,whereas only one was enriched in the testis.Of these DEGs,40 sex-related genes were identified,which including 26 testis-biased genes(such as Dmrtb 1,Gsdf,Sox 9 b,Wnt 4 b,Tcp 11 l 2,and Efhb),and 14 ovary-biased genes(such as Cyp 19 a 1 a,Foxh 1,Foxr 1,Gdf 3,Hsd 17 b 12,and Igf 2 bp 3).This gonadal transcript dataset would broaden our understanding of sex determination and differentiation mechanisms in roughskin sculpin,expand the genomic database,support future studies on sex-related gene functions,and facilitate molecular biology research into roughskin sculpin.展开更多
Central precocious puberty secondary to Leydig cell tumors is rare in children. We retrospectively analyzed the mid- to long-term follow-up data of patients with Leydig cell tumors. The clinical data of 12 consecutive...Central precocious puberty secondary to Leydig cell tumors is rare in children. We retrospectively analyzed the mid- to long-term follow-up data of patients with Leydig cell tumors. The clinical data of 12 consecutive patients who were treated at Beijing Children’s Hospital, Capital Medical University (Beijing, China), between January 2016 and October 2023 were retrospectively reviewed. Clinical evaluations, including physical examination, hormone examination, serum tumor marker analysis, abdominal and scrotal ultrasound, chest X-ray, and bone age measurement, were conducted before surgery and at follow-up time points. Surgical approaches were selected according to the individual conditions. Patients with an abnormal hormonal status and suspected of having central precocious puberty were referred to endocrinologists to confirm the diagnosis. Subsequently, gonadotropin-releasing hormone analog therapy was proposed. The mean patient age was 81.3 (range: 40–140) months at the time of the operation. Ten patients had peripheral precocious puberty at admission. All patients had elevated preoperative testosterone levels, whereas tumor marker levels were normal. Testis-sparing surgery was performed in eleven patients, and radical orchiectomy was performed in one patient. The follow-up duration (mean ± standard deviation) was 36.2 ± 25.3 months. Five patients had central precocious puberty, with a mean duration of 3.4 (range: 1–6) months postoperatively. Three patients were receiving gonadotropin-releasing hormone analog therapy, and good suppression of puberty was observed. No risk factors were found for secondary central precocious puberty. There was a high prevalence of central precocious puberty secondary to Leydig cell tumors in our study. Gonadotropin-releasing hormone analog therapy has satisfactory treatment effects. Larger sample sizes and long-term follow-up are needed in future studies.展开更多
Polyorchidism is a rare anomaly of the male urogenital tract characterized by the presence of one or more extra testes.Supernumerary testes can often present with coexistent conditions,including cryptorchidism,inguina...Polyorchidism is a rare anomaly of the male urogenital tract characterized by the presence of one or more extra testes.Supernumerary testes can often present with coexistent conditions,including cryptorchidism,inguinal hernia,and torsion.We report a case of a pediatric patient with initial concern for intra-scrotal left testicular torsion on ultrasonography who was ultimately found to have torsion of an intra-abdominal supernumerary testis.He underwent scrotal exploration with bilateral orchiopexy and laparoscopic excision of the torsed gonad.This case highlights a unique presentation of polyorchidism with incongruent descent of an ipsilateral supernumerary testis.展开更多
Testicular descent occurs in two consecutive stages:the transabdominal stage and the inguinoscrotal stage.Androgens play a crucial role in the second stage by influencing the development of the gubernaculum,a structur...Testicular descent occurs in two consecutive stages:the transabdominal stage and the inguinoscrotal stage.Androgens play a crucial role in the second stage by influencing the development of the gubernaculum,a structure that pulls the testis into the scrotum.However,the mechanisms of androgen actions underlying many of the processes associated with gubernaculum development have not been fully elucidated.To identify the androgen-regulated genes,we conducted large-scale gene expression analyses on the gubernaculum harvested from luteinizing hormone/choriogonadotropin receptor knockout(Lhcgr KO)mice,an animal model of inguinoscrotal testis maldescent resulting from androgen deficiency.We found that the expression of secreted protein acidic and rich in cysteine(SPARC)-related modular calcium binding 1(Smoc1)was the most severely suppressed at both the transcript and protein levels,while its expression was the most dramatically induced by testosterone administration in the gubernacula of Lhcgr KO mice.The upregulation of Smoc1 expression by testosterone was curtailed by the addition of an androgen receptor antagonist,flutamide.In addition,in vitro studies demonstrated that SMOC1 modestly but significantly promoted the proliferation of gubernacular cells.In the cultures of myogenic differentiation medium,both testosterone and SMOC1 enhanced the expression of myogenic regulatory factors such as paired box 7(Pax7)and myogenic factor 5(Myf5).After short-interfering RNA-mediated knocking down of Smoc1,the expression of Pax7 and Myf5 diminished,and testosterone alone did not recover,but additional SMOC1 did.These observations indicate that SMOC1 is pivotal in mediating androgen action to regulate gubernaculum development during inguinoscrotal testicular descent.展开更多
To investigate the impact of preoperative serum follicle-stimulating hormone(FSH)levels on the probability of testicular sperm retrieval,we conducted a study of nonobstructive azoospermic(NOA)men with different testic...To investigate the impact of preoperative serum follicle-stimulating hormone(FSH)levels on the probability of testicular sperm retrieval,we conducted a study of nonobstructive azoospermic(NOA)men with different testicular volumes(TVs)who underwent microdissection testicular sperm extraction(micro-TESE).A total of 177 NOA patients undergoing micro-TESE for the first time from April 2019 to November 2022 in Shenzhen Zhongshan Obstetrics and Gynecology Hospital(formerly Shenzhen Zhongshan Urology Hospital,Shenzhen,China)were retrospectively reviewed.The subjects were divided into four groups based on average TV quartiles.Serum hormone levels in each TV group were compared between positive and negative sperm retrieval subgroups.Overall sperm retrieval rate was 57.6%.FSH levels(median[interquartile range])were higher in the positive sperm retrieval subgroup compared with the negative outcome subgroup when average TV was<5 ml(first quartile[Q1:TV<3 ml]:43.32[17.92]IU l^(−1) vs 32.95[18.56]IU l−1,P=0.048;second quartile[Q2:3 ml≤TV<5 ml]:31.31[15.37]IU l^(−1) vs 25.59[18.40]IU l^(−1),P=0.042).Elevated serum FSH levels were associated with successful micro-TESE sperm retrieval in NOA men whose average TVs were<5 ml(adjusted odds ratio[OR]:1.06 per unit increase;95%confidence interval[CI]:1.01–1.11;P=0.011).In men with TVs≥5 ml,larger TVs were associated with lower odds of sperm retrieval(adjusted OR:0.84 per 1 ml increase;95%CI:0.71–0.98;P=0.029).In conclusion,elevated serum FSH levels were associated with positive sperm retrieval in micro-TESE in NOA men with TVs<5 ml.In men with TV≥5 ml,increases in average TVs were associated with lower odds of sperm retrieval.展开更多
