Background Hexafluoropropylene oxide dimer acid(GenX),a substitute for per-and polyfluoroalkyl substances,has been widely detected in various environmental matrices and foods recently,attracting great attention.Howeve...Background Hexafluoropropylene oxide dimer acid(GenX),a substitute for per-and polyfluoroalkyl substances,has been widely detected in various environmental matrices and foods recently,attracting great attention.However,a systematic characterization of its reproductive toxicity is still missing.This study aims to explore the male reproductive toxicity caused by GenX exposure and the potential cellular and molecular regulatory mechanisms behind it.Results Normally developing mice were exposed to GenX,and testicular tissue was subsequently analyzed and validated using single-cell RNA sequencing.Our results revealed that GenX induced severe testicular damage,disrupted the balance between undifferentiated and differentiated spermatogonial stem cells,and led to strong variation in the cellular dynamics of spermatogenesis.Furthermore,GenX exposure caused global upregulation of testicular somatic cellular inflammatory responses,increased abnormal macrophage differentiation,and attenuated fibroblast adhesion,disorganizing the somatic-germline interactions.Conclusions In conclusion,this study revealed complex cellular dynamics and transcriptome changes in mouse testis after GenX exposure,providing a valuable resource for understanding its reproductive toxicity.展开更多
Male dzo from the F1 to F3 generations are sterile,which impedes the utilization of hybrid vigor in dzo and constrains the development of plateau animal husbandry in China.The underlying mechanism of this phenomenon h...Male dzo from the F1 to F3 generations are sterile,which impedes the utilization of hybrid vigor in dzo and constrains the development of plateau animal husbandry in China.The underlying mechanism of this phenomenon has long been a focal point in yak crossbreeding improvement research.This review summarizes the mechanisms underlying male sterility in dzo from histological,physiological,and multi-omics perspectives,providing research directions for further exploration of the mechanisms of male sterility in dzo.展开更多
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
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
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
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
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
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
BACKGROUND Spigelian hernia(SH),a protrusion of intra-abdominal contents through a defect in the semilunar line(Spigelian fascia)of the abdominal wall,is extremely rare in the pediatric population.Fewer than 100 cases...BACKGROUND Spigelian hernia(SH),a protrusion of intra-abdominal contents through a defect in the semilunar line(Spigelian fascia)of the abdominal wall,is extremely rare in the pediatric population.Fewer than 100 cases of pediatric SH have been reported in the literature since the first description in 1939.Pediatric SH is often congenital and may present with non-specific symptoms,making diagnosis challenging.Notably,about one-quarter to one-third of reported pediatric cases are associated with ipsilateral undescended testis,an association sometimes termed the"Spigelian-cryptorchidism syndrome".AIM To systematically review all reported cases of Spigelian hernia in children and identify its diagnostic and surgical features.METHODS A comprehensive literature search was performed(1939 through 2023)using PubMed and other databases for all publications on Spigelian(semilunar line)hernias in children.Both English and non-English articles were included.Case reports,case series,and relevant reviews were analyzed.Data extracted included patient demographics,hernia side/location,clinical features,imaging and intraoperative findings,coexisting conditions(particularly cryptorchidism),management(open vs laparoscopic repair),and outcomes.RESULTS A total of approximately 90 pediatric SH cases from 44 publications were identified.The median age at presentation was around 3-4 years(range:Neonate to 17 years).Slight male predominance was observed,although SH also occurs in females.About 30%of cases involved an ipsilateral undescended testis within the hernia sac or in the Spigelian region.Rare associations with other anomalies were noted,including concurrent inguinal hernias,umbilical hernia,and even complex syndromic presentations(for example,limb defects,neuroblastoma)in a few cases.Clinical presentation often included a reducible lump or intermittent bulge along the lateral aspect of the lower abdomen,sometimes misdiagnosed as an inguinal hernia.Recurrent localized abdominal pain was a frequent symptom,and some infants presented with acute intestinal obstruction from incarcerated SH.Diagnosis was most commonly established by ultrasound,which is considered the gold standard imaging modality for SH in children