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Regulation of anti-Mullerian hormone(AMH)in males and the associations of serum AMH with the disorders of male fertility

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Asian Journal of Andrology 2019年第2期21卷 109-114页

作者： Hui-Yu Xu Hong-Xian Zhang Zhen Xiao Jie Qiao Rong Li Center for Reproductive Medicine Department of Obstetrics and GynecologyPeking University Third HospitalBeijing 100191China Key Laboratory of Assisted Reproduction Ministry of EducationBeijing 100191China National Clinical Research Center for Obstetrics and Gynecology Beijing 100191China Beijing Key Laboratory of Reproductive Endocrinology and Assisted Reproductive Technology Beijing 100191China Department of Urology Peking University Third HospitalBeijing 100191China Department of Reproductive Endocrinology Zhejiang Provincial People's HospitalHangzhou Medical CollegeHangzhou 310014China

Anti-Mullerian hormone(AMH)is a functional marker of fetal Sertoli cells.The germ cell number in adults depends on the number of Sertoli cells produced duri ng peri natal development.Rece ntly,AMH has received increasi ng attenti on in research of disorders related to male fertility.This paper reviews and summarizes the articles on the regulation of AMH in males and the serum levels of AMH in male fertility-related disorders.We have determined that follicle-stimulating hormone(FSH)promotes AMH transcription in the absenee of androgen signaling.Testosterone inhibits the transcriptional activation of AMH.The undetectable levels of serum AMH and testosterone levels indicate a lack of functional testicular tissue,for example,that in patients with anorchia or severe Klinefelter syndrome suffering from impaired spermatogenesis.The normal serum testosterone level and undetectable AMH are highly suggestive of persistent Mullerian duct syndrome(PMDS),combined with clinical manifestations.The levels of both AMH and testosterone are always subnormal in patients with mixed disorders of sex development(DSD).Mixed DSD is an early-onset complete type of disorder with fetal hypogonadism resulting from the dysfunction of both Leydig and Sertoli cells.Serum AMH levels are varying in patients with male fertility-related disorders,in cludi ng pubertal delay,severe con genital hypog on adotropic hypogonadism,nonobstructive azoospermia,Klinefelter syndrome,varicocele,McCune-Albright syndrome,and male senescence.

关键词： anti-Mullerian hormone disorders related to male fertility follicle-stimulating hormone testosterone

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Novel DPY19L2 variants in globozoospermic patients and the overcoming this male infertility

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Asian Journal of Andrology 2019年第2期21卷 183-189页

作者： Yong-Liang Shang Fu-Xi Zhu Jie Yan Liang Chen Wen-Hao Tang Sai Xiao Wei-Ke Mo Zhi-Guo Zhang Xiao-Jin He Jie Qiao Yun-Xia Cao Wei Li State Key Laboratory of Stem Cell and Reproductive Biology Institute of ZoologyChinese Academy of SciencesBeijing 100101China University of Chinese Academy of Sciences Beijing 100049China Reproductive Medicine Center Department of Obstetrics and GynecologyThe First Affiliated Hospital of Anhui Medical UniversityHefei 230022China Anhui Province Key Laboratory of Reproductive Health and Genetics Anhui Medical UniversityHefei 230022China Beijing Key Laboratory of Reproductive Endocrinology and Assisted Reproductive Technology Center for Reproductive MedicineDepartment of Obstetrics and GynecologyPeking University Third HospitalBeijing 100191China Medical Center of Reproductive and Genetics Peking University First HospitalBeijing 100034China Digital China Health Technologies Co. Ltd.Beijing 100080China Anhui Provincial Engineering Technology Research Center for Biopreservation and Artificial Organs Hefei 230022China

Globozoospermia has been reported to be a rare but severe causation of male infertility,which results from the failure of acrosome biogenesis and sperm head shaping.Variants of dpy-19-like 2(DPY19L2)are highly related to globozoospermia,but related investigations have been mainly performed in patients from Western countries.Here,we performed a screening of DPY19L2 variants in a cohort of Chinese globozoospermic patients and found that five of nine patients carried DPY19L2 deletions and the other four patients contained novel DPY19L2 point mutations,as revealed by whole-exome sequencing.Patient 3(P3)contained a heterozygous variant(c.2126+5G>A),P6 contained a homozygous nonsense mutation(c.1720C>T,p.Arg574*),P8 contained compound heterozygous variants(c.H82-1184delATCf p.Leu394_Ser395deIinsPhe;c.368A>T,p.Hisl23Arg),and P9 contained a heterozygous variant(c.H82-1184delATCTTI frameshift).We also reported intracytoplasmic sperm injection(ICSI)outcomes in the related patients,finding that ICSI followed by assisted oocyte activation(AOA)with calcium ionophore achieved high rates of live births.In summary,the infertility of these patients results from DPY19L2 dysfunction and can be treated by ICSI together with AOA.