Objective To investigate the value of the clinical application of fetal testis transplantation with main vessel segment. Methods The testicular transplantation were performed to cure 9 patients suffered from male hypo...Objective To investigate the value of the clinical application of fetal testis transplantation with main vessel segment. Methods The testicular transplantation were performed to cure 9 patients suffered from male hyponadism with the fetal testis with main vessel segment as donor tissue. Results Except one, 8 patients had a significantly increased level of serum testosterone, the male secondary sexual characteristics and the sexual desire were improved. The size of testis was larger than before operation. Conclusion Fetal testis transplantation with main vessel segment is a effective method of cure male hyponadism and has great value of clinical application. 2 refs.展开更多
Aim： To investigate the distribution of cation channel of sperm 1 （CATSPER1） protein and the presence of CATSPER1 mRNA in human testis and ejaculated spermatozoa. The influence of anti-human CATSPER1 antibody upon ...Aim： To investigate the distribution of cation channel of sperm 1 （CATSPER1） protein and the presence of CATSPER1 mRNA in human testis and ejaculated spermatozoa. The influence of anti-human CATSPER1 antibody upon human sperm motility was used to evaluate the function of human CATSPER1 and to estimate its possible use as a target for immunocontraception. Methods： Human ejaculated sperm from normozoospermic donors （n = 12） and liquid nitrogen frozen human testis were used for the study of mRNA and protein expression of CATSPER1 by reverse transcription polymerase chain reaction （RT-PCR） and immunohistochemistry, respectively. Spermatozoa from normozoospermic donors （n = 12） were individually processed using a swim-up procedure and were then incubated with CATSPER1 antibody at final concentrations of 20, 4 and 0.8 μg/mL. After 1, 2 and 6 h incubation, progressive motility and fast progressive motility were measured by means of computer-assisted semen analysis. Results： CATSPER1 transcript was detected in both human testis and each human ejaculated semen sample. CATSPER1 protein expressed in the membrane of spermatid and was localized in the principal piece of the sperm tail. The application of CATSPER1 antibody at all concentrations significantly inhibited both progressive motility and fast progressive motility after 1, 2 and 6 h incubation, and significant dose-dependent changes were observed. Conclusion： CATSPER1 is meiotically and post-meiotically expressed in human testis tissue. CATSPER1 mRNA in human ejaculated spermatozoa could be a more feasible target for study and infertility screening than testis biopsy. In addition, our results suggest that human CATSPER1 could be a possible target for immunocontraception.展开更多
Aim： To examine the effects of melatonin treatment on lipid peroxidation （LPO） and the activities of antioxidant enzymes in the testicular tissue of streptozotocin （STZ）-induced diabetic rats. Methods： Twenty-si...Aim： To examine the effects of melatonin treatment on lipid peroxidation （LPO） and the activities of antioxidant enzymes in the testicular tissue of streptozotocin （STZ）-induced diabetic rats. Methods： Twenty-six male rats were randomly divided into three groups as follows： group Ⅰ, control, non-diabetic rats （n = 9）; group Ⅱ, STZ-induced, untreated diabetic rats （n = 8）; group Ⅲ, STZ-induced, melatonin-treated （dose of 10 mg/kg·day） diabetic rats （n = 9）. Following 8-week melatonin treatment, all rats were anaesthetized and then were killed to remove testes from the scrotum. Results： As compared to group Ⅰ, in rat testicular tissues of grouap Ⅱ, increased levels of malondialdehyde （MDA） （P 〈 0.01） and superoxide dismutase （SOD） （P 〈 0.01） as well as, decreased levels of catalase （CAT） （P 〈 0.01） and glutathione peroxidase （GSH-Px） （P 〉 0.05） were found. In contrast, as compared to group Ⅱ, in rat testicular tissues of group Ⅲ, levels of MDA decreased （but this decrease was not significant, P 〉 0.05） and SOD （P 〈 0.01） as well as CAT （P 〈 0.05） increased. GSH-Px was not influenced by any of the treatment. Melatonin did not significantly affect the elevated glucose concentration of diabetic group. At the end of the study, there was no significant difference between the melatonin-treated group and the untreated group by means of body and testicular weight. Conclusion： Diabetes mellitus increases oxidative stress and melatonin inhibits lipid peroxidation and might regulate the activities of antioxidant enzymes of diabetic rat testes.展开更多
<abstract>Aim: To study the expression and regulation of Smadl, Smad2 and Smad4 proteins (intracellular signaling molecules of transforming growth factor-β family) in rat testis during postnatal development. Me...<abstract>Aim: To study the expression and regulation of Smadl, Smad2 and Smad4 proteins (intracellular signaling molecules of transforming growth factor-β family) in rat testis during postnatal development. Methods: The whole testes were collected from SD rats aged 3, 7, 14, 28 and 90 (adult) days. The cellular localization and developmental changes were examined by immunohistochemistry ABC method with the glucose oxidase-DAB-nickel enhancement technique. Quantitative analysis of the immunostaining was made by the image analysis system. The Smads proteins coexistence in the adult rat testis was tested by the double immune staining for CD14-Smad4 and Smad2-Smad4. The protein expression of Smad during rat testicular development was examined by means of Western blots. Results: Smadl, Smad2 and Smad4 were present throughout testicular development. The immunostaining of Smadl and Smad2 were present in spermatogenic cells. A positive immunoreactivity was located at the cytoplasm, but the nucleus was negative. Smadl was immunolocalized at the d14, d28 and adult testes, while Smad2, at the d7, d14, d28 and adult testis. There was positive irnmunoreaction in the Sertoli cells and Leydig cells as well. The immunolocalization of Smad4 was exclusively at the cytoplasm of Leydig cells and the nuclei were negative throughout the testicular development. No expression was detected in the germ cells. The results of image and statistical analysis showed that generally the expression of Smadl, Smad2 and Smad4 in the testis tended to increase gradually with the growth of the rat. Conclusion: The present data provide direct evidences for the molecular mechanism of TGF-βaction in rat testes during postnatal development and spermatogenesis.展开更多