due to its ability to detect fascial defects and herniated tissue dynamically.A subset of cases(approximately 10%)were attributed to blunt abdominal trauma(for example,bicycle handlebar injury),causing an acquired SH.Management:All reported pediatric SHs were treated surgically,given the high risk of incarceration.Open hernia repair through a small transverse incision over the defect was the traditional approach,and no recurrences have been reported after adequate fascial closure.Over the last decade,laparoscopic repair has become the method of choice,especially for cases combined with an undescended testis,allowing simultaneous orchiopexy.Laparoscopic techniques have been successful in safely reducing the hernia and closing the defect,with excellent outcomes and minimal morbidity.CONCLUSION Spigelian hernia in children is a rare but clinically important entity that should be considered in cases of unexplained recurrent abdominal pain,lateral abdominal wall swelling,or cryptorchidism.Early recognition using high-resolution ultrasound and prompt surgical intervention are critical to prevent life-threatening incarceration.Congenital defect of the Spigelian fascia underlies most pediatric cases,and the frequent association with ipsilateral undescended testis suggests a developmental interplay.Surgical repair has excellent outcomes.Increased awareness of pediatric SH among clinicians is necessary to ensure timely diagnosis and treatment,thereby avoiding complications and improving patient outcomes.展开更多
Chinese labs begin R&D for Big Pharma and other biotech companies It came down to three countries for Bridge Pharmaceuticals' new animal testing lab: India, Singapore and China. In the process India fell out o...Chinese labs begin R&D for Big Pharma and other biotech companies It came down to three countries for Bridge Pharmaceuticals' new animal testing lab: India, Singapore and China. In the process India fell out of the equation. "India doesn't have primates or dogs," said Glenn Rice, the Menlo Park, California-based company's president and CEO. India is a great place for small molecule manufacturing but not for toxicology testing on animals because the right breeders are not available there,展开更多
BACKGROUND Colorectal cancer(CRC)is the third most common cancer and a significant cause of cancer-related mortality globally.Resistance to chemotherapy,especially during CRC treatment,leads to reduced effectiveness o...BACKGROUND Colorectal cancer(CRC)is the third most common cancer and a significant cause of cancer-related mortality globally.Resistance to chemotherapy,especially during CRC treatment,leads to reduced effectiveness of drugs and poor patient outcomes.Long noncoding RNAs(lncRNAs)have been implicated in various pathophysiological processes of tumor cells,including chemotherapy resistance,yet the roles of many lncRNAs in CRC remain unclear.AIM To identify and analyze the lncRNAs involved in oxaliplatin resistance in CRC and to understand the underlying molecular mechanisms influencing this resistance.METHODS Gene Expression Omnibus datasets GSE42387 and GSE30011 were reanalyzed to identify lncRNAs and mRNAs associated with oxaliplatin resistance.Various bioinformatics tools were employed to elucidate molecular mechanisms.The expression levels of lncRNAs and mRNAs were assessed via quantitative reverse transcription-polymerase chain reaction.Functional assays,including MTT,wound healing,and Transwell,were conducted to investigate the functional implications of lncRNA alterations.Interactions between lncRNAs and trans-cription factors were examined using RIP and luciferase reporter assays,while Western blotting was used to confirm downstream pathways.Additionally,a xenograft mouse model was utilized to study the in vivo effects of lncRNAs on chemotherapy resistance.RESULTS LncRNA prion protein testis specific(PRNT)was found to be upregulated in oxaliplatin-resistant CRC cell lines and negatively correlated with homeodomain interacting protein kinase 2(HIPK2)expression.PRNT was demonstrated to sponge transcription factor zinc finger protein 184(ZNF184),which in turn could regulate HIPK2 expression.Altered expression of PRNT influenced CRC cell sensitivity to oxaliplatin,with overexpression leading to decreased sensitivity and decreased expression reducing resistance.Both RIP and luciferase reporter assays indicated that ZNF184 and HIPK2 are targets of PRNT.The PRNT/ZNF184/HIPK2 axis was implicated in promoting CRC progression and oxaliplatin resistance both in vitro and in vivo.CONCLUSION The study concludes that PRNT is upregulated in oxaliplatin-resistant CRC cells and modulates the expression of HIPK2 by sponging ZNF184.This regulatory mechanism enhances CRC progression and resistance to oxaliplatin,positioning PRNT as a promising therapeutic target for CRC patients undergoing oxaliplatin-based chemotherapy.展开更多