关键词： DPY19L2 globozoospermia male infertility point mutation whole-exome sequencing

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A pilot study of the association between genetic polymorphisms involved in estrogen signaling and infant male genital phenotypes

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Asian Journal of Andrology 2012年第5期14卷 766-772页

作者： Sheela Sathyanarayana Shanna H Swan Federico M Farin Hui-Wen Wilkerson Michael Bamshad Richard Grady Chuan Zhou Stephen M Schwartzy Department of Pediatrics University of WashingtonSeattleWA 98195USA Center for Child Health Behaviorand DevelopmentSeattle Children's Research InstituteSeattleWA 98105USA Department of Preventive Medicine Mount Sinai School of MedicineNew YorkNY 10029USA Department of Environmental and Occupational Health Sciences University of WashingtonSeattleWA 98195USA Department of Genome Sciences University of WashingtonSeattleWA 98195USA Division of Pediatric Urology Seattle Children's HospitalSeattleWA 98105USA Department of Epidemiology University of WashingtonSeattleWA 98195USA Epidemiology Program Fred Hutchinson Cancer Research CenterSeattleWA 98109USA

Single nucleotide polymorphisms （SNPs） in genes that influence development of the male reproductive tract have been associated with male genitourinary abnormalities. However, no studies have tested the relationship between SNPs and intermediate phenotypes such as anogenital distance （AGD）, anoscrotal distance （ASD） and penile width （PW）. We tested whether 24 common SNPs in eight genes that influence male genital development were associated with intermediate phenotypes in 106 healthy male infants from the Study for Future Families. We used DNA from buccal smears and linear regression models to assess the relationship between anogenital measurements and SNP genotypes with adjustment for covariates. We found that the rs2077647 G allele, located in the coding region of estrogen receptor alpha （ESR1）, was associated with a shorter AGD （P=0.02; -7.3 mm, 95% confidence interval （CI）： -11.6 to -3.1）, and the rs10475 T allele, located in the 3＇ untranslated region of activating transcription factor 3 （ATF3）, was associated with a shorter ASD （-4.3 mm, 95% Ch -7.2 to -1.4）, although this result was not significant （P=0.07） after controlling for multiple comparisons. We observed no association between PW and the SNPs tested. Minor alleles for two SNPs in genes that regulate estrogen signaling during male genital development were associated with AGD and ASD, although the significance of the association was marginal. Our findings suggest that AGD and ASD are influenced by heritable factors in genes known to be associated with frank male genital abnormalities such as hvpospadias and crvotorchidism.

关键词： gene hypospadias male phenotype polymorphism reproductive

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Novel mutations in ubiquitin-specific protease 26 gene might cause spermatogenesis impairment and male infertility

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Asian Journal of Andrology 2007年第6期9卷 809-814页

作者： Jie Zhang Shu-Dong Qiu Sheng-Bin Li Dang-Xia Zhou Hong Tian Yong-Wei Huo Ling Ge Qiu-Yang Zhang Department of Anatomy Histology and Embryology Research Center of Reproductive Medicine Department of Forensic Medicine Department of Pathology Medical College of Xi＇ an Jiaotong University Xi＇ an 710061 China

Aim： To study the incidence of single nucleotide polymorphisms in ubiquitin-specific protease 26 （USP26） gene and its involvement in idiopathic male infertility in China. Methods： Routine semen analysis was performed. Infertility factors such as immunological, infectious and biochemical disorders were examined to select patients with idiopathic infertility. DNA was isolated from peripheral blood of the selected patients and control population, which were examined for mutations using polymerase chain reaction-single strand conformation polymorphism analysis. Furthermore, nucleotide sequences were sequenced in some patients and controls. Results： Of 41 infertile men, 9 （22.0%, P = 0.01） had changes in USP26 gene on the X chromosome. A compound mutation （364insACA; 460G→A） was detected in 8 patients （19.5%, P = 0.01） and a 1044T→A substitution was found in 1 patient （2.4%, P 〉 0.05）. All three variations led to changes in the coding amino acids. Two substitutions predict some changes： 460G→ A changes a valine into an isoleucine, and 1044T → A substitutes a leucine for a phenylalanine. Another insertion of three nucleotides ACA causes an insertion of threonine. No other changes were found in the remaining patients and fertile controls. Conclusion： The USP26 gene might be of importance in male reproduction. Mutations in this gene might be associated with male infertility, and might negatively affect testicular function. Further research on this issue is in progress.