Aim： To quantitatively study the histological changes of the testis and epididymis as a result of a drastic reduction of testosterone secretion. Methods： Fourteen adult Sprague-Dawley rats were injected intraperiton...Aim： To quantitatively study the histological changes of the testis and epididymis as a result of a drastic reduction of testosterone secretion. Methods： Fourteen adult Sprague-Dawley rats were injected intraperitoneally with ethane dimethane sulfonate （EDS, 75 mg/kg） and the same number of animals were injected with normal saline as a control. At days 7 and 12 （after treatment）, respectively, half of the animals from each group were killed. The testes and epididymides were removed and tissue blocks embedded in methacrylate resin. The cell number per testis was estimated using the stereological optical disector and some other parameters were obtained using other morphometric methods. Results： The EDS treatment resulted in an almost complete elimination of Leydig cells but had no effect on the numbers of Sertoli cells per testis. At day 7 after EDS treatment, many elongated spermatids were retained in the seminiferous epithelium and many round spermatids could be seen in the epididymal ducts. At day 12, a looser arrangement of spermatids and spermatocytes became evident, with apparent narrow empty spaces being formed between germ cells in an approximately radial direction towards the tubule lumen; the numbers （per testis） of non-type B spermatogonia and spermatocytes were similar to controls, whereas that of type B spermatogonia increased by 59%, and that of early round, elongating and late elongated spermatids decreased by 37%, 72% and 52%, respectively. Conclusion： The primary spermatogenic lesions following EDS administration were （i） spermiation failure and （ii） detachment of spermatids and spermatocytes associated with impairment in spermiogenesis and meiosis.展开更多
For centuries, plants and plant-based products have been used as a valuable and safe natural source of medicines for treating various ailments. The therapeutic potential of most of these plants could be ascribed to th...For centuries, plants and plant-based products have been used as a valuable and safe natural source of medicines for treating various ailments. The therapeutic potential of most of these plants could be ascribed to their anticancer, antidiabetic, hepatoprotective, cardioprotective, antispasmodic, analgesic and various other pharmacological properties. However, several commonly used plants have been reported to adversely affect male reproductive functions in wildlife and humans. The effects observed with most of the plant and plant-based products have been attributed to the antispermatogenic and/or antisteroidogenic properties of one or more active ingredients. This review discusses the detrimental effects of some of the commonly used plants on various target cells in the testis. A deeper insight into the molecular mechanisms of action of these natural compounds could pave the way for developing therapeutic strategies against their toxicity.展开更多
Colorectal cancer ranks third among the estimatedcancer cases and cancer related mortalities in United States in 2014. Early detection and efficient therapy remains a significant clinical challenge for this disease. T...Colorectal cancer ranks third among the estimatedcancer cases and cancer related mortalities in United States in 2014. Early detection and efficient therapy remains a significant clinical challenge for this disease. Therefore, there is a need to identify novel tumor asso-ciated molecules to target for biomarker development and immunotherapy. In this regard, cancer testis antigens have emerged as a potential targets for developing novel clinical biomarkers and immunotherapy for various malignancies. These germ cell specific proteins exhibit aberrant expression in cancer cells and contribute in tumorigenesis. Owing to their unique expression profile and immunogenicity in cancer patients, cancer testis antigens are clinically referred as the most promising tumor associated antigens. Several cancer testis antigens have been studied in colorectal cancer but none of them could be used in clinical practice. This review is an attempt to address the promising cancer testis antigens in colorectal cancer and their possible clinical implications as biomarkers and immunotherapeutic targets with particular focus on challenges and future interventions.展开更多
Successful spermatogonial transplantation requires depletion of the host germ cells to allow efficient colonization of the donor spermatogonial stem cells. Although a sterilizing drug,busulfan （Myleran）,is commonly ...Successful spermatogonial transplantation requires depletion of the host germ cells to allow efficient colonization of the donor spermatogonial stem cells. Although a sterilizing drug,busulfan （Myleran）,is commonly used for preparing a recipient mouse before transplantation,the optimal dose of this drug has not yet been defined.The present study investigated the effects of different doses of busulfan （10-50 mg per kg body weight） on survival rate,testicular mass and histomorphology,and on the haploid spermatids and spermatozoa of male BALB/c mice.The results suggest that a dosage of 30 mg kg^-1 is optimal for the ablative treatment withbusulfan used to prepare the recipient mice. This dose results in an adequate depletion of the host germ cells for colonization of donorderived spermatogonial stem cells and causes the lowest death rate of the animals.展开更多