Testicular development is an important biological process in male and requires interaction between the male germ cells and somatic cells.However,the mechanisms of testicular development in livestock,particularly in ca...Testicular development is an important biological process in male and requires interaction between the male germ cells and somatic cells.However,the mechanisms of testicular development in livestock,particularly in cattle,are poorly understood.Furthermore,cellular heterogeneity hinders the profiling of different cell types at different developmental stages.In this study,we first performed a single-cell transcriptomic study of the bovine testis development during puberty by using 10×genomics single-cell RNA sequencing(scRNA-seq).By collecting the scRNA-seq data from 11,083 cells from prepubertal and pubertal bovine testes,a high-resolution scRNA-seq atlas was described,identifying 9 somatic and 13 spermatogenic clusters.We also distinguished several stage-specific marker genes for bovine germ cells and somatic cells,such as GRAF2 and MORC1 for SSC(spermatogonial stem cells),HJURP and TCF19 for differentiating spermatogonia,ARSE for immature Sertoli,CLEC12B for mature Sertoli,LOC112441470 for Leydig.In conclusion,we have examined the transcription levels and constructed the single-cell developmental maps of germ cells and somatic cells during testicular development in Angus cattle.The datasets provided new insights into spermatogenesis and testicular somatic cell development in cattle.展开更多
Cuproptosis,a novel mechanism of programmed cell death,has not been fully explored in the context of spermatogenic cells.Thisstudy investigated the potential involvement of cuproptosis in spermatogenic cell death usin...Cuproptosis,a novel mechanism of programmed cell death,has not been fully explored in the context of spermatogenic cells.Thisstudy investigated the potential involvement of cuproptosis in spermatogenic cell death using a mouse model of copper overload.Sixty male Institute of Cancer Research(ICR)mice were randomly divided into four groups that received daily oral gavage withsodium chloride(control)or copper sulfate(CuSO_(4))at 50 mg kg^(−1),100 mg kg^(−1),or 200 mg kg^(−1),for 42 consecutive days.Micesubjected to copper overload exhibited a disruption in copper homeostasis.Additionally,significant upregulated expression of keycuproptosis factors was accompanied by a significant rise in the rates of testicular tissue cell apoptosis.Immunohistochemicalanalysis revealed the presence of ferredoxin 1(Fdx1)in Sertoli cells,Leydig cells,and spermatogenic cells at various stages oftesticular development,and the Fdx1-positive staining area was significantly increased in copper-overloaded mice.Mitochondrialdysfunction and decreased adenosine triphosphate levels were also observed,further implicating mitochondrial damage undercuproptosis.Further analyses revealed pathological lesions and blood−testis barrier destruction in the testicular tissue,accompaniedby decreased sperm concentration and motility,in copper-overloaded mice.In summary,our results indicate that copper-overloadedmice exhibit copper homeostasis disorder in the testicular tissue and that cuproptosis participates in spermatogenic cell death.These findings provide novel insights into the pathogenic mechanisms underlying spermatogenic cell death and provide initialexperimental evidence for the occurrence of cuproptosis in the testis.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
Objective:To evaluate the protective effects of probiotic microorganisms on the reproductive and nervous systems of male rats treated with acrylamide.Methods:Thirty-two rats were randomly divided into 4 groups and rec...Objective:To evaluate the protective effects of probiotic microorganisms on the reproductive and nervous systems of male rats treated with acrylamide.Methods:Thirty-two rats were randomly divided into 4 groups and received normal saline through gavage(control),acrylamide 20 mg/kg body weight,acrylamide plus probiotic microorganisms(Lactobacillus acidophilus,Lactobacillus casei,Lactobacillus bulgaricus,Lactobacillus rhamnosus,Bifidobacterium breve,Bifidobacterium infantis,Streptococcus thermophilus and fructooligosaccharides,all mixed in sachets)20 or 200 mg/kg body weight,respectively.After 30 days,the testis,prostate,seminal vesicle and cerebellum were removed,fixed and stained with hematoxylin-eosin(H&E).The Johnsen score was used to classify spermatogenesis.Cavalieri's principle method was used to evaluate the total volume(in mm3)of the testes.The number of each intratubular cell type as well as intertubular Leydig cells in whole samples was measured using the physical dissector counting techniques.Stereological analysis and the grids were used to determine the volume of cerebellar layers as well as the Purkinje cell number.Results:The testis weight decreased significantly in the acrylamide-treated group compared to the other groups(P<0.001).The number of spermatogonia,spermatocytes,spermatids and Leydig cells in the acrylamide-treated group were significantly less compared to the control group(P<0.05),while they were increased significantly in the acrylamide+200 mg/kg probiotic group(P<0.05;P<0.01).The mean Johnsen score in the acrylamide-treated group was lower than in the control group(P<0.001).Acrylamide-induced changes including congestion,vacuolization in the secretory epithelial cells,and epithelial rupture were observed in the prostate and seminal vesicle.The volumes of cerebellar layers were decreased in the acrylamide group compared to the control group while recovered in both probiotic treated groups.Conclusions:Probiotic microorganisms alleviate acrylamide-induced toxicities against the reproductive and cerebellar tissues in rats.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