关键词： male infertility deubiquitination enzymes ubiquitin-specific protease 26

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Predictive and Prognostic Value of High-density Lipoprotein Cholesterol in Young male Patients with Acute Myocardial Infarction

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Chinese Medical Journal 2017年第1期130卷 77-82页

作者： Zhao Li Ji Huang Nan Li Department of Cardiology Beijing Anzhen Hospital Capital University of Medical Sciences Beijing 100029 China

Background： The level of high-density lipoprotein cholesterol （HDL-C） is an important risk indicator and used in risk factor counting and quantitative risk assessment; however, the effect of HDL-C in young male patients with acute myocardial infarction （AMI） is unclear. The aim of this study was to investigate the effect of HDL-C in young male patients. Methods： We recruited 267 consecutive young male patients （≤44 years） diagnosed with AMI. Other 247 participants free from coronary heart disease were enrolled as controls. HDL-C levels of AMI patients and controls were evaluated to analyze the predictive value on AMI. According to the cutoff point of 1.04 mmol/L HDL-C, patients of AMI were divided into two subgroups （normal HDL-C group and low HDL-C group） and were followed up for 2 years. Clinical end points included all major adverse coronary events （MACEs）： the main cause of death, nonfatal myocardial infarction, readmissions for acute coronary syndrome, arrhythmias, or revascularization. The prognostic value of HDL-C was evaluated using Cox regression according to MACE. Results： Patients of AMI had decreased proportion in normal HDL-C group compared to controls （47.2% vs. 57.9%; P = 0.017）. Logistic regression analysis showed that there was an inverse relationship between HDL-C and AMI in young males. In the low HDL-C subgroup of AMI patients （n = 141）, 34 （24.1%） patients experienced a MACE during the 2-year follow-up, compared with 15 （11.9%） patients in normal HDL-C subgroup （n = 126）. The Cox regression analysis showed that HDL-C was an independent predictor of a MACE during the follow-up period （hazard ratio = 0.354, P = 0.006）. Conclusion： HDL-C was an important parameter for predicting the risk and the clinical outcomes of AMI in young male patients.

关键词： Acute Myocardial Infarction High-density Lipoprotein Cholesterol male Prognosis

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Anti-inflammatory effects of Eucommia ulmoides Oliv. male flower extract on lipopolysaccharide-induced inflammation

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Chinese Medical Journal 2019年第3期132卷 319-328页

作者： Jian-Ying Wang Xiao-Jun Chen Lei Zhang Ying-Yi Pan Zu-Xi Gu Ying Yuan Shanghai Innovation Center of Health Service Shanghai University of Traditional Chinese MedicineShanghai 201203China Institute of Interdisciplinary Medicine Shanghai University of Traditional Chinese MedicineShanghai 201203China School of Pharmacy Shanghai University of Traditional Chinese MedicineShanghai 201203China Science and Technology Experiment Center Shanghai University of Traditional Chinese MedicineShanghai 201203China