Aim:To identify and characterize a novel gene with potential roles in testis development and spermatogenesis. Methods:A cDNA microarray was constructed from a human testis large insert cDNA library and hybridized with...Aim:To identify and characterize a novel gene with potential roles in testis development and spermatogenesis. Methods:A cDNA microarray was constructed from a human testis large insert cDNA library and hybridized with probes of human or mouse adult and fetal testes.Differentially expressed genes were isolated and sequenced.RT-PCR was used to test the tissue distribution of the genes of interest and in situ hybridization was performed to localize the gene expression in the mouse testis.A range of bioinformatical programs including Gene Runner,SMART,NCBI Blast and Emboss CpGPlot were used to characterize the new gene's feature.Results:A novel testis-specific gene, NYD-SP5,was differentially expressed in fetal and adult testes.The deduced protein structure of NYD-SP5 was found to contain an IQ motif (a short calmodulin-binding motif containing conserved lie and Gin residues),a Carbam- ate kinase-like domain,a Zn-dependent exopeptidase domain and a lactate dehydrogenase (LDH) C-terminal-like domain.RT-PCR analysis revealed that NYD-SP5 was predominantly expressed in the testis but not in other 15 tissues examined.In situ hybridization and RT-PCR examinations revealed that the expression of NYD-SP5 was confined in the male germ cell but not present in the somatic cell in the testes.Conclusion:NYD-SP5 is a newly found testis- specific gene with potential roles in testis development and spermatogenesis through a calmodulin-activated enzyme.展开更多
Aim: To evaluate the effect of oxidative stress on the spermatogenesis and lactate dehydrogenase-X (LDH-X) activity in mouse testis. Methods: For creating different levels of oxidative stress in mice, three selenium (...Aim: To evaluate the effect of oxidative stress on the spermatogenesis and lactate dehydrogenase-X (LDH-X) activity in mouse testis. Methods: For creating different levels of oxidative stress in mice, three selenium (Se) level diets were fed in separate groups for 8 weeks. Group 1 animals were fed yeast-based Se-deficient (0.02 ppm) diet. Group 2 and Group 3 animals were fed with the same diet supplemented with 0.2 ppm and 1 ppm Se as sodium selenite, respectively. After 8 weeks, biochemical and histopathological observations of the testis were carried out. LDH-X levels in the testis were analyzed by western immunoblot and ELISA. Results: A significant decrease in testis Se level was observed in Group 1 animals, whereas it was enhanced in Group 3 as compared to Group 2. The glutathione peroxidase (GSH-Px) activity was significantly reduced in both the liver and testis in Group 1, but not in Group 2 and 3. A significant increase in the testis glutathione-S-transferase (GST) activity was observed in Group 1, whereas no significant change was seen in Groups 2 and 3. Histological analysis of testis revealed a normal structure in Group 2. A significant decrease in the germ cell population in Group 1 was observed as compared to Group 2 with the spermatids and mature sperm affected the most. Decrease in the lumen size was also observed. In the Se-excess group (Group 3), displacement of germ cell population was observed. Further, a decrease in the LDH-X level in testis was observed in Group 1. Conclusion: Excessive oxidative stress in the Se deficient group, as indicated by changes in the GSH-Px/GST activity, affects the spermatogenic process with a reduction in mature sperm and in turn the LDH-X level.展开更多
基金supported in part by the National Natural Science Foundation of China(Nos.32270555 and 32072954).
文摘Hedgehog(HH)signaling has been researched for decades and Hedgehog has 3 homologs:Sonic Hedgehog(Shh),Indian Hedgehog(Ihh),and Desert Hedgehog(Dhh).Dhh is the one involved in male gonad and germ cell development.The distribution of molecules in Hedgehog signaling in testis indicated that Hedgehog signaling executes important functions during testis development.The patients with Dhh signaling deficiency develop dysgenesis of gonads and hormone production which demands further exploration of gonad HH signaling.Some results proved the indispensable roles of HH signaling in gonad and germ cell development and the interaction with hormones.This review evaluates HH functions in the testis and how HH affects and is affected by hormones and provides novel insights about HH signaling to the readers.
基金funded by the National Natural Science Foundation of China(No.81971759 and No.82171604)the Guangdong Basic and Applied Basic Research Foundation(2023B1515020108)+3 种基金the Science and Technology Program of Guangzhou(202206010089)the Excellent Talents Training Project of The Sixth Affiliated Hospital of Sun Yat-sen University(R20210217202601970)the Postdoctoral Fellowship Program of CPSF(GZC20233216)the Basic and Applied Basic Research Foundation of Guangdong Province(2021A1515111195).
文摘The aim of this investigation was to determine the optimal storage medium for testicular hypothermic transportation and identify the ideal concentration for the application of the protective agent 5-aminolevulinic acid(5-ALA).Furthermore,this study aimed to explore the underlying mechanism of the protective effects of 5-ALA.First,we collected and stored mouse testicular fragments in different media,including Hank’s balanced salt solution(HBSS;n=5),Dulbecco’s Modified Eagle Medium/Nutrient Mixture F-12(DMEM/F12;n=5),and alpha-minimum essential medium(αMEM;n=5).Storage of testicular tissue in HBSS preserved the integrity of testicular morphology better than that in the DMEM/F12 group(P<0.05)and theαMEM group(P<0.01).Testicular fragments were subsequently placed in HBSS with various concentrations of 5-ALA(0[control],1 mmol l−1,2 mmol l−1,and 5 mmol l−1)to determine the most effective concentration of 5-ALA.The 2 mmol l−15-ALA group(n=3)presented the highest positive rate of spermatogonial stem cells compared with those in the control,1 mmol l−1,and 5 mmol l−15-ALA groups.Finally,the tissue fragments were preserved in HBSS with control(n=3)and 2 mmol l−15-ALA(n=3)under low-temperature conditions.A comparative analysis was performed against fresh testes(n=3)to elucidate the underlying mechanism of 5-ALA.Gene set enrichment analysis(GSEA)for WikiPathways revealed that the p38 mitogen-activated protein kinase(MAPK)signaling pathway was downregulated in the 2 mmol l−15-ALA group compared with that in the control group(normalized enrichment score[NES]=−1.57,false discovery rate[FDR]=0.229,and P=0.019).In conclusion,these data suggest that using 2 mmol l−15-ALA in HBSS effectively protected the viability of spermatogonial stem cells upon hypothermic transportation.