BACKGROUND The incidence of monodermal teratomas of the reproductive system is low,and most doctors lack adequate understanding,which can easily lead to missed diagnoses and/or misdiagnosis.Therefore,it is important t...BACKGROUND The incidence of monodermal teratomas of the reproductive system is low,and most doctors lack adequate understanding,which can easily lead to missed diagnoses and/or misdiagnosis.Therefore,it is important to fully understand the clinical characteristics,diagnosis,differential diagnosis,and treatment of monodermal teratomas of the reproductive system.CASE SUMMARY Case 1:A 14-year-old boy was admitted to the hospital with a right testicular mass for 1 wk and underwent surgical resection.He was finally diagnosed with right testicular monodermal teratoma with no special postoperative discomfort.Case 2:A 40-year-old woman was admitted to the hospital for uterine abnormalities indicated by ultrasound 20 d prior and underwent laparoscopic surgery.She was finally diagnosed with a left ovarian monodermal teratoma with a satisfactory postoperative quality of life.Case 3:A 49-year-old woman was admitted to the hospital with a pelvic mass that was discovered on B-ultrasound a week prior and underwent laparoscopic resection of the left adnexa.She was finally diagnosed with left ovarian monodermal teratoma,and her postoperative quality of life was satisfactory.CONCLUSION Monodermal teratoma is a rare tumor whose clinical manifestations are primarily benign.Simple surgical resection of the tumor is effective.展开更多
Objective:Cryptorchidism affects up to 6% of full-term male infants, and orchidopexy has been shown to reduce impaired spermatogenesis and malignant risks significantly. However, the relationship between orchidopexy a...Objective:Cryptorchidism affects up to 6% of full-term male infants, and orchidopexy has been shown to reduce impaired spermatogenesis and malignant risks significantly. However, the relationship between orchidopexy and sexual function has not been investigated. Therefore, this study aimed to evaluate sexual function outcomes in adult patients who underwent orchidopexy for unilateral undescended testis in childhood.Methods:Totally, 58 adult patients who underwent unilateral orchidopexy in childhood were enrolled in the study. Erectile dysfunction (ED) was assessed by the International Index of Erectile Function (IIEF)-15 questionnaire. All participants underwent serum (testosterone and follicular stimulating hormone levels) measurement and semen analysis. Paternity rates were evaluated to assess the patient's fertility. Additionally, anxiety, depression, and stress were measured by the self-rating anxiety scale, self-rating depression scale, and visual analogue scale, respectively.Results:There was no statistically significant difference between IIEF-15 scores (intercourse satisfaction, orgasmic function, sexual desire, or overall satisfaction) comparing the cryptorchidism group with the control group;however, the ED was significantly higher in the cryptorchidism patients (p=0.000). At the median follow-up of 16.3 years, 15.5% of our patients complained of moderate to severe ED. Most patients were satisfied with their overall relationship and only 34.5% were not satisfied. Anxiety, depression, and stress were more prevalent in cryptorchidism than in healthy men (anxiety: 72.4% vs. 20.7%;depression: 19.0% vs. 5.2%;stress: 60.3% vs. 10.3%;p<0.05). Additionally, ED was negatively associated with anxiety, depression, and stress symptoms (r=−0.518, p=0.000;r=−0.448, p=0.000;r=−0.591, p=0.000, respectively). Moreover, ED had a significant correlation with advancing age, psychological factors (anxiety, depression, and stress), infertility, and low levels of testosterone (p<0.05).Conclusion:Low testosterone, infertility, and psychological burden (anxiety, depression, and stress) are used as factors for predicting ED outcomes after orchidopexy for undescended testis to guide physicians to evaluate the efficacy of testosterone replacement and psychological support in their management.展开更多
基金supported by the Guangdong Provincial Key Area Research and Development Program[grant number 2022B0202090002]China Postdoctoral Science Foundation[grant number 2024M760977].