Background:Eucommia ulmoides Oliv. is a medicinal plant native to China, with its bark (Eucommiae Cortex) traditionally being used for medicinal purposes. Previous research has shown that Eucommia male flowers can exert anti-inflammatory, analgesic, antibacterial, and other pharmacological effects, including immune regulation. This study explored the anti-inflammatory effects of the 70% ethanol extract of male flowers (EF) of E. ulmoides in lipopolysaccharide (LPS)-stimulated RAW 264.7 cells and LPS-administered mice.Methods:Cytotoxicity of EF for RAW 264.7 cells was investigated using Cell Counting Kit-8. The production of proinflammatory mediators, nitric oxide (NO), tumor necrosis factor (TNF)-α, interleukin (IL)-1β, and IL-6 was determined using enzyme-linked immunosorbent assays. IL-17, IL-23, and IL-10 mRNA levels were determined using quantitative real-time polymerase chain reaction. Activation of the nuclear factor (NF)-κB pathway in RAW 264.7 cells was investigated via Western blotting. In vivo antiinflammatory effects of EF were studied in an LPS-induced acute inflammation mouse model by analyzing lung tissue histopathology, serum TNF-α and IL-6 levels, and myeloperoxidase (MPO) activity in lung tissue.Results:EF showed no significant cytotoxicity at concentrations from 10 to 60 μg/mL (cell viability > 80%) in the CCK-8 cell viability assay. EF inhibited the RAW 264.7 cell proliferation (EF 60 μg/mL, 120 μg/mL, and 250 μg/mL vs. negative control: 87.31±2.39% vs. 100.00±2.50%, P=0.001;79.01±2.56 vs. 100.00±2.50%, P<0.001;and 64.83±2.50 vs. 100.00±2.50%, P<0.001), suppressed NO (EF 20 μg/mL and 30 μg/mL vs. LPS only, 288.81±38.01 vs. 447.68±19.07 μmol/L, P=0.004;and 158.80±45.14 vs. 447.68±19.07 μmol/L, P<0.001), TNF-α (LPS+EF vs. LPS only, 210.20±13.85 vs. 577.70±5.35 pg/mL, P<0.001), IL-1β (LPS+EF vs. LPS only, 193.30±10.80 vs. 411.03±42.28 pg/mL, P<0.001), and IL-6 (LPS+EF vs. LPS only, 149.67±11.60 vs. 524.80±6.24 pg/mL, P<0.001) secretion, and downregulated the mRNA expression of IL-17 (LPS+EF vs. LP

关键词： Eucommia ulmoides Oliv. male flower Lipopolysaccharide Inflammation Cytokine Nuclear factor-κB

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Premature ejaculation:an update on definition and pathophysiology

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Asian Journal of Andrology 2019年第5期21卷 425-432页

作者： Mohammed Abu El-Hamd Ramadan Saleh Ahmad Majzoub department of Dermatology Venereology and AndrologyFaculty of MedicineSohag UniversitySohag 82749Egypt Department of Urology Hamad Medical Corporation and Weill Cornell Medicine-QatarDoha 00974Qatar

Premature ejaculation(PE)is the most comm on male sexual dysfunction,which represents a diag no stic as well as a therapeutic challenge for physicians.However,no universally accepted definition is currently available for PE.As a result,physicians continue to diagnose patients with PE according to major guidelines set by the professional societies.These guidelines either recommend the use of validated questionnaires or patient-reported outcomes.Recent efforts directed toward classifying PE may help provide a better understanding of the prevalence and risk factors of this disorder.While the exact etiology of PE has not been clearly elucidated,several risk factors have been strongly reported in the literature.Clearly,to understand the revised definition of PE,its etiology and pathophysiology is necessary to improve the clinical management of this medical condition and form the basis of future research in this regard.In this review,we highlight the past and current definitions of PE and present an appraisal on the classifications and theories suggested for the etiopathogenesis of PE.

关键词： ejaculatory disorders male sexual dysfunction premature ejaculation

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Anti-diabetic activity of quercetin extracted from Phyllanthus emblica L.fruit: In silico and in vivo approaches

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Journal of Pharmaceutical Analysis 2018年第2期8卷 109-118页

作者： Prabhu Srinivasan S.Vijayakumar Swaminathan Kothandaraman Manogar Palani Computational Phytochemistry Lab PG and Research Department of Botany and Microbiology A. V. V. M Sri Pushpam College (Autonomous) Department of Physics RKM Vivekananda College (Autonomous)

In this study, molecular interactions of the ligands, quercetin, gallic acid, and metformin with various diabetes mellitus-related protein targets, such as glycogen phosphorylase and peroxisome proliferatoractivated receptor gamma, were assessed. It was revealed that quercetin possesses good binding affinity to both targets. Quercetin is a major constituent of methanolic extracts of Phyllanthus emblica fruit. The antihyperglycemic effect of quercetin in streptozotocin(STZ)-induced diabetic rats was examined. The isolated quercetin administered at a dose of 75 mg/kg body weight produced a maximum decrease of14.78% in blood glucose levels in the diabetic rats after 7 days of treatment. Furthermore, quercetin doses of 50 and 75 mg/kg were shown to significantly improve the profiles of triglycerides, high-density lipoprotein, very-low-density lipoprotein, low-density lipoprotein, and total cholesterol at the end of the study in STZ-induced diabetic rats. The administration of quercetin(25, 50, and 75 mg/kg body weight)daily for 28 days in STZ-induced diabetic rats resulted in a significant decrease in blood glucose and urine sugar levels, with a considerable rise in plasma insulin and hemoglobin levels. Therefore, quercetin is a potential drug with antidiabetic and antihyperglycemic action mediated by changes in the levels of glucose, cholesterol, and triglycerides as indicated by in silico and in vivo studies.