文摘Dear Editor,We are much obliged that Hadziselimovic1 has used our data2 to highlight the substantial proportion of boys with cryptorchidism where gonadotropin insufficiency is an important factor related to the pathogenesis.We have recently presented a study on a series of 453 consecutive boys with bilateral nonsyndromic cryptorchidism,in which we conducted hormonal evaluations and assessed germ cell numbers in testicular biopsies.3 In this series,45%of the boys were classified as having gonadotropin insufficiency.3 Identifying these patients at the time of surgery is important.A recent follow-up study of 208 boys with nonsyndromic bilateral cryptorchidism from our department showed that the boys with gonadotropin insufficiency had an impaired fertility potential after surgery compared to boys with an intact hypothalamus–pituitary–gonadal feedback mechanism.4 In a review from 2022,Hadziselimovic5 suggested that infertility in patients diagnosed with cryptorchid testes is a consequence of a hormonal deficiency rather than temperature-induced cellular damage.
文摘Dear Editor,I would like to congratulate Mamsen et al.i on their extensive and scientifically valuable work.I analyzed their raw data presented in Table 1 of the original article from a different perspective and discovered an effect not mentioned in the article.My analysis showed that luteinizing hormone(LH)levels are significantly lower in patients at high infertility risk(HIR),whose testes lack A dark(Ad)spermatogonia and display an abnormal ratio of germ cells per crosssectional tubule(G/T).
基金financially supported by the University Hospital of Copenhagen,Rigshospitalet,the Danish Child Cancer Foundation(2021-7395)Vissing Fonden(519140 AHO/PPT)the Research Fund between Rigshospitalet and Odense University Hospital(136-A5544).
文摘This study assessed the feasibility of testis tissue cryopreservation (TTC) for fertility preservation in prepubescent boys with cryptorchidism. From January 2014 to December 2022, the University Hospital of Copenhagen (Rigshospitalet, Copenhagen, Denmark) implemented TTC for 56 boys with cryptorchidism to preserve their reproductive potential. Testis tissue samples were collected during orchiopexy (32 cases) or at subsequent follow-up procedures (24 cases), necessitated by an increased risk of infertility as indicated by hormonal assessments and/or findings from initial surgical biopsies. Testis samples were procured for TTC and pathological analysis. The cohort had an average age of 1.3 (range: 0.3–3.8) years at the time of orchiopexy, with 91.1% presenting bilateral cryptorchidism. The study revealed a median germ cell count of 0.39 (range: 0–2.88) per seminiferous tubule, with germ cells detected in 98.0% of the bilateral biopsies and 100% of the unilateral, indicating a substantial potential for fertility in these immature tissues. A dark spermatogonia (Ad) was detected in 37 out of 56 patients evaluated, with a median Ad spermatogonia count of 0.027 (range: 0.002–0.158) per seminiferous tubule. A total of 30.2% of the samples lacked Ad spermatogonia, indicative of potential gonadotrophin insufficiency. The median hormone levels measured were as follows: follicle-stimulating hormone (FSH) at 0.69 (range: 0.16–2.5) U l−1, luteinizing hormone (LH) at 0.21 (range: 0.05–3.86) U l−1, and inhibin B at 126 (range: 17–300) pg ml−1. Despite early orchiopexy, 20%–25% of boys with cryptorchidism remain at risk for future infertility, substantiating the necessity of TTC as a precaution. The study highlights the need for refined predictive techniques to identify boys at higher risk of future infertility.
基金Supported by the National Natural Science Foundation of China(Nos.31972793,31502169)the Key Scientific Research Project in Universities and Colleges in Tianjin(No.2022ZD004)。
文摘The mechanisms underlying sex determination and differentiation have long intrigued researchers in the fields of development and evolutionary biology.The roughskin sculpin(Trachidermus fasciatus Heckel),displaying sexual dimorphism,provides an ideal model for studying the mechanisms.However,both genetic and genomic information concerning sex determination and differentiation,such as gonadal transcriptome data in roughskin sculpin,are lacking.Here,we present the first gonadal transcriptomes of roughskin sculpin and identify sex-related genes.We identified 8531 differentially expressed genes(DEGs),among them 4065 were upregulated in the ovary and 4466 upregulated in the testis.Several sex-related gene ontology(GO)terms were enriched in ovary-biased genes,including“binding of sperm to zona pellucida”,“egg coat formation”,“positive regulation of acrosome reaction”,“cell division”,and“cell cycle”,while the GO terms such as“spermatogenesis”,“sperm axoneme assembly”,“cilium assembly”,“cilium movement”,and“cilium movement involved in cell motility”were enriched in testis-biased genes.Moreover,six KEGG pathways were significantly enriched in the ovary,whereas only one was enriched in the testis.Of these DEGs,40 sex-related genes were identified,which including 26 testis-biased genes(such as Dmrtb 1,Gsdf,Sox 9 b,Wnt 4 b,Tcp 11 l 2,and Efhb),and 14 ovary-biased genes(such as Cyp 19 a 1 a,Foxh 1,Foxr 1,Gdf 3,Hsd 17 b 12,and Igf 2 bp 3).This gonadal transcript dataset would broaden our understanding of sex determination and differentiation mechanisms in roughskin sculpin,expand the genomic database,support future studies on sex-related gene functions,and facilitate molecular biology research into roughskin sculpin.