文摘Background Hexafluoropropylene oxide dimer acid(GenX),a substitute for per-and polyfluoroalkyl substances,has been widely detected in various environmental matrices and foods recently,attracting great attention.However,a systematic characterization of its reproductive toxicity is still missing.This study aims to explore the male reproductive toxicity caused by GenX exposure and the potential cellular and molecular regulatory mechanisms behind it.Results Normally developing mice were exposed to GenX,and testicular tissue was subsequently analyzed and validated using single-cell RNA sequencing.Our results revealed that GenX induced severe testicular damage,disrupted the balance between undifferentiated and differentiated spermatogonial stem cells,and led to strong variation in the cellular dynamics of spermatogenesis.Furthermore,GenX exposure caused global upregulation of testicular somatic cellular inflammatory responses,increased abnormal macrophage differentiation,and attenuated fibroblast adhesion,disorganizing the somatic-germline interactions.Conclusions In conclusion,this study revealed complex cellular dynamics and transcriptome changes in mouse testis after GenX exposure,providing a valuable resource for understanding its reproductive toxicity.
基金Supported by Sichuan Beef Cattle Innovation Team Construction Project of National Modern Agricultural Industry Technology System(SCCXTD-2025-13)Yaan City's"Challenge Prize Mechanism for Key Technologies"Project for Creating a National Modern Agricultural Industry Technology Innovation Center-Breeding of New Local Beef Cattle Groups in Yaan(kczx2023-2025-18)+1 种基金Yaan City's"Challenge Prize Mechanism for Key Technologies"Project for Creating a National Modern Agricultural Industry Technology Innovation Center-Integrated Application of High-Quality Beef Cattle Development Technology System(kczx2023-2025-22)Yaan City's"Challenge Prize Mechanism for Key Technologies"Project for Creating a National Modern Agricultural Industry Technology Innovation Center-Research and Integration of Key Technologies for Informatization in Yaan Beef Cattle Production(kczx2023-2025-26).
文摘Male dzo from the F1 to F3 generations are sterile,which impedes the utilization of hybrid vigor in dzo and constrains the development of plateau animal husbandry in China.The underlying mechanism of this phenomenon has long been a focal point in yak crossbreeding improvement research.This review summarizes the mechanisms underlying male sterility in dzo from histological,physiological,and multi-omics perspectives,providing research directions for further exploration of the mechanisms of male sterility in dzo.
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.
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 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BACKGROUND Spigelian hernia(SH),a protrusion of intra-abdominal contents through a defect in the semilunar line(Spigelian fascia)of the abdominal wall,is extremely rare in the pediatric population.Fewer than 100 cases of pediatric SH have been reported in the literature since the first description in 1939.Pediatric SH is often congenital and may present with non-specific symptoms,making diagnosis challenging.Notably,about one-quarter to one-third of reported pediatric cases are associated with ipsilateral undescended testis,an association sometimes termed the"Spigelian-cryptorchidism syndrome".AIM To systematically review all reported cases of Spigelian hernia in children and identify its diagnostic and surgical features.METHODS A comprehensive literature search was performed(1939 through 2023)using PubMed and other databases for all publications on Spigelian(semilunar line)hernias in children.Both English and non-English articles were included.Case reports,case series,and relevant reviews were analyzed.Data extracted included patient demographics,hernia side/location,clinical features,imaging and intraoperative findings,coexisting conditions(particularly cryptorchidism),management(open vs laparoscopic repair),and outcomes.RESULTS A total of approximately 90 pediatric SH cases from 44 publications were identified.The median age at presentation was around 3-4 years(range:Neonate to 17 years).Slight male predominance was observed,although SH also occurs in females.About 30%of cases involved an ipsilateral undescended testis within the hernia sac or in the Spigelian region.Rare associations with other anomalies were noted,including concurrent inguinal hernias,umbilical hernia,and even complex syndromic presentations(for example,limb defects,neuroblastoma)in a few cases.Clinical presentation often included a reducible lump or intermittent bulge along the lateral aspect of the lower abdomen,sometimes misdiagnosed as an inguinal hernia.Recurrent localized