关键词： Bioactive molecules Glycogen phosphorylase Molecular docking Phyllanthus emblica Quercetin Albino Wister male rats

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Ploidy-, gender-, and dose-dependent alteration of selected biomarkers in Clarias gariepinus treated with benzo[a]pyrene

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Journal of Environmental Sciences 2015年第12期27卷 95-102页

作者： Ali Karami Swee J.Teh Mohamad Pauzi Zakaria Simon C.Courtenay Laboratory of Aquatic Toxicology Faculty of Medicine and Health SciencesUniversiti Putra Malaysia School of Veterinary Medicine Department of AnatomyPhysiologyand Cell BiologyUniversity of California Centre of Excellence for Environmental Forensics Faculty of Environmental StudiesUniversiti Putra Malaysia Department of Environment and Resource Studies Canadian Water NetworkCanadian Rivers InstituteUniversity of Waterloo

Naturally-occurring and artificially-induced polyploids have been documented in various fish species but to date no comparison has been reported of the impacts of ploidy on fish biomarker responses to organic pollutants.This study describes effects of ploidy,gender,and dose on biliary fluorescent aromatic compound（FAC） concentrations,hepatic ethoxyresorufin-O-deethylase（EROD） and glutathione S-transferase（GST） activities in one of the most commonly cultured warm-water species,the African catfish Clarias gariepinus.Recently matured male and female diploid and triploid fish were intraperitoneally（i.p.）injected with 0,5 or 25 mg/kg benzo[a]pyrene（BaP） and liver and gallbladder were sampled48 hr later.No significant differences were found between ploidies in bile concentrations of7,8 dihydrodiolbenzo[a]pyrene（7,8D BaP）,1-hydroxybenzo[a]pyrene（1-OH BaP） or3-hydroxybenzo[a]pyrene（3-OH BaP）.However,concentrations of the biliary FACs did differ between males and females at different dose of injection with generally higher concentrations in females at the low dose of BaP and higher concentrations in males at the higher BaP concentration.Hepatic EROD activity did not exhibit gender-dependent difference,whereas it was significantly higher in triploids than diploids.GST activities were not significantly influenced by any of the tested factors.This work advanced our understanding of the role of ploidy,gender,and dose in biotransformation of pollutants in fish.

关键词： Triploid Diploid male Female Fish biomarkers

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46 XX karyotype during male fertility evaluation; case series and literature review

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Asian Journal of Andrology 2017年第2期19卷 168-172页

作者： Ahmad Majzoub Mohamed Arafa Christopher Starks Haitham Elbardisi Sami A1 Said Edmund Sabanegh Jr Cleveland Clinic Foundation Department of Urology Cleveland Ohio USA Hamad Medical Corporation Department of Urology Qatar Cairo University Department of Andrology Giza Egypt Reston Hospital Department of Urology Virginia USA

Forty-six XX disorder of sex development is an uncommon medical condition observed at times during the evaluation of a man＇s fertility. The following is a case series and literature review of phenotypically normal men diagnosed with this karyotype. Our goal is to comprehend the patients＇ clinical presentation as well as their laboratory results aiming to explore options available for their management. A formal literature review through PubMed and MEDLINE databases was performed using ＂46 XX man＂ as a word search. A total of 55 patients, including those conveyed in this article were diagnosed with a 46 XX karyotype during their fertility evaluation. The patients＇ mean age _＋ s.d. was 34 ＋ 10 years and their mean height ＋ s.d. was 166 ＋ 6.5 cm. Overall, they presented with hypergonadotropic hypogonadism. Sexual dysfunction, reduced hair distribution, and gynecomastia were reported in 20% （4120）, 25.8% （8/31）, and 42% （13131） of the patients, respectively. The SRYgene was detected in 36 （83.7%） and was absent in the remaining seven （16.3%） patients. We found that a multidisciplinary approach to management is preferred in 46 XX patients. Screening for remnants of the mullerian ducts and for malignant transformation in dysgenetic gonads is imperative. Hypogonadism should be addressed, while fertility options are in vitro fertilization with donor sperm or adoption.

关键词： hypogonadism infertility male sex-determining region XX disorders of sex development

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