文摘Central precocious puberty secondary to Leydig cell tumors is rare in children. We retrospectively analyzed the mid- to long-term follow-up data of patients with Leydig cell tumors. The clinical data of 12 consecutive patients who were treated at Beijing Children’s Hospital, Capital Medical University (Beijing, China), between January 2016 and October 2023 were retrospectively reviewed. Clinical evaluations, including physical examination, hormone examination, serum tumor marker analysis, abdominal and scrotal ultrasound, chest X-ray, and bone age measurement, were conducted before surgery and at follow-up time points. Surgical approaches were selected according to the individual conditions. Patients with an abnormal hormonal status and suspected of having central precocious puberty were referred to endocrinologists to confirm the diagnosis. Subsequently, gonadotropin-releasing hormone analog therapy was proposed. The mean patient age was 81.3 (range: 40–140) months at the time of the operation. Ten patients had peripheral precocious puberty at admission. All patients had elevated preoperative testosterone levels, whereas tumor marker levels were normal. Testis-sparing surgery was performed in eleven patients, and radical orchiectomy was performed in one patient. The follow-up duration (mean ± standard deviation) was 36.2 ± 25.3 months. Five patients had central precocious puberty, with a mean duration of 3.4 (range: 1–6) months postoperatively. Three patients were receiving gonadotropin-releasing hormone analog therapy, and good suppression of puberty was observed. No risk factors were found for secondary central precocious puberty. There was a high prevalence of central precocious puberty secondary to Leydig cell tumors in our study. Gonadotropin-releasing hormone analog therapy has satisfactory treatment effects. Larger sample sizes and long-term follow-up are needed in future studies.
文摘Polyorchidism is a rare anomaly of the male urogenital tract characterized by the presence of one or more extra testes.Supernumerary testes can often present with coexistent conditions,including cryptorchidism,inguinal hernia,and torsion.We report a case of a pediatric patient with initial concern for intra-scrotal left testicular torsion on ultrasonography who was ultimately found to have torsion of an intra-abdominal supernumerary testis.He underwent scrotal exploration with bilateral orchiopexy and laparoscopic excision of the torsed gonad.This case highlights a unique presentation of polyorchidism with incongruent descent of an ipsilateral supernumerary testis.
基金supported in part by the Department of OB/GYN research funds(University of Louisville,Louisville,KY,USA)Jilin Province Health Technology Capability Enhancement funds(No.2022JC055).
文摘Testicular descent occurs in two consecutive stages:the transabdominal stage and the inguinoscrotal stage.Androgens play a crucial role in the second stage by influencing the development of the gubernaculum,a structure that pulls the testis into the scrotum.However,the mechanisms of androgen actions underlying many of the processes associated with gubernaculum development have not been fully elucidated.To identify the androgen-regulated genes,we conducted large-scale gene expression analyses on the gubernaculum harvested from luteinizing hormone/choriogonadotropin receptor knockout(Lhcgr KO)mice,an animal model of inguinoscrotal testis maldescent resulting from androgen deficiency.We found that the expression of secreted protein acidic and rich in cysteine(SPARC)-related modular calcium binding 1(Smoc1)was the most severely suppressed at both the transcript and protein levels,while its expression was the most dramatically induced by testosterone administration in the gubernacula of Lhcgr KO mice.The upregulation of Smoc1 expression by testosterone was curtailed by the addition of an androgen receptor antagonist,flutamide.In addition,in vitro studies demonstrated that SMOC1 modestly but significantly promoted the proliferation of gubernacular cells.In the cultures of myogenic differentiation medium,both testosterone and SMOC1 enhanced the expression of myogenic regulatory factors such as paired box 7(Pax7)and myogenic factor 5(Myf5).After short-interfering RNA-mediated knocking down of Smoc1,the expression of Pax7 and Myf5 diminished,and testosterone alone did not recover,but additional SMOC1 did.These observations indicate that SMOC1 is pivotal in mediating androgen action to regulate gubernaculum development during inguinoscrotal testicular descent.
基金supported by the Shenzhen Fundamental Research Program(No.JCYJ20210324121807021).
文摘To investigate the impact of preoperative serum follicle-stimulating hormone(FSH)levels on the probability of testicular sperm retrieval,we conducted a study of nonobstructive azoospermic(NOA)men with different testicular volumes(TVs)who underwent microdissection testicular sperm extraction(micro-TESE).A total of 177 NOA patients undergoing micro-TESE for the first time from April 2019 to November 2022 in Shenzhen Zhongshan Obstetrics and Gynecology Hospital(formerly Shenzhen Zhongshan Urology Hospital,Shenzhen,China)were retrospectively reviewed.The subjects were divided into four groups based on average TV quartiles.Serum hormone levels in each TV group were compared between positive and negative sperm retrieval subgroups.Overall sperm retrieval rate was 57.6%.FSH levels(median[interquartile range])were higher in the positive sperm retrieval subgroup compared with the negative outcome subgroup when average TV was<5 ml(first quartile[Q1:TV<3 ml]:43.32[17.92]IU l^(−1) vs 32.95[18.56]IU l−1,P=0.048;second quartile[Q2:3 ml≤TV<5 ml]:31.31[15.37]IU l^(−1) vs 25.59[18.40]IU l^(−1),P=0.042).Elevated serum FSH levels were associated with successful micro-TESE sperm retrieval in NOA men whose average TVs were<5 ml(adjusted odds ratio[OR]:1.06 per unit increase;95%confidence interval[CI]:1.01–1.11;P=0.011).In men with TVs≥5 ml,larger TVs were associated with lower odds of sperm retrieval(adjusted OR:0.84 per 1 ml increase;95%CI:0.71–0.98;P=0.029).In conclusion,elevated serum FSH levels were associated with positive sperm retrieval in micro-TESE in NOA men with TVs<5 ml.In men with TV≥5 ml,increases in average TVs were associated with lower odds of sperm retrieval.
文摘Objective To investigate the value of the clinical application of fetal testis transplantation with main vessel segment. Methods The testicular transplantation were performed to cure 9 patients suffered from male hyponadism with the fetal testis with main vessel segment as donor tissue. Results Except one, 8 patients had a significantly increased level of serum testosterone, the male secondary sexual characteristics and the sexual desire were improved. The size of testis was larger than before operation. Conclusion Fetal testis transplantation with main vessel segment is a effective method of cure male hyponadism and has great value of clinical application. 2 refs.