abdominal pain was a frequent symptom,and some infants presented with acute intestinal obstruction from incarcerated SH.Diagnosis was most commonly established by ultrasound,which is considered the gold standard imaging modality for SH in children due to its ability to detect fascial defects and herniated tissue dynamically.A subset of cases(approximately 10%)were attributed to blunt abdominal trauma(for example,bicycle handlebar injury),causing an acquired SH.Management:All reported pediatric SHs were treated surgically,given the high risk of incarceration.Open hernia repair through a small transverse incision over the defect was the traditional approach,and no recurrences have been reported after adequate fascial closure.Over the last decade,laparoscopic repair has become the method of choice,especially for cases combined with an undescended testis,allowing simultaneous orchiopexy.Laparoscopic techniques have been successful in safely reducing the hernia and closing the defect,with excellent outcomes and minimal morbidity.CONCLUSION Spigelian hernia in children is a rare but clinically important entity that should be considered in cases of unexplained recurrent abdominal pain,lateral abdominal wall swelling,or cryptorchidism.Early recognition using high-resolution ultrasound and prompt surgical intervention are critical to prevent life-threatening incarceration.Congenital defect of the Spigelian fascia underlies most pediatric cases,and the frequent association with ipsilateral undescended testis suggests a developmental interplay.Surgical repair has excellent outcomes.Increased awareness of pediatric SH among clinicians is necessary to ensure timely diagnosis and treatment,thereby avoiding complications and improving patient outcomes.
文摘Chinese labs begin R&D for Big Pharma and other biotech companies It came down to three countries for Bridge Pharmaceuticals' new animal testing lab: India, Singapore and China. In the process India fell out of the equation. "India doesn't have primates or dogs," said Glenn Rice, the Menlo Park, California-based company's president and CEO. India is a great place for small molecule manufacturing but not for toxicology testing on animals because the right breeders are not available there,
基金Supported by Hebei Provincial Health Commission Youth Science and Technology Project,No.20210027.
文摘BACKGROUND Colorectal cancer(CRC)is the third most common cancer and a significant cause of cancer-related mortality globally.Resistance to chemotherapy,especially during CRC treatment,leads to reduced effectiveness of drugs and poor patient outcomes.Long noncoding RNAs(lncRNAs)have been implicated in various pathophysiological processes of tumor cells,including chemotherapy resistance,yet the roles of many lncRNAs in CRC remain unclear.AIM To identify and analyze the lncRNAs involved in oxaliplatin resistance in CRC and to understand the underlying molecular mechanisms influencing this resistance.METHODS Gene Expression Omnibus datasets GSE42387 and GSE30011 were reanalyzed to identify lncRNAs and mRNAs associated with oxaliplatin resistance.Various bioinformatics tools were employed to elucidate molecular mechanisms.The expression levels of lncRNAs and mRNAs were assessed via quantitative reverse transcription-polymerase chain reaction.Functional assays,including MTT,wound healing,and Transwell,were conducted to investigate the functional implications of lncRNA alterations.Interactions between lncRNAs and trans-cription factors were examined using RIP and luciferase reporter assays,while Western blotting was used to confirm downstream pathways.Additionally,a xenograft mouse model was utilized to study the in vivo effects of lncRNAs on chemotherapy resistance.RESULTS LncRNA prion protein testis specific(PRNT)was found to be upregulated in oxaliplatin-resistant CRC cell lines and negatively correlated with homeodomain interacting protein kinase 2(HIPK2)expression.PRNT was demonstrated to sponge transcription factor zinc finger protein 184(ZNF184),which in turn could regulate HIPK2 expression.Altered expression of PRNT influenced CRC cell sensitivity to oxaliplatin,with overexpression leading to decreased sensitivity and decreased expression reducing resistance.Both RIP and luciferase reporter assays indicated that ZNF184 and HIPK2 are targets of PRNT.The PRNT/ZNF184/HIPK2 axis was implicated in promoting CRC progression and oxaliplatin resistance both in vitro and in vivo.CONCLUSION The study concludes that PRNT is upregulated in oxaliplatin-resistant CRC cells and modulates the expression of HIPK2 by sponging ZNF184.This regulatory mechanism enhances CRC progression and resistance to oxaliplatin,positioning PRNT as a promising therapeutic target for CRC patients undergoing oxaliplatin-based chemotherapy.
基金supported by the National Natural Science Foundation of China(81770514)the 2020 Scientist Plus Engineer Program of Shaanxi Province,China(K4050422468)+2 种基金the Key Research&Development Plan of Shaanxi Province,China(2020NY-002)the Natural Science Basis Research Plan of Shaanxi Province,China(2023-JC-QN-0242)the China Agriculture Research System of MOF and MARA(CARS-37)。
文摘Testicular development is an important biological process in male and requires interaction between the male germ cells and somatic cells.However,the mechanisms of testicular development in livestock,particularly in cattle,are poorly understood.Furthermore,cellular heterogeneity hinders the profiling of different cell types at different developmental stages.In this study,we first performed a single-cell transcriptomic study of the bovine testis development during puberty by using 10×genomics single-cell RNA sequencing(scRNA-seq).By collecting the scRNA-seq data from 11,083 cells from prepubertal and pubertal bovine testes,a high-resolution scRNA-seq atlas was described,identifying 9 somatic and 13 spermatogenic clusters.We also distinguished several stage-specific marker genes for bovine germ cells and somatic cells,such as GRAF2 and MORC1 for SSC(spermatogonial stem cells),HJURP and TCF19 for differentiating spermatogonia,ARSE for immature Sertoli,CLEC12B for mature Sertoli,LOC112441470 for Leydig.In conclusion,we have examined the transcription levels and constructed the single-cell developmental maps of germ cells and somatic cells during testicular development in Angus cattle.The datasets provided new insights into spermatogenesis and testicular somatic cell development in cattle.
基金supported by the National Natural Science Foundation ofChina(No.81973647 and No.82274325)the Chengdu Municipal HealthCommission(No.2023215).
文摘Cuproptosis,a novel mechanism of programmed cell death,has not been fully explored in the context of spermatogenic cells.Thisstudy investigated the potential involvement of cuproptosis in spermatogenic cell death using a mouse model of copper overload.Sixty male Institute of Cancer Research(ICR)mice were randomly divided into four groups that received daily oral gavage withsodium chloride(control)or copper sulfate(CuSO_(4))at 50 mg kg^(−1),100 mg kg^(−1),or 200 mg kg^(−1),for 42 consecutive days.Micesubjected to copper overload exhibited a disruption in copper homeostasis.Additionally,significant upregulated expression of keycuproptosis factors was accompanied by a significant rise in the rates of testicular tissue cell apoptosis.Immunohistochemicalanalysis revealed the presence of ferredoxin 1(Fdx1)in Sertoli cells,Leydig cells,and spermatogenic cells at various stages oftesticular development,and the Fdx1-positive staining area was significantly increased in copper-overloaded mice.Mitochondrialdysfunction and decreased adenosine triphosphate levels were also observed,further implicating mitochondrial damage undercuproptosis.Further analyses revealed pathological lesions and blood−testis barrier destruction in the testicular tissue,accompaniedby decreased sperm concentration and motility,in copper-overloaded mice.In summary,our results indicate that copper-overloadedmice exhibit copper homeostasis disorder in the testicular tissue and that cuproptosis participates in spermatogenic cell death.These findings provide novel insights into the pathogenic mechanisms underlying spermatogenic cell death and provide initialexperimental evidence for the occurrence of cuproptosis in the testis.
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.
基金Shahid Sadoughi University of Medical Sciences,Yazd,Iran(grant number 5689).