文摘Aim： To investigate the distribution of cation channel of sperm 1 （CATSPER1） protein and the presence of CATSPER1 mRNA in human testis and ejaculated spermatozoa. The influence of anti-human CATSPER1 antibody upon human sperm motility was used to evaluate the function of human CATSPER1 and to estimate its possible use as a target for immunocontraception. Methods： Human ejaculated sperm from normozoospermic donors （n = 12） and liquid nitrogen frozen human testis were used for the study of mRNA and protein expression of CATSPER1 by reverse transcription polymerase chain reaction （RT-PCR） and immunohistochemistry, respectively. Spermatozoa from normozoospermic donors （n = 12） were individually processed using a swim-up procedure and were then incubated with CATSPER1 antibody at final concentrations of 20, 4 and 0.8 μg/mL. After 1, 2 and 6 h incubation, progressive motility and fast progressive motility were measured by means of computer-assisted semen analysis. Results： CATSPER1 transcript was detected in both human testis and each human ejaculated semen sample. CATSPER1 protein expressed in the membrane of spermatid and was localized in the principal piece of the sperm tail. The application of CATSPER1 antibody at all concentrations significantly inhibited both progressive motility and fast progressive motility after 1, 2 and 6 h incubation, and significant dose-dependent changes were observed. Conclusion： CATSPER1 is meiotically and post-meiotically expressed in human testis tissue. CATSPER1 mRNA in human ejaculated spermatozoa could be a more feasible target for study and infertility screening than testis biopsy. In addition, our results suggest that human CATSPER1 could be a possible target for immunocontraception.
文摘Aim： To examine the effects of melatonin treatment on lipid peroxidation （LPO） and the activities of antioxidant enzymes in the testicular tissue of streptozotocin （STZ）-induced diabetic rats. Methods： Twenty-six male rats were randomly divided into three groups as follows： group Ⅰ, control, non-diabetic rats （n = 9）; group Ⅱ, STZ-induced, untreated diabetic rats （n = 8）; group Ⅲ, STZ-induced, melatonin-treated （dose of 10 mg/kg·day） diabetic rats （n = 9）. Following 8-week melatonin treatment, all rats were anaesthetized and then were killed to remove testes from the scrotum. Results： As compared to group Ⅰ, in rat testicular tissues of grouap Ⅱ, increased levels of malondialdehyde （MDA） （P 〈 0.01） and superoxide dismutase （SOD） （P 〈 0.01） as well as, decreased levels of catalase （CAT） （P 〈 0.01） and glutathione peroxidase （GSH-Px） （P 〉 0.05） were found. In contrast, as compared to group Ⅱ, in rat testicular tissues of group Ⅲ, levels of MDA decreased （but this decrease was not significant, P 〉 0.05） and SOD （P 〈 0.01） as well as CAT （P 〈 0.05） increased. GSH-Px was not influenced by any of the treatment. Melatonin did not significantly affect the elevated glucose concentration of diabetic group. At the end of the study, there was no significant difference between the melatonin-treated group and the untreated group by means of body and testicular weight. Conclusion： Diabetes mellitus increases oxidative stress and melatonin inhibits lipid peroxidation and might regulate the activities of antioxidant enzymes of diabetic rat testes.
文摘<abstract>Aim: To study the expression and regulation of Smadl, Smad2 and Smad4 proteins (intracellular signaling molecules of transforming growth factor-β family) in rat testis during postnatal development. Methods: The whole testes were collected from SD rats aged 3, 7, 14, 28 and 90 (adult) days. The cellular localization and developmental changes were examined by immunohistochemistry ABC method with the glucose oxidase-DAB-nickel enhancement technique. Quantitative analysis of the immunostaining was made by the image analysis system. The Smads proteins coexistence in the adult rat testis was tested by the double immune staining for CD14-Smad4 and Smad2-Smad4. The protein expression of Smad during rat testicular development was examined by means of Western blots. Results: Smadl, Smad2 and Smad4 were present throughout testicular development. The immunostaining of Smadl and Smad2 were present in spermatogenic cells. A positive immunoreactivity was located at the cytoplasm, but the nucleus was negative. Smadl was immunolocalized at the d14, d28 and adult testes, while Smad2, at the d7, d14, d28 and adult testis. There was positive irnmunoreaction in the Sertoli cells and Leydig cells as well. The immunolocalization of Smad4 was exclusively at the cytoplasm of Leydig cells and the nuclei were negative throughout the testicular development. No expression was detected in the germ cells. The results of image and statistical analysis showed that generally the expression of Smadl, Smad2 and Smad4 in the testis tended to increase gradually with the growth of the rat. Conclusion: The present data provide direct evidences for the molecular mechanism of TGF-βaction in rat testes during postnatal development and spermatogenesis.
文摘Aim： To quantitatively study the histological changes of the testis and epididymis as a result of a drastic reduction of testosterone secretion. Methods： Fourteen adult Sprague-Dawley rats were injected intraperitoneally with ethane dimethane sulfonate （EDS, 75 mg/kg） and the same number of animals were injected with normal saline as a control. At days 7 and 12 （after treatment）, respectively, half of the animals from each group were killed. The testes and epididymides were removed and tissue blocks embedded in methacrylate resin. The cell number per testis was estimated using the stereological optical disector and some other parameters were obtained using other morphometric methods. Results： The EDS treatment resulted in an almost complete elimination of Leydig cells but had no effect on the numbers of Sertoli cells per testis. At day 7 after EDS treatment, many elongated spermatids were retained in the seminiferous epithelium and many round spermatids could be seen in the epididymal ducts. At day 12, a looser arrangement of spermatids and spermatocytes became evident, with apparent narrow empty spaces being formed between germ cells in an approximately radial direction towards the tubule lumen; the numbers （per testis） of non-type B spermatogonia and spermatocytes were similar to controls, whereas that of type B spermatogonia increased by 59%, and that of early round, elongating and late elongated spermatids decreased by 37%, 72% and 52%, respectively. Conclusion： The primary spermatogenic lesions following EDS administration were （i） spermiation failure and （ii） detachment of spermatids and spermatocytes associated with impairment in spermiogenesis and meiosis.