文摘Objective:To evaluate the protective effects of probiotic microorganisms on the reproductive and nervous systems of male rats treated with acrylamide.Methods:Thirty-two rats were randomly divided into 4 groups and received normal saline through gavage(control),acrylamide 20 mg/kg body weight,acrylamide plus probiotic microorganisms(Lactobacillus acidophilus,Lactobacillus casei,Lactobacillus bulgaricus,Lactobacillus rhamnosus,Bifidobacterium breve,Bifidobacterium infantis,Streptococcus thermophilus and fructooligosaccharides,all mixed in sachets)20 or 200 mg/kg body weight,respectively.After 30 days,the testis,prostate,seminal vesicle and cerebellum were removed,fixed and stained with hematoxylin-eosin(H&E).The Johnsen score was used to classify spermatogenesis.Cavalieri's principle method was used to evaluate the total volume(in mm3)of the testes.The number of each intratubular cell type as well as intertubular Leydig cells in whole samples was measured using the physical dissector counting techniques.Stereological analysis and the grids were used to determine the volume of cerebellar layers as well as the Purkinje cell number.Results:The testis weight decreased significantly in the acrylamide-treated group compared to the other groups(P<0.001).The number of spermatogonia,spermatocytes,spermatids and Leydig cells in the acrylamide-treated group were significantly less compared to the control group(P<0.05),while they were increased significantly in the acrylamide+200 mg/kg probiotic group(P<0.05;P<0.01).The mean Johnsen score in the acrylamide-treated group was lower than in the control group(P<0.001).Acrylamide-induced changes including congestion,vacuolization in the secretory epithelial cells,and epithelial rupture were observed in the prostate and seminal vesicle.The volumes of cerebellar layers were decreased in the acrylamide group compared to the control group while recovered in both probiotic treated groups.Conclusions:Probiotic microorganisms alleviate acrylamide-induced toxicities against the reproductive and cerebellar tissues in rats.
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BACKGROUND The incidence of monodermal teratomas of the reproductive system is low,and most doctors lack adequate understanding,which can easily lead to missed diagnoses and/or misdiagnosis.Therefore,it is important to fully understand the clinical characteristics,diagnosis,differential diagnosis,and treatment of monodermal teratomas of the reproductive system.CASE SUMMARY Case 1:A 14-year-old boy was admitted to the hospital with a right testicular mass for 1 wk and underwent surgical resection.He was finally diagnosed with right testicular monodermal teratoma with no special postoperative discomfort.Case 2:A 40-year-old woman was admitted to the hospital for uterine abnormalities indicated by ultrasound 20 d prior and underwent laparoscopic surgery.She was finally diagnosed with a left ovarian monodermal teratoma with a satisfactory postoperative quality of life.Case 3:A 49-year-old woman was admitted to the hospital with a pelvic mass that was discovered on B-ultrasound a week prior and underwent laparoscopic resection of the left adnexa.She was finally diagnosed with left ovarian monodermal teratoma,and her postoperative quality of life was satisfactory.CONCLUSION Monodermal teratoma is a rare tumor whose clinical manifestations are primarily benign.Simple surgical resection of the tumor is effective.
文摘Objective:Cryptorchidism affects up to 6% of full-term male infants, and orchidopexy has been shown to reduce impaired spermatogenesis and malignant risks significantly. However, the relationship between orchidopexy and sexual function has not been investigated. Therefore, this study aimed to evaluate sexual function outcomes in adult patients who underwent orchidopexy for unilateral undescended testis in childhood.Methods:Totally, 58 adult patients who underwent unilateral orchidopexy in childhood were enrolled in the study. Erectile dysfunction (ED) was assessed by the International Index of Erectile Function (IIEF)-15 questionnaire. All participants underwent serum (testosterone and follicular stimulating hormone levels) measurement and semen analysis. Paternity rates were evaluated to assess the patient's fertility. Additionally, anxiety, depression, and stress were measured by the self-rating anxiety scale, self-rating depression scale, and visual analogue scale, respectively.Results:There was no statistically significant difference between IIEF-15 scores (intercourse satisfaction, orgasmic function, sexual desire, or overall satisfaction) comparing the cryptorchidism group with the control group;however, the ED was significantly higher in the cryptorchidism patients (p=0.000). At the median follow-up of 16.3 years, 15.5% of our patients complained of moderate to severe ED. Most patients were satisfied with their overall relationship and only 34.5% were not satisfied. Anxiety, depression, and stress were more prevalent in cryptorchidism than in healthy men (anxiety: 72.4% vs. 20.7%;depression: 19.0% vs. 5.2%;stress: 60.3% vs. 10.3%;p<0.05). Additionally, ED was negatively associated with anxiety, depression, and stress symptoms (r=−0.518, p=0.000;r=−0.448, p=0.000;r=−0.591, p=0.000, respectively). Moreover, ED had a significant correlation with advancing age, psychological factors (anxiety, depression, and stress), infertility, and low levels of testosterone (p<0.05).Conclusion:Low testosterone, infertility, and psychological burden (anxiety, depression, and stress) are used as factors for predicting ED outcomes after orchidopexy for undescended testis to guide physicians to evaluate the efficacy of testosterone replacement and psychological support in their management.