文摘For centuries, plants and plant-based products have been used as a valuable and safe natural source of medicines for treating various ailments. The therapeutic potential of most of these plants could be ascribed to their anticancer, antidiabetic, hepatoprotective, cardioprotective, antispasmodic, analgesic and various other pharmacological properties. However, several commonly used plants have been reported to adversely affect male reproductive functions in wildlife and humans. The effects observed with most of the plant and plant-based products have been attributed to the antispermatogenic and/or antisteroidogenic properties of one or more active ingredients. This review discusses the detrimental effects of some of the commonly used plants on various target cells in the testis. A deeper insight into the molecular mechanisms of action of these natural compounds could pave the way for developing therapeutic strategies against their toxicity.
基金Indo-UK Cancer Research ProgramNo.BT/IN/UK/NII/2006+3 种基金Centre for Molecular MedicineNo.BT/PR/14549/MED/14/1291NII-core funding,Department of BiotechnologyGovernment of India
文摘Colorectal cancer ranks third among the estimatedcancer cases and cancer related mortalities in United States in 2014. Early detection and efficient therapy remains a significant clinical challenge for this disease. Therefore, there is a need to identify novel tumor asso-ciated molecules to target for biomarker development and immunotherapy. In this regard, cancer testis antigens have emerged as a potential targets for developing novel clinical biomarkers and immunotherapy for various malignancies. These germ cell specific proteins exhibit aberrant expression in cancer cells and contribute in tumorigenesis. Owing to their unique expression profile and immunogenicity in cancer patients, cancer testis antigens are clinically referred as the most promising tumor associated antigens. Several cancer testis antigens have been studied in colorectal cancer but none of them could be used in clinical practice. This review is an attempt to address the promising cancer testis antigens in colorectal cancer and their possible clinical implications as biomarkers and immunotherapeutic targets with particular focus on challenges and future interventions.
文摘Successful spermatogonial transplantation requires depletion of the host germ cells to allow efficient colonization of the donor spermatogonial stem cells. Although a sterilizing drug,busulfan （Myleran）,is commonly used for preparing a recipient mouse before transplantation,the optimal dose of this drug has not yet been defined.The present study investigated the effects of different doses of busulfan （10-50 mg per kg body weight） on survival rate,testicular mass and histomorphology,and on the haploid spermatids and spermatozoa of male BALB/c mice.The results suggest that a dosage of 30 mg kg^-1 is optimal for the ablative treatment withbusulfan used to prepare the recipient mice. This dose results in an adequate depletion of the host germ cells for colonization of donorderived spermatogonial stem cells and causes the lowest death rate of the animals.
文摘Aim:To identify and characterize a novel gene with potential roles in testis development and spermatogenesis. Methods:A cDNA microarray was constructed from a human testis large insert cDNA library and hybridized with probes of human or mouse adult and fetal testes.Differentially expressed genes were isolated and sequenced.RT-PCR was used to test the tissue distribution of the genes of interest and in situ hybridization was performed to localize the gene expression in the mouse testis.A range of bioinformatical programs including Gene Runner,SMART,NCBI Blast and Emboss CpGPlot were used to characterize the new gene's feature.Results:A novel testis-specific gene, NYD-SP5,was differentially expressed in fetal and adult testes.The deduced protein structure of NYD-SP5 was found to contain an IQ motif (a short calmodulin-binding motif containing conserved lie and Gin residues),a Carbam- ate kinase-like domain,a Zn-dependent exopeptidase domain and a lactate dehydrogenase (LDH) C-terminal-like domain.RT-PCR analysis revealed that NYD-SP5 was predominantly expressed in the testis but not in other 15 tissues examined.In situ hybridization and RT-PCR examinations revealed that the expression of NYD-SP5 was confined in the male germ cell but not present in the somatic cell in the testes.Conclusion:NYD-SP5 is a newly found testis- specific gene with potential roles in testis development and spermatogenesis through a calmodulin-activated enzyme.
文摘Aim: To evaluate the effect of oxidative stress on the spermatogenesis and lactate dehydrogenase-X (LDH-X) activity in mouse testis. Methods: For creating different levels of oxidative stress in mice, three selenium (Se) level diets were fed in separate groups for 8 weeks. Group 1 animals were fed yeast-based Se-deficient (0.02 ppm) diet. Group 2 and Group 3 animals were fed with the same diet supplemented with 0.2 ppm and 1 ppm Se as sodium selenite, respectively. After 8 weeks, biochemical and histopathological observations of the testis were carried out. LDH-X levels in the testis were analyzed by western immunoblot and ELISA. Results: A significant decrease in testis Se level was observed in Group 1 animals, whereas it was enhanced in Group 3 as compared to Group 2. The glutathione peroxidase (GSH-Px) activity was significantly reduced in both the liver and testis in Group 1, but not in Group 2 and 3. A significant increase in the testis glutathione-S-transferase (GST) activity was observed in Group 1, whereas no significant change was seen in Groups 2 and 3. Histological analysis of testis revealed a normal structure in Group 2. A significant decrease in the germ cell population in Group 1 was observed as compared to Group 2 with the spermatids and mature sperm affected the most. Decrease in the lumen size was also observed. In the Se-excess group (Group 3), displacement of germ cell population was observed. Further, a decrease in the LDH-X level in testis was observed in Group 1. Conclusion: Excessive oxidative stress in the Se deficient group, as indicated by changes in the GSH-Px/GST activity, affects the spermatogenic process with a reduction in mature sperm and in turn the LDH-X level